Improving the prevention and management of cryptococcal meningitis in HIV-infected persons in Africa
- Impact Case Studies
4 December 2020
Cryptococcal meningitis (CM) is a serious opportunistic infection of advanced stages of HIV-infection.
Until recently, it was responsible for over 500,000 deaths per year. Today, despite the high coverage of HIV treatment services, it is still responsible for about 150,000 deaths annually. LSTM staff have, in a partnership with other UK institutions, played a leading role in five pivotal trials that have been conducted in multiple countries sub Saharan Africa and in Vietnam. These trials have generated clear, policy-relevant knowledge on how mortality from CM can be prevented. Novel biomedical strategies have been demonstrated for the prevention and management of CM. This has informed international guidelines issued by the WHO and has changed national policy and practice in countries including South Africa, Tanzania, Uganda, Malawi and Zambia. Adoption of these guidelines has, in turn, saved tens of thousands of lives across low-resource settings.
Professor Shabbar Jaffar
Professor Shabbar Jaffar, Head of Department: International Public Health and Professor of Epidemiology talks about the impact of the research on cryptococcal meningitis infections and its influence on policymaking decisions.
Sabitha I’m an epidemiologist here at
the Liverpool School of Tropical
Medicine the problem we were addressing
is a mortality from HIV infection was
very high it was particularly high in
people who either present with late
stage HIV infection or who failed on
antiretroviral therapy in those people
the one of the commonest ways that they
died was from cryptococcal meningitis
the problem was was that the treatments
for cryptococcal meningitis were not
available easily in Africa our research
has looked at new ways of treating
cryptococcal meningitis the different
stages of cryptococcal meningitis and
we’ve identified simple practical
regimens that are as effective if not
more effective than the than the older
older ways of treating cryptococcal
meningitis our research has informed
several World Health Organization
guidelines
most recently the the actor trial that
identified a simple regimen for the
management of cryptococcal meningitis so
essentially that led simpler regimens
that can now be accessible to people
living with HIV infection in many parts
of Africa in areas where they couldn’t
get the previous gold standard which
which which involved complex into the
intravenous treatment
so with these simpler more practical
regimens we anticipate that access to
treatment for cryptococcal meningitis
will will increase and thereby it will
reduce mortality substantially across
Reducing HIV-associated mortality in sub Saharan Africa by improving the prevention and management of cryptococcal meningitis
Cryptococcal meningitis is an opportunistic fungal infection that occurs in the advanced stages of HIV infection and is responsible for 15-20% of AIDS-related deaths.
LSTM has played a leading role in pivotal trials that have evaluated novel approaches for the prevention and management of cryptococcal meningitis in low-resource settings. Together with our partners, we have identified novel biomedical treatment and prevention strategies that are practical, low-cost and effective, which have been incorporated into World Health Organisation guidelines and led to changes in clinical practice in Africa. The research findings stimulated donor investment to support low-resource settings to scale up the approaches, including investment in a generic version of a key drug (flucytosine).
good afternoon everyone and welcome to another exciting lstm launch time seminar
on reducing hiv-associated mortality in sub-saharan africa by improving
the prevention and management of cryptococcal meningitis we have today with us some four
outstanding researchers and eloquent speakers all have very impressive
knock-out collaborations and i’ll just um you’ve seen you know their bio in an invitation but i’ll just do a quick
um introduction so starting with um professor shaba jafar he’s head of department um
iph here he’s an epidemiologist and clinical trialist and his what in hiv since um the mid and
90s he uh his focus is on population-based and clinical research on the prevention
of hiv associated mortality our next speaker
is um the director of the school of football medicine professor david lalu
he’s a professor of tropical medicine and his research is focused on clinical trials particularly hiv-related
infections malaria and vitamin um ted speaker will be professor tom
harrison professor of infectious diseases saint george’s university of london he’s
deputy director of the institute of infection and immunology and lead for the center of global health
and he also has you know clinical roles within the nhs our last speaker
is professor suyuki who is the chief scientist at the
national institute for medical research in tanzania is also honorary global health professor
at lstm his research to date has really focused around the control of hiv
and tobacco losses in east africa um so we’re hoping that you know all the
speakers will speak for around about time 40 minutes and then we’ll have enough time for questions and answers
now um in in the chat box you know this is a specific chat for questions and answers
please keep your questions coming and i will you know um quality uh questions and prioritize them
and we hope to be able to put the questions to the speakers after all the presentations
so the running order will be uh we’ll start with professor shaba and
then to david um tom and the last speaker will be professor in fernando
so now over to shabbat to start to start us off thank you okay thank you very much so
we’re going to present about 20 years of work in hiv infection
and cryptococcal meningitis to you before we begin just to make clear these
are this work is very much a team effort with large teams in europe in the uk
and in different countries in africa and in vietnam
so just to remind you of the of the hiv
epidemic very devastating impact it’s had to date now
there’s been 40 million cumulative deaths and there are 38 million people
living with hiv infection cryptococcal meningitis is a late stage
hiv infection uh so hiv infection uh in the absence of treatment um
it it people live for about 10 years and cryptococcal meningitis occurs
at the end of that period when the immune system is depleted uh people typically will have cd4 counts
below 100. so the the the burden from cryptococcal
meningitis has been very high particularly in africa and here i i’ve only
given the african uh data from hiv and from uh cryptococcal meningitis so
in hiv we are now seeing about seven hundred thousand deaths a year in
sub-saharan africa in meningitis death rates were
very high they’ve come down because of the scale-up of antiretroviral therapy
but they’re still at 135 000 deaths a year so a phenomenal
death burden from this infection which actually many people thought would go
away with the scale up of antiretroviral therapy of course that hasn’t happened and it
isn’t going to happen and the way cryptococcal meningitis occurs
is it occurs in those people who delay their antiretroviral therapy in
other words present late or they actually fail on antiretroviral therapy
and these days we’re seeing very large numbers of people who have been on antiretroviral therapy
failing and acquiring cryptococcal meningitis
now the median survival from cryptococcal meningitis this is uh in the pre-antiretroviral therapy era
was actually weeks to months but today of course if you can treat the cryptococcal
meningitis if you can get them over that episode then patients have the opportunity to live
for decades after that if they get onto uh antiretroviral therapy and that
is available widely in africa uh on on the right is a picture of uh stephen
watiki he’s a patient on one of our steering committees actually for studies in diabetes and
hypertension um he developed hiv in around 1984 1985 86
and survived through to 2006 um but with a lot of problems from hiv
and then from 2003 has been on antiretroviral therapy and has been very
very stable now during that time during that early time just after he got hiv infection uh he actually
uh has had five episodes of tuberculosis one of which was mdr uh one episode of
cryptococcal meningitis and also kaposi’s sarcoma he overcame
all of those uh i struggled but once you get once you treat the
cryptococcal meningitis the life expectancy after that is is a lot longer now with the
cryptococcal meningitis it you can detect it in the blood initially once the cd4 count has fallen
very low and then from the blood it moves to the brain and becomes a meningitis and that’s when
it becomes very very problematic so but in in both of these stages either in the
in the in in the blood stage or in the uh when when it’s become a meningitis
it hasn’t been very clear exactly how you treat it and the treatments that
we had been using um were complex expensive
difficult to administer and actually often unavailable in the case of the
meningitis it needed and still does need intravenous treatment and so that’s going to be the
subject of our talks uh initially uh started uh with trials that were done uh
uh in vietnam by david and colleagues looking at combination uh anti-fungal therapy for the
management of of cryptococcal meningitis once it’s become a meningitis and then um
then we will present the the data from uh sub-saharan africa uh which looks at
um uh evaluating antifungal combinations in in uh uh in in africa
so both of these studies both of these sets of studies look at
the management once cryptococcal meningitis has has developed and then the last set of studies which
will be uh which uh fernando will present on uh looks at uh the the the what you do
with the cryptococcal meningitis or the cryptococcus when you detect it in the blood so those studies were done in tanzania
and zambia and fernando will present on those so i’m gonna hand over now to
today yeah thanks sharma um and and i think uh what i really want to do is it’s just
introduce this concept of treatment of cryptococcal meningitis um worth also reflecting that
cryptococca meningitis has come to prominence very much in the last 20 years after 25 years because of the hiv
epidemic but it has been around for a long time and i was first undertook cryptococcal meningitis
research in 1989 in papua new guinea when i went out there and found many cases
and at that point it was actually affecting patients within a normal immune system and and even at that time
people were struggling to think through how you best treated uh this this very
unpleasant and very distressing disease amphotericin is a drug that’s been
around since the the mid-1950s and one was you being used in various in
various ways and liking so much of infectious diseases increasingly people are
thinking about the use of combination therapy we we now understand that for many infections
such as tb such as hiv the combination of several different agents gives you the best chance of improving
of getting rid of a bug whatever it happens to be and improving outcomes and so combination therapy
was starting to be thought through and so we in vietnam actually conceived in the
early 2000s but took some time to get off the ground undertook the first
trial of combination therapy to look at whether that would improve mortality in hiv-infected individuals
and that was based entirely in vietnam in a collaboration with the oxford unit
there and essentially just a randomized individuals to one of three regimens
amphotericin in combination with flu cytosine that’s again another old antifungal developed
in around 1957. uh amphotericin uh with fluconazole a neuroazole drug
uh that was being thought about for the for the management of cryptococcus meningitis and then amphotericin alone and we also
used a higher dose that had been used previously to to try and evaluate what the best regimen was and if you
could push on to the next slide please shabba really what this study showed for the
first time was that when you use amphotericin and flu cytosine in combination
and compared it to amphotericin alone both at day 14 and day 70 there was a clear evidence of
mortality benefits now you can see that the confidence intervals are quite wide around those estimations uh because it
was relatively small trial done on a relatively small budget but it was a very clear signal that
there was there was a mortality benefit you can see also there on the capitol maya plot that the amphitheatres and
fluconazole the new azole drug or the azole drug was intermediate
and we really didn’t have power to to demonstrate uh whether amphitheaters and flucytazine uh
was definitely better than amphotericin and fluconazole although many of the secondary endpoints suggested that that were the case
and certainly if you went out to much longer up to six months in the trial uh there
was some significance albeit in the second endpoint so at that point we had some evidence that
amphotericin and flu cytosine uh given uh for two weeks two weeks found for terrorism
uh was was the best regimen but i think worth highlighting at that point at this point that the
challenges of giving a two-week infusion in a resource-poor setting when there
are very few uh nursing staff around and this is associated with a with a fair degree of
toxic effects as i’m sure tom will come on to was a real challenge so we knew what the best regimen was
but it was difficult to give and through cytosine the other agent again should be very cheap and very
easily available but was a real problem to get through most of the tropics and so actually practically despite that
evidence what we saw around the world was was people using fluconazole on its own
the other aspect and we’re predominantly going to talk about managing the fungal uh the the the fungal
infection today and i think it’s worth saying from this study also uh we were able to show that the the combination uh
got rid of the fungus in the csf much more rapidly uh than advertising alone but i think it’s also important although
we’ll focus on antifungal therapy uh today it’s also important to recognize there are other aspects of the disease that
are problematic and in particular the fungal infection causes a really brisk inflammatory
response in some patients and that’s associated with very high intercranial pressures
so the pressure within the cranial cavity goes up and for some people that may well be it’s both distressing but also may be
the cause of death so one of the other studies that we then thought about was to look at how we might dampen down that
inflammatory reaction and potentially also reduce intracranial pressure
dexamethasone is a broad steroid that’s been used in a number of different
different infections and in particular particularly in a number of brain infections and
dexamethasone for example is well established to improve the outcome in pneumococcal meningitis
so there was there was a reasonable um the hope that we could actually see some some improved outcome but of course
against that uh we were worried that that flu that um that text of metastasis may reduce the rapid clearance of our
fungus and so there was genuine equipoise in this study and we went on to
two arms as you can see there uh basically either patients giving standard
treatment a combination therapy but they’re also giving dexamethasone for six weeks or given a placebo for six
weeks and if we can move on to the next slide please shabba unfortunately this clearly showed that
dexamethasone uh was harmful here so you have the kaplan
kaplan plot there um and you can see in the lighter gray that is the
dexamethasone and on the axis there that’s survival so fewer people survived
with dexamethasone than they did with placebo although you can see um from the mortality figures just below
there that wasn’t statistically significant but it was a really a really concerning signal
that mortality was higher with the dexamethasone what was clear and what eventually
stopped the trial earlier uh was that that there were very poor outcomes or there were poor outcomes in
terms of disability um at ten weeks and again you can see uh that the difference there was a large
ratio of 0.42 so this trial was actually stopped earlier uh than wandering planned
uh because of a signal that showed that dexter medicine wasn’t helpful and i think uh
it’s fair to say that we are still struggling to think about other adjunctive therapies within this
disease in addition to anti-fungal therapy and i think over the next few years that’s in addition to improving
anti-fungal therapy is an area we need to think much more clearly about and i’ll now pass over over to tom thanks
thank you very much uh david and i’m very happy to continue the story now
and take the focus to africa and the actor trial and obviously as shabbos already
emphasizes these types of this type of work is very much a team effort and i’m presenting on behalf of
the whole actor team and just to give you a feel for the team this is a picture
of our last investigators meeting when we actually unblinded the results in 2017
and if any of the listeners if you want to look at the original presentation of the results in
2017 i’ve given you the link there but of course it’s not just the
principal investigators it’s also the result of a huge amount of work by
a very many people at all the sites involved in the study nurses and coordinators and study
doctors and and everyone so this was the plan of my uh section i want to tell you about the
actor trial how this took the story of treatment forward from what david has described the rationale
for the study in the results and then talk about the impact of the trial on guidelines on access to
this drug flucide scene that david’s mentioned and then the cost effectiveness work
led from liverpool that’s very much aided the ongoing implementation of the
results and then if there’s time just a couple of slides to mention our ongoing collaborative work
so um i mean i think shabbat and david have already kind of spoken to this to this
problem of treatment and at the point i want to make about the act of trial was it was actually based on
a number of phase two studies that took place over a number of years um prior to the phase three actor trial
and in these phase two studies we we were aiming to try and define regimens
that could be more feasibly implemented and would be safer than this accepted international
standard of two weeks amphitheaters and b and flucidazine which which was simply not really
feasible or available in most african centers certainly but on the other hand would be more effective than fluconazole which david
has mentioned is the has been and still is a commonly used treatment for this disease in
africa but which unfortunately is just as i’ll show you a much less strong drug and one with when this is used in
treatment in fact the survival of patients is is less than a quarter of after one year of follow-up so just to
reiterate some of the challenges of two weeks of amphotericin b deoxycolate in resource limited settings
it frequently causes thrombophlebitis and that not uncommonly leads to
life-threatening sepsis bacteremia and then in addition there’s a
dose-dependent renal impairment there’s electrolyte wasting so patients can get life-threatening
hypokalemia and hypomagnesemia if it’s if the if these electrolytes are
not carefully monitored and managed but and in addition what sometimes not recognize is
really a very significant drop in hemoglobin anemia which over 14 days of treatment the
average drop in hemoglobin is over two grams of of hemoglobin on the other side of
the story this is the data when fluconazole is used as treatment and this comes from a
careful cohort study from the mlwu unit in blanter as i’ve said showing
that this drug is actually just as i’ll show you later just simply less effective in controlling the
organism such that patients keep on dying and the survival rate is very low after a year so the approach in the
phase two studies that led up to the acta trial was to try and define uh regimens that would be more effective
than fluconazole but sustainable in africa and based these studies on this
early fungicidal activity which was an endpoint we first developed in thailand published
as mentioned then the lancet in 2004 and this was looking at the rate of clearance of infection
over the first 14 days of treatment and on the y-axis of these graphs you have the colony-forming units of
cryptococcus per mil of csf which is derived from doing serial lumbar punctures on these
patients when we first applied this technique in africa this was just an observational study
small number of patients in cape town we immediately saw and understood why the fluconazole results were so
disappointing because with the dose that was used routinely at that time 400 milligrams a day
this drug was simply not controlling the infection nothing like compared to the activity
with amphotericin b as shown on the right so subsequently we in in studies in uganda
in fact we we looked at doubling or tripling the dose of fluconazole and we did see a dose response effect with more
effective control of infection and we had no toxicity uh signal
but still the rate of clearance wasn’t that uh that we’d seen with amphotericin b so
subsequently in a randomized study in in malawi we looked at an oral combination of
high-dose fluconazole plus the flu cytosine again an oral drug option and now we did see
clearance that approached what we’d previously measured with amphotericin b and in addition we saw
that the survival of the patients perhaps not surprisingly looked better with the combination almost statistically significantly
better even though this was a small phase two study not powered for mortality endpoint
so that was one of the experimental strategies that we took forward to the actor’s trial
high-dose fluconazole plus flucide scene as an oral combination the other uh experimental strategy we
tested in actor was giving a shorter course of amphotericin b just one week instead of the two weeks
and this was based on the fact that we know this drug has a very long half-life it particularly in brain tissue and we
know that the side effects become particularly significant during the second week of treatment so we thought we could get most of the
efficacy and much less of the toxicity if we just gave one week and this was a phase two
cohort study again in uganda where actually we just gave five days of amphotericin b
and the point i want to make is that with this we saw very good rate of clearance of infection but it
didn’t slow down in the second week even though we’d stop dosing the drug after five days
probably because as i’ve said the very long half-life of this drug and supporting the concept that we could
get most of the efficacy with a shorter induction course and actually that was also backed up by
careful animal model work that incidentally was also done in liverpool in william hope’s laboratory careful studies in the
mouse and the rabbit model of cryptococcal meningitis where he showed just three days of
amphotericin b therapy was equivalent to daily dosing over a whole 14 day period
in terms of the cfu counts of cryptococcus in the animal organs after the end of 14 days
so those were the two treatments experimental strategies that we took forward into acta the strategy one the this oral optimized
combination secondly the amphotericin b just but given for seven days and we compared it
against the international standard of amphotericin b uh for 14 days and in addition perhaps
we were a little greedy we asked one further question and this is relates to what david mentioned about the com
the partner drug to give with amphotericin b in the amphotericin bee arms patients
were in addition randomized to either fluconazole or to flucytazine as the partner drug
to find out hopefully once and for all which was the superior drug as a partner and then after two weeks
and all the patients get the same standard consolidation of maintenance with fluconazole
and of course antiretroviral therapy so just again to reiterate you know the logistic challenge of
conducting a multi-center study like this this was actually the largest trial to date in cryptococcal meningitis
and as a tribute to the fantastic work of the sites just four participants lost to follow-up during the study
so i’m gonna cut straight to the results because of um we haven’t got so much time but the bottom line was that all three
strategies performed very similarly so in this survival curve actually the blue is the oral combination the red
is the one week after terrorism being the green is the two-week amphotericin b so very similar no significant
difference between those strategies and you will you won’t be surprised that we easily met
our predefined criteria for non-inferiority between those strategies it was
interesting because the oral arm performed fail very well even though it did it was
associated with less rapid clearance of infection as shown here as expected however
from the phase two studies the one-week amphotericin b uh was associated with pretty much
exactly the same rate of clearance of infection as two weeks after teresa b no no difference in terms of safety
these are a very sick population of patients and there were lots of adverse events and again as expected perhaps
there was much more anemia significant anemia in terms of the proportion of patients having grade three and grade four anemia
in the two weeks amphotericin bee arms than the one week or the oral regimen
and the same trend seen in terms of the drop in hemoglobin over 14 days or the
requirement for transfusion we didn’t have any problem however with any neutropenia which is
a theoretical risk with the flu cytosine that wasn’t seen we didn’t have any problem with hypokalemia
given the careful protocols we had for measuring and monitoring potassium
there was no problem with liver function with the fluconazole but again as expected there was more renal impairment
with two weeks amphotericin b than with one week or the oral regimen finally for the partner drug comparison
there was a clear-cut answer here in favor of flucitazine as shown here on these survival curves with the flu
cycling in the red the fluconazole in the blue as partners with amphotericin b and this was
a statistically significant improvement in survival with flucide scene as a partner
and it mirrored i should say sorry it mirrored an improve an improvement in rate of
clearance of infection with flucytosin compared to fluconazole as shown here so if you broke down the
results of the trial into actually the five different drug treatments given in the trial then
the best performing arts single arm was the one weak amphiturism being flucide scene in the green at the bottom there
and then the blue is the oral combination the purple is two weeks after terrorism being flu cytosine
the brown is two weeks amphetary symbian fluconazole and the least well performing arm the red at the top was
the one week amphotericin b and fluconazole and in fact the one we came for terrorism being
fluctuating just 24 10 week mortality and that was statistically
better than the two weeks and for terrorism being flucitazine and some people said well that’s all
very well that’s ten weeks follow up what about longer so in a subset of the patients a considerable subset
in malawi we had very complete follow-up to 12 months and this graph just reiterates the continued
benefit of one week amputation being through cysteine right through to 12 months
so we felt the results of the trial reflected a balance between the effect of the drug
regimens on the rate of clearance of infection and their tolerability the one-week regimen uh was just as
rapid in clearing infection but was much better tolerated in terms of the anemia and renal impairment
and obviously the the implications of the trial potentially uh given that this regimen is more
feasible to give in in africa is a potential reduction in the mortality from cryptococcal meningitis
from around 70 percent for example in centers using fluconazole monotherapy down to the 25 to 35
range in the flue cycling containing arms in the trial and obviously that could translate
into tens of thousands of lives saved each year so we actually shared the results of the
trial before they were formally published after we presented in paris with the who they asked us for the
detailed results so that immediately after publication they could come out with revised
who guidelines for the treatment of cryptococcal meningitis and these revised guidelines recommended
the one week amphotericin b and flucidosine as the preferred regimen and the oral combination as a secondary
regimen particularly of course in it in places that couldn’t give the amphotericin b and other guidelines
have subsequently followed suit but obviously these recommendations depend absolutely
on now rapid and wide access to generic flu cytosine so in addition we shared the results
early with an organization called unitade and um and and and and others we
advocated with unitade and were successful in getting them to support a 20 million dollar program to
support the management of patients with advanced hiv disease and importantly this program
uh supported generic flu cytosine the cryptococcal action diagnostic tests
and this has been rolled out in seven i think it’s actually up to eight countries now through a large ngo called the chai
and with angel lois from our group as their consultant and more than one uh manufacturer is
committed to making the generic flu cytosine and we’re expecting uh significant uh cost savings just to
mention uh in terms of flu cycling also a recently funded project to make a
modified release of flucitazine uh which is being led by the ndi and
isabella ribera from dndi a formulation that could be given twice a day
because currently this drug actually has to be given four times a day which of course is a challenge for adherence
so it’s exciting times for implementation of the actor trial results and we’re helped
because in some settings this is actually cost saving um in south africa botswana
and zambia these are countries that before the trial uh these were using amphotericin b
for two weeks with or without fluconazole and for these countries
based on careful uh cost-effective analysis led by louis neeson’s group at the liverpool school
we were able to show that this switching to the one-week regimen would save
14 lives out of every 100 patients treated and on average 400 for each patient
treated or forty two thousand dollars per hundred patients treated so in healthy economic terms in these
settings the actor regimen would dominate it would save lives and save money in these countries
but as david mentioned as well uh and uh you know in much of africa the the
the standard treatment is fluconazole so the relevant comparison perhaps is the addition of flu cytosine to
fluconazole as tested in active versus fluconazole alone and this shows you the results of a second
uh cost-effective analysis uh done showing that the dollars the us dollars per life year
uh saved the cost per life year saved of adding flucyitis to fluconazole for
treatment of cryptococcal meningitis and it shows depending on the cost of the flucitazine
and also on the mortality with the fluconazole alone because obviously in acta we didn’t have an arm of
fluconazole alone but actually there’s good data from other cohort studies and we think we’re in the area of this
red circle and it basically works out to a mere forty dollars per life year saved
the cost of adding through cytosine to fluconazole as improved treatment so
implementation is in progress the western cape of south africa is actually the first african setting to provide flu
cycling for routine use for the treatment of cryptococcal meningitis this was in 2019
the ministry of health they’re granted a waiver on registration pending re-registration of generic flu
sightseeing by milan and then there’s been a surveillance of the rollout of this program
and i’m happy to report that the one-week amphotericine being flucitane
regimen used in south africa in routine care in the over 300 patients the in-hospital
mortality has dropped from a long-term average of 30 around 35 as shown on that
graph in the red line to 24 in the patients treated with the new regimen and that that that’s
surveillance work led by nelsh governor and colleagues from johannesburg
and then secondly professor fenanga may mention a second implementation project in
tanzania also going on in malawi and cameroon which is slightly broader
improving treatment for all hiv-related meningitis but including the updated cryptococcal treatments
and their their early results are also very very encouraging with mortality at two weeks
reduced from 20 59 to 29 so i want to finish their talking about
actor i just want to just reiterate thanks to everyone at liverpool particularly of course shabba
and david lalu professor fenanga dwala wang and his statistical team louis neeson and his
health economic team and all their teams and all the people in addition at the mlw unit in in blanta for a fantastic
collaboration i’m just happy to mention that we have ongoing collaborative projects so i hope we’ll be able to have
a another seminar in the future and we’re working together with joe jarvis at the
london school of hygiene and tropical medicine on this follow-up phase three study the ambition
study which is looking at liposomal amphotericin b against the new actor standard of one
week amphiterosyn oxycolate and that’s almost finished and the second one ongoing study just
starting is called effect and this will be looking at the oral combination as tested in acta but in the
much earlier screening setting that shabba mentioned and professor fenanga will talk about
so i will finish there and be happy to try to answer questions with the rest of the group at the end of the seminar
good afternoon ladies and gentlemen um really honored to make this presentation
on behalf of remstart encrypting the team carried out
a randomized trial to prevent immortality from cryptococcal infection
in hiv infected the people the rim study trial and an implementation
trial to scale up the intervention the rims that intervention in a really
setting routine health system the trip trial the rain start is an abbreviation of
reduction of ill mortality among hiv-infected subjects starting near erv and trip
is an abbreviation for translating research into practice which focused on
evaluating our speeding up adoption of the remstart
of the remstart package next slide please
um so our team was was from the in an
equitable partnership between the uk uk institutions
and the and the tanzanian institutions and it was based on principle of trust
in the and ecwid we had a multi-disciplinary team we had a multi-disciplinary team with
epidemiologists public health specialists economists statisticians and data and data managers
that were involved in this uh in this project and we had extensive engagement
with ministry of health including hiv control programs
and senior officers at the ministry which advised the steering and implementation team
of the remstarty and the trip and trip project we also engaged the national
and the international hiv bodies including who a consortium
for advanced hiv disease like crypto mug units aid and child
um so uh has already eluded by by professor thom crypto coco
is among the top leading cause of death in people living with hiv and therefore the our team research
questions was whether screening for cryptococcal in the blood combined with
pre-emptive treatment with fluconazole and enhancing initial adherence support
reduce all-cause mortality in asymptomatic cryptococcus positive infected individual the other question
is whether this would be a cost effective intervention and the if so
how how do we how do we how do we scale up the intervention so as to say um
we randomized almost 2000 subjects to intervention and control in in
tanzania and zambia the intervention included cryptococcal screening and
preemptive treatment with fluconazole for cryptococo positive asymptomatic
people and weekly home visits for four weeks to support adherence and as you can see
in this eye in this chat here the proportion of people
died we are less in the intervention throughout the 12 months of follow-up period
and the overall mortality was um at 30 percent lower in the intervention
as compared to to the control group so as a result of this who conducted a
systematic review for evidence and realms that it was among the two trials
that contributed to development of our whole guideline for management of
advanced hiv hiv disease so the big
question now the question where how do we scale up the rendered package in a
really life setting health system and they achieve the same impact as in in rip state trial
on mortality reduction so we designed the trip trial using the same
package the webstat package with a m-health package for adherence follow-up
and we screened it 2773
patient participants 45 subject they had really cryptococca
meningitis so we are excluded but we enrolled the 200
728 subject of which 88 subjects were crypto coco positive
was symptomatic subject and the 200 600 2648 were cracked
negative and in the defaultium we enrolled 12 hundred and 19
19 19 19 subjects and these were implemented
in 24 facilities which were randomized into early early starting
intervention in the default deferred arm as a control next slide please
so we conducted a number of stakeholders engagement and training meeting before
during the study and even after the study we started with why these stakeholder meetings including
minister of health health providers and other implementing partners
um we did this interface one where we disseminated widely the
reps that find it to make sure that the people that the partners that we are working with
understand fully the intervention and we develop the trip data tools jointly
jointly with the health providers and the other implementers to ensure
simple tools to implement in a normal health system without adding much workload to health
staff so we conducted extensive training with health workers provider including leadership of
health facilities and we empowered them to own the the
interventions rather than the researcher conducting it we provided technical support we trained
them on various study procedures including lumbar puncture
and and as you can see in this slide that is me with facility personnel my colleague
and the hospital in charge of one of the facilities that participated in in
webster and this is dr shimela shimela uh who really took the leadership of the the the
intervention in this particular site next slide please
we had number of challenges uh as shown in this slide here and we tackled these
by working through our partnership and having regular engagement with
stakeholders spending time to empower local health care providers
to to to in order to save these uh to to to to resolve these challenges
can we have a next slide please so uh this mitigation this this mitigation
intervention really i have given them as an example of result of working together with
stakeholders such as the ministry of health uh health providers in international organizations like
units aid and the international steering committee for advanced hiv disease
including also the consortium for advanced hiv disease the cryptomag and
pepper and uh to ensure and to ensure effective effective
coordination of effort among implementers and founders as well as providing a forum to
exchange ideas troubleshooting programmatic related issues and the number and number and
number of site visits in a meeting happened unit 8 for instance visited
trip sites and dream a dream this year study that tom talked about it earlier this one
focused on treatment of encephalitis in hiv individuals so
we we we had several visiting several several partners visiting our
site and in this meeting trip contributed to funders meeting in international
committees committees is an example of scaling up scaling up intervention and uh
and uh as a result of this um international meetings unit unit aid
invested u.s 20 million dollars is tom talked about this to to avert
hundreds of thousands of preventable deaths among advanced hiv disease by
making sure that um the package are accessible like medicine including full corners or
diagnostic as you saw we had challenges for cd4 but now they are providing access to
point of care cd4 testing to resolve that that challenge next slide please so this
project is implemented in seven countries in africa
including including tanzania united egg chai through international
steering committee also coordinated uh coordinated various projects project partners working on in a
advanced hiv disease including trip and together we contributed
to development of the global advanced hiv disease
toolkit the toolkit is online and can be accessed in the link provided in this
slide next slide please so as a result of this advocates by
these international bodies um the paper guideline now uh they indicate is indicating support
of cryptococcus screening and preemptive treatment and this is very
promising uh it’s very promising enabling environment for scaling up cryptococcus screening
next slide um in this slide i’m showing some results from trip
uh this it was this was mediterranean analysis but already we are we were observing we are observing the same
trend like in our previous remstat finding among cryptococcal antigen positive and
negative you see both arranged in the trip resulted in mortality reduction
and we also noted excess mortality in asymptomatic cryptococcal antigenic positive on
preemptive fluconazole therapy when compared to cryptococcal antigen
negative individuals so uh as a result as a result of all these
meetings and all these are engagement meeting and the result and the feasibility of the study
at the national level rem starting the trip contributed to updating our national guideline for management of
hiv and aids which now includes screening
for cryptococcal infection and preemptive and preemptive treatment and this and we think that this is very
this is very is very very good so um we jointly with minister of health
through the national aids control program conducted several engagement workshops
with implemented implementing partners um and these are shown in this
in the all in these slides and during this meeting we share the challenges as i said early and mitigations
and then we develop the national training material and the ministry in those uh development
of this training material is a preparation for national scala scale up and the also optimistic infection
national monitoring tool and the under the tool now is including
meningitis working with these partners um announced supporting scale up in
more than 200 facilities countless countrywide in almost
26 regions in the country so the the scale-up is is ongoing um
and we are only providing some technical support to the ministry and the implementing implementing partner
so uh we as i said we are we are scaling up crypto coco crypto cocoa antigen uh
screening and the preemptive uh treatment with fluconazole
as shown in in reps that in the clip but already we have a funded project um
professor tom eluded into this area to evaluate more a more potent regiment
for asymptomatic uh cryptococcal antigen positives individuals has
shown in this in this case there is a need to address the excess mortality that was observed
in both two studies uh the remstart and trip between cryptococo
uh antigen positive and the a and the negative and therefore uh i want to finish up by
saying that um already we are about to start a multi-center trial
is about to start now in tanzania and south africa to evaluate the the preemptive treatment
uh the effect of preemptive treatment with fluconazole and cytosine
so um i would like to finish i would like to stop here because of time and i acknowledge
all people that contributed into these two projects uh and my my
my my partners from uh from uk institution um the implementing partners in tanzania
the ministry of health for really taking this very very positive and we we think that this was a
successful uh intervention implemented thank you very much thank you very much to the panel i think
that was really you know nicely done you know a significant body of work over several years have been
presented um starting from very small scale uh you know um studies to you know quite
robust multi-center multi-country clinical trials and we’ve seen how all of this has fed
into global guidelines and ending up with
you know national guidelines and policies and scale up with a good example from
tanzania we don’t have much time but maybe just two questions that uh you know i’ve
picked up um the first question maybe you can take this and what is the effect of antiretroviral viral
treatment and breaks on the prevalence of cochlear meningitis
well i i i don’t think anybody really knows i i think i i think
that the key is when you stop taking antiretrovirals um the the suppression of the virus
goes away the the cd4 count starts to drop and then you are at risk of developing
cryptococcal meningitis again i think it’s fair to say that there is still a lot of people who are
either starting treatment late or who are fading on treatment and therefore developing cryptococcal
benefits so this problem is going to stay for a long time and as this work shows if you can get them over
the cryptococcal meningitis treat that then you can get them back onto antivirta virals and then to a long survival thank you thank you
for that response um david during your talk you you did mention about um you know an issue of wisdom
intracranial pressure um you know with um patients with cryptococcal meningitis
um within the current treatment and regimen you know how is that managed is there now a standard drug
that so i i think it’s fair to say that this has been for many of us who have worked in this field for some time the most frustrating element of
managing this disease or uh it’s uh there’s no doubt that this is a this is a disease which
the the raised intracranial pressure causes huge distress to patients it’s the only disease i’ve ever seen where patients actually ask you to do
lumbar punctures because that helps reduce the the symptoms and despite a number of of trials of
various agents the only current therapy we have in addition to treating the cryptococcal meningitis
is regular lumbar punctures and that would that does reduce the pressure and it reduces the symptoms and there’s
pretty good evidence that it also improves outcome in the in this disease but it’s a very frustrating
area and and something we need to manage much better okay thank you very much david
uh maybe i’ll just squeeze in one last question um fernanda um so from the experience in
tanzania what is the challenge with you know the drug supply
um either for those asymptomatic and patients who are positive or even
just for treating those who are whom cryptococcus indicted
so sorry
okay i think we’ll get tom to answer it yeah so tom tom can you help with that um
question so you’re asking about drug supply in africa drug supply yes yeah
i mean um you know fluconazole has traditionally been the one drug that has been available but even that wasn’t you
know there was a fisa donation program but even even with that it fell through in many countries and many patients didn’t get
benefit from fluconazole amphotericin b has not been widely available
i mean that certain slightly uh countries with with slightly higher
resources like i mentioned botswana south africa zambia have been using amphotericin b for many years but with this unit aid
program that professing fenango talked to that is now being rolled out in more countries
and lastly the flu cytosine of course it’s been a frustration we all suspected it was an important
drug but now we’ve shown that unequivocally that it’s a vital drug and and unfortunately uh these big
generic companies are making it and it’s it’s still early days but it is available routinely in south africa
and it will it is again part of that unit aids program and i’m i’m an optimist that its
availability will increase across the continent
yes so and we are seeing this improvement through unit 8 chai project
is providing access to uh all these diagnostics and medi medicine and
tanzania is one of the seven countries in africa that is
in this uh aid chai project so through that project we are
we are getting this medication this drugs thank you okay so thank you very much i think this
was some very um uh you know exciting session lots of information shared
um the slides are very useful i’m sure if people want to have them you know they can request lots of links
there to follow and thank you for those responses so i just want to thank the panel um you know i think this
one has been very informative and i’m sure there will be follow-on seminars you know to expand
on uh you know some of the exciting results that were some of them highlighted them today
and this brings us to the end of our seminar today thank you
Research Outputs
Tao Chen, Lawrence Mwenge, Shabir Lakhi, Duncan Chanda, Peter Mwaba, Síle F Molloy, Adrian Gheorghe, Ulla K Griffiths, Robert S Heyderman, Cecilia Kanyama, Charles Kouanfack, Prof Sayoki Mfinanga, Adrienne K Chan, Elvis Temfack, Sokoine Kivuyo, Mina C Hosseinipour, Olivier Lortholary, Angela Loyse, Shabbar Jaffar*, Thomas S Harrison, Louis W Niessen on behalf of the ACTA Trial Team (* corresponding author). Health care costs and life-years gained from treatments within the ACTA trial on CM: a comparison of antifungal induction strategies in sub-Saharan Africa. Clin Infect Dis. 2019;69(4):588–95
S.F. Molloy, C. Kanyama, RS. Heyderman, A. Loyse, C. Kouanfack, D. Chanda, S. Mfinanga, E. Temfack, S. Lakhi, S. Lesikari, A.K Chan, N. Stone, N. Kalata, N. Karunaharan, K. Gaskell, M. Peirse, J. Ellis, C. Chawinga, S. Lontsi, J.-G. Ndong, P. Bright, D. Lupiya, T. Chen, J. Bradley, J. Adams, C. van der Horst, J.J. van Oosterhout, V. Sini, Y.N. Mapoure, P. Mwaba, T. Bicanic, D.G. Lalloo, D. Wang, M. C. Hosseinipour, O. Lortholary, S. Jaffar*, T. Harrison*, for the ACTA Trial Study Team. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa New England Journal of Medicine. N Engl J Med. 2018;378:1004-1017 (* joint senior authors). DOI: 10.1056/NEJMoa1710922
Beardsley J, Wolbers M, Kibengo FM, Ggayi AB, Kamali A, Cuc NT, Binh TQ, Chau NV, Farrar J, Merson L, Phuong L, Thwaites G, Van Kinh N, Thuy PT, Chierakul W, Siriboon S, Thiansukhon E, Onsanit S, Supphamongkholchaikul W, Chan AK, Heyderman R, Mwinjiwa E, van Oosterhout JJ, Imran D, Basri H, Mayxay M, Dance D, Phimmasone P, Rattanavong S, Lalloo DG, Day JN; CryptoDex Investigators. Adjunctive Dexamethasone in HIV-associated CM. N Eng J Med 2016 Feb 11;374(6):542-54. doi: 10.1056/NEJMoa1509024.
Mfinanga S, Chanda D, Kivuyo SL, Guinness L, Bottomley C, Simms V, Chijoka C, Masasi A, Kimaro G, Ngowi B, Kahwa A, Mwaba P, Harrison TS, Egwaga S, Jaffar S; REMSTART trial team. CM screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial. Lancet. 2015; 385: 2173-82. DOI: 10.1016/S0140-6736(15)60164-7
Day JN, Chau TTH, Wolbers M, Mai PP, Dung NT, Mai NH, Phu NH, Nghia HD, Phong ND, Thai CQ, Thai LH, Chuong LV, Sinh DX, Duong VA, Hoang TN, Diep PT, Campbell JI, Sieu TPM, Baker SG, Chau NVV, Hien TT, Lalloo DG*, Farrar JJ*. (* joint senior authors), Combination antifungal therapy for CM. N Eng J Med 2013 Apr 4;368(14):1291-1302. doi: 10.1056/NEJMoa1110404.
Parkes-Ratanshi R, Wakeham K, Levin J, Namusoke D, Whitworth J, Coutinho A, Mugisha NK, Grosskurth H, Kamali A, Lalloo DG; Cryptococcal Trial Team. Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: a double-blind, randomised, placebo-controlled trial. Lancet Infect Dis 2011 Dec;11(12):933-41. doi: 10.1016/S1473-3099(11)70245-6. Epub 2011 Oct 6.
Shiri T, Loyse A, Mwenge L, Chen T1, Lakhi S, Chanda D, Mwaba PMwaba P, Molloy SF, Heyderman R, Kanyama C, Hosseinipour MC, Kouanfack C, Temfack E, Mfinanga S, Kivuyo SKivuyo S, Chan AK, Jarvis JN, Lortholary O, Jaffar S, Niessen LW, Harrison TS. Addition of flucytosine to fluconazole for the treatment of cryptococcal meningitis in Africa: a multi-country cost-effectiveness analysis. Clinical Infectious Diseases, Volume 70, Issue 1, 1 January 2020, Pages 26–29,
Kimaro GD, Guinness L, Shiri T, Kivuyo SKivuyo S, Chanda D, Bottomley CBottomley C, Chen T, Kahwa A, Hawkins N, Mwaba PMwaba P, Mfinanga SG, Harrison TS, Jaffar S, Niessen LW.Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: a cost-effectiveness analysis. Clin Infect Dis. 2019 May 31. pii: ciz453. doi: 10.1093/cid/ciz453.
Global Scale-Up HIV Self Testing: Reaching Vulnerable Populations
Professor Miriam Taegtmeyer and Professor Frances Cowan are key partners in the STAR initiative which aims to stimulate the market for HIV self-test kits through supporting countries in Southern Africa to scale-up self-testing.
LSTM developed and rigorously evaluated innovative test delivery models in Malawi and Zimbabwe that catalysed a supportive regulatory, policy and funding environment both regionally and globally. Seventy seven countries now have HIV self testing policies including 23 in Africa.
Availability of HIV self testing has resulted in rapid scale-up with increased testing coverage particularly among vulnerable, underserved and key populations worldwide. STAR has provided 4,500,000 HIV self-tests across Southern Africa (>2,000,000 for STAR research) and catalysed procurement of another 8,000,000 from major funders. Four manufacturers now have WHO pre-qualified HIV self-test kits available on the world market.
so welcome everybody to the relaunch of the lspn seminar serious series in our temporary
i hope online uh format and so we’ve got today and
we’ve got a number of a series of um speakers based um in here in liverpool and also
in zimbabwe and malawi um and so we will be using the chat um
forum on here on teams for for any questions so please do post questions that come to you as you go and
then i will be reading those out at the end of the seminar so this seminar is one in our sporadic
series of impact seminars that is celebrating the impact of the work um research at lstm
and our and our partners and i think as my role as uh ref coordinator i can
say that the most enjoyable partners have been learning more about the reach and the impact of the work that we have so
behind all their headline grabbing uh grant successes and high profile publications are the really
important stories of exactly how our research is impacting on the communities that we
work closely with and the seminar that we’re going to hear today on the scale-up of hiv
self-testing i think is it’s an excellent example of just um the scale of the reach and the impact
of the work and i think that we don’t really often take enough time to to reflect and
to celebrate these stories so i hope you would um enjoy this seminar i’m really looking
forward to hearing from our um we’re going to be hearing from six different speakers representing the
team working on hiv self-testing across lstm and we’ll be starting with um professor
francis cohen uh for calling in from zimbabwe so welcome francis so
um good day everybody delighted to be here i’m actually in london rather than zimbabwe today but
um i will be back in zimbabwe on friday it gives me huge pleasure to introduce
this impact case study on global self-testing on behalf of the lstm self-testing
group you can see the names of the people who are going to speak listed on this slide but there are others in the
team who will refer to as we go through so i’m sure it’s not new to many of you
here that unaids has set a fast-track target to
end aids by 2030 and to do this we’re going to have to scale up
essential hiv prevention and treatment approaches to allow us to outpace the epidemic
now the entry point to accessing both prevention and treatment is hiv
testing unaids have testing targets and by 2020
the target is that 90 percent of people with hiv will be aware of their status
referred to as the first 90 and then that 90 of those are on treatment and 90
percent of those on treatment are virally suppressed in zimbabwe and
malawi which we’re going to talk about a lot today in 2019 it’s estimated we did
achieve the first 90 for the first time since the start of the aids epidemic so
that’s fantastic news but what these broad brush targets hide
is the huge disparities in access and uptake of testing that exist and that hide
real inequities in coverage as we move forward trying to attain
the goal of reaching 95 percent of people who know their status
with testing to ensure that 95 of people who are hiv positive know
their status it’s going to get harder to reach those people who have not previously tested and we’re
going to need increasingly acceptable innovative and
easy to access approaches and this is where hiv self-testing comes in
so what is hiv self-testing it’s where an individual performs their own test and interprets
the results and because you can do a self-test pretty much anywhere
it allows for innovative delivery strategies we believe and i think the research that
we’re going to present will show that you can use self-testing both to reduce the testing gap
and to reduce inequities in coverage so um lstm has been part of a
global body of work which has started with formative work moved on to
exploring issues related to early scale up and most recently doing really
broad and extensive implementation research to optimize the delivery of self-testing
at scale and we’re going to present examples of all of those to you today
um i’m going to hand over to peter macpherson to tell you about some of the scene setting
work that was conducted in malawi um in the in around the time of the
previous ref actually so thank you very much francis
and good afternoon everybody my name is peter mcpherson i’m a public health physician and i’m
based in malawi and blanta at the malawi liverpool welcome clinical research program where i head
the public health research group and and i want to take you back to 2010
and where we were only just beginning to start thinking about self-testing for hiv and around about 2010
he’s having treatment had been available for a few years in africa people getting onto treatment
lives were being saved but still very few people probably less than half of people
were aware of their hiv status and were able to access the benefits in terms of life-saving treatment and preventive
strategies if you wanted to get an hiv test the usual way that you received one
was either attending a health system a health center even if you were sick or or to request a
test or perhaps within your community there was something called voluntary counseling and testing um
mobile or fixed services where you could go and request um heavy testing but what we and many
others found was that people you know if you wait for people to come to health facilities until they’re sick
that’s very often too late transmission has already occurred and they they often have substantial morbidity
and a high risk of mortality or or alternatively if you ask people to motivate themselves to attend
dct services very often they are not accessible or acceptable to to quite a lot of
population groups who are not otherwise all served next slide please
so a number of groups around the world including ours and blanthar have started exploring hiv
self testing so there have been some studies from francis and zimbabwe looking at early approaches
to hiv self-testing looking at feasibility in emergency departments in the usa and
interestingly who had been a multi-country survey amongst health workers showing
that health workers were frequently testing themselves um you know in between seeing patients
in clinics so there was a clear momentum towards uh you know an approach to history testing
that put people in power and in charge of the loom testing schedule and what really catalyzed action was the
development of the earthquake and test quake this is the the the the kit that is shown
um in the image here and can be used on oral fluids by people themselves or all with platforms so the image in
the middle here the map so it’s part of lantar where i work this is actually within indorandi very densely populated neighborhoods
where one in five adults are hiv positive and way back in 2010
myself aubrey chocolate corbett and others i set out to explore whether heavy self-testing could be used
whether it’s feasible uh to implement that scale within these sort of densely populated urban
areas we identified health surveillance assistant areas so these are geographically
defined areas within um within the city where health workers have responsibility for the population
and we identified neighborhood champions essentially um who got training in delivering
self-test kits distributing them from their home and receiving test results as well
and so the very first formative study after our initial assessments uh was one as part of a cluster
randomized trial with a total of 16 660 people and i did this trial with
those as part of my phd back in 2010 was welcome and so we
throughout 14 different clusters or neighborhoods in the city we we trained and identified these
neighborhood distributors for self-test kits and we invited people living within their neighborhoods to come to the
neighborhood councillors place of predators collect textbooks and introduce them and tell us the results
next slide and these data show the results of the
first year of implementation of hiv self-testing in blancar which was around 2012 broken down by age
group and sex and these results are were very exciting to us although children published them across medicine back in
2015 and what we were extremely excited about was an uptake of hiv self-testing was
extremely high particularly amongst young men and women who we’ve found previously
were a very difficult group to reach with heavy testing uh so you see for example in the 16 to
19 year old woman essentially by one year every young woman in these neighborhoods had tested for
hiv next slide please overall over the first 12 months of the
self-testing intervention 76 of the entire adult population self-tested for hiv
and 35 of those people were first-time professors and we repeated this in a second year
and found very similar rates of coverage with about 75 percent of the population
testing in a second during the second year but a much lower number of people testing for the first
time to get considerable
and we also asked people about their preferences next slide and what we found very clearly that was
that people were very keen to self-test in the future if they had already self-tested so people didn’t want the inconvenience
of going to health centers or to hospitals or they didn’t want the lack of privacy that came with people
coming door-to-door they wanted to receive self-testing from the counselor or to do it in private
themselves next slide and so finally just to complete that
that kind of cycle of implementation we were also very much aware that very few people who tested
hiv-positive were linking onto effective treatment so at the time only one in five adults who tested hiv
positive and blantar successfully linked to antiretroviral therapy without an interruption within
the first six months so we randomized seven of those fourteen neighborhood clusters
that had got access to safety salting self testing to additionally receive
the option of starting treatment for hiv at home after the self-testing positive and in the control controllable patients
have the option of going to the facility to start treatment as they usually did and what we saw was that three times as
many people in the population started art when treatment was away was made available at home after self-testing
so taking together these five these findings that we published in gamma in 2014 were very powerful suggesting
that you could achieve very high coverage of hiv self-testing in busy urban populations that are otherwise
hard to reach and you could get people on to treatment rapidly as well um and so i just want to thank stop my
portion of the talk by thanking the large number of the team particularly liz and all of you and who contributed to this huge body of
research and i’m going to hand over to the next presenter now
so peter has um explained the wonderful work that they
did in malawi but at the time that work was finishing still the picture on the global stage
was not great so fewer than half of people living with hiv knew their status
there was relatively limited evidence for self-testing other than the work that had been done
in malawi kenya by miriam and a few other settings only three countries in the
world have policies in place and only two are high income countries were actually implementing self-testing
and it’s worth mentioning that in several countries around the world hiv testing was expressly prohibited by
law there was no normative guidance in place no quality assured hiv self-test
products for low and middle income countries and very limited policy and regulation
we’ve already discussed the testing gap and disparities in testing access
and the lack of testing delivery options it’s worth also saying that the worst
huge concern over so the potential for social harms um and something that was often raised
when you brought up self-testing was that people the fear that people might test themselves get a positive result
and go off and kill themselves so this was a real deterrent to making
hiv self-testing available so peter’s already described some of the
really important work that lstm led that was influencing
the start of the discussion around self-testing another piece of uh the puzzle critical
really to um scaling up was a meeting convened by lstm by miriam tegmeyer
and who and unaids and that was the first international
symposium on self-testing which resulted in an aids and behavior
supplement and really set out the research agenda
for um self-testing to try and change the try and change
the environment the global environment so that self-testing could be scaled up
so as they say the rest is history shortly after that meeting unitade
launched a call for funding to which a team of us applied
the team was led by population services international and then there was a
research consortium led by liz corwer to tell shtm with myself and miriam as deputy
research directors um initially based in malawi zambia and zimbabwe but subsequently expanding
to the eastward ii and south africa we work closely with ministries of
health and a really important partner was the who hiv
department we put in of course a stellar proposal and
that resulted in funding of something called the star initiative star stands for self-testing
africa here are the members of the lstm
star team on this slide many of whom you’re going to hear from today
so in 2014 i’ve already indicated there was work to be done
formative early scale up and optimization this had it had to happen both in terms
of informing the policy needs and also the
market needs and in fact the title of the star grant was a grant to shape and
stimulate the market for hiv self-testing globally so
formative work was planned and undertaken by target group to
understand how to generate demands the accuracy safety and acceptability of
self-testing and how to encourage linkage to either prevention and care
as well as studies on basic costing early advocacy and legal policy and regulatory review
and then these themes got developed further but as we proceeded to the early scale
up research and implementation research to optimize models
importantly we were responding directly to the demands of who
and ministry of health and our findings of our research fed directly into
technical updates country level and who level normative guidance
so i’m going to move on to russell daycamp who’s going to take us through the legal policy and regulatory
revision thanks very much uh francis and i just want to acknowledge my other team members vicky watson from
lstm and eliot cowan who used to work with the fda who both assisted with the work i’m
about to present on next slide please so um so we would task it looking at the
regulatory uh and to a certain degree the the policy side of hiv self-testing so why we looked
at uh regulation is essentially it’s the law so people have have to do
it uh so with um hiv self-testing it obviously both encompasses both the public sector and
the private sector so uh policy alone would only really uh cover the
the public sector so um with uh regulation of uh hiv self-testing we
already had to look at the regulation of in vitro diagnostics in general so to include all diagnostic tests and what
we had to look at but with a specific focus on the challenges around hiv self-testing so with regulation you have to balance
the quality of the product uh with actually getting a product on the market so the needs of
the public with the needs of the manufacturer so uh first of all we did some formative work
back in the start of star in 2015 where we looked at uh key stakeholders
we’d identified in this sector so this was mainly people within policy mainly people within the regulatory bodies
and people within the national reference labs with expertise in hiv and self-testing
uh and doing this through uh qualitative methodologies in-depth interviews uh we
found that there was really a lack of understanding of what regulation actually was amongst
those who weren’t in the regulatory uh bodies uh and we also found in apart from one
country there wasn’t really a focus on in vitro diagnostics for regulation um much of the efforts was put into into
pharmaceuticals which uh was a trend globally um because of this lack of understanding
there was also a lack of collaboration uh between uh those with the technical
expertise uh those in policy and those involved in regulation so much that uh
in some countries regulators were not talking to these uh these experts at all people in policy and were forging out a
completely different path uh when developing their regulations um there was also
uh concerns that francis mentioned earlier around social harms to do with hiv self-testing
across all the groups broadly there was also a con concerns around the performance of hiv
cell tests in the uh in the hands of intended users would they do them accurately uh and uh there was an emphasis really
on the on the quality side rather than the market access side so um next slide please
um so taking this uh these uh results from the formative work um
we propose an intervention to uh strengthen uh collaboration both within
countries between uh policy uh diagnostic and regulatory bodies
uh and between countries uh in the star consortium that were
to bring forward regulation um so we started these in in 2016 through 2019 uh
with all the countries uh joining in a stepwise process because they joined star in a stepwise process
um and as we’ve said with ministries of health and national regulatory authorities in the reference labs
uh with the idea of of putting together joint plans to develop ivd regulations
and for countries to solve common uh problems that they had and also to promote the concept of
convergence to simplify market entry
into these countries so convergence essentially is making sure that your regulations are as
similar as possible between countries and there’s various ways which you can do this
which i don’t have time to speak about in depth today um so i will move on to the next slide to
show the progress that we made um so this is is the steps that we went through with the countries
uh to develop in vitro diagnostic regulations um which would include hiv self-tests
so the first element was a clear legal mandate so in in one country there there was no uh
legal instrument which the regulator could use for diagnostics i.e they didn’t have the legal mandate to do it so that had
to be put into place and the idea was then next to prioritize ivd regulation among stakeholders so
this is very much around bringing those groups together then to develop convergent regulations
and then finalize them and you can see over the period of star um the three initial countries malawi
zambia and zimbabwe moved uh from uh these prioritization
actually up to finalizing uh regulations south africa was brought on it was already more developed but this allowed
them to share their expertise with the countries that were uh at an earlier stage
and lesotho and suartini joined late but they would be able to at least bring over deregulation
onto the agenda next slide please next slide please thank you very much
okay so uh just to uh kind of demonstrate in in regulatory terms how
uh the star project addressed some of the issues with um regulation
of hiv self-test devices so this slide shows the process of a
of a hiv self-test from the factory on the left through to the
individual on the right and there’s a number of different processes that has to go through to get to that individual so on the left
hand side um we um interacted with wh o p
q and this is a body in who who standardized the quality assessment
process of certain ibds to help them get onto the market and so we work with them to develop a
technical specification series for hiv self-tests we also did various
bits and pieces um in terms of uh improving the way that kits were quality tested on
their way to the individual user and we also identified um potential ways
that the quality of the testing in the hands of individual users which was raised as a concern by
stakeholders uh could be dealt with so this is really around re-reading of tests observation
of people doing it dry blood specimens and also potentially
video support um so next slide please so thank you very much so
uh i’ve already talked about this so this is how we mitigated some of those risks on the last slide um so i’ve
talked about the tss uh i’ve talked about convergence uh so
with lot verification testing um we helped countries introduce testing
that was suitable for hiv self-testing and for the end user performance which is the most risky element of hiv
self-testing there was work on adaptation of ifus which i’ll talk about um the re-reading of test stability so
this was initially seen as a way to um check the quality of people’s
interpretation but we did some experiments around the stability of these tests and found that
in some cases you could use certain tests uh for checking people’s interpretation but
some would uh give false positive results over a short period of time so re-reading was not the panacea that
we were hoping it was and there were also some community preference studies to see which models
communities would prefer and they generally preferred re-reading um so next slide please and i’ll try and
be quick through this because i’m probably over time so we also looked at the group as our whole and this is
many others and the consortium used that usability so this is how people used uh the self-tests um
so this was mainly uh focused around the instructions for use the material that is in the test that tells people how to
do it uh and in short there were differences between rural and urban populations with
rural populations uh performing the test less well with just ifus and this also may have been
related to literacy so there were iterative modicate modifications the ifu’s to make them
um more understandable to those groups and we also found that accuracies
improved when a demonstration video was also um included uh
in uh supporting these these groups uh and then there was adequate accuracy
with those groups so um with all that in mind i’m now gonna hand over
um to the next speaker um who yeah so i’m going to hand over the next speaker
hello thanks russ um so my name is nichola desmond and i’ve been based for many years at
mlw along with peter but recently i’ve just moved back to liverpool school and um so i was involved from the very
beginning of hiv self-testing working alongside liz peter orgu and others and when we conducted
the original pilot test and at that time um we understood that the the biggest policy concern as
francis has mentioned and russ has mentioned was around social harms and this idea that
um self-testing at home may kind of um increase potential for suicide and post
post-result so i thought i got a welcome trust fellowship to explore social harms
and the social consequences of introducing hiv self-testing amongst general populations
from 2012 to 15 um but then within the star consortium we
realized that these these concerns were translating more to you know particularly vulnerable
populations so the work kind of then translated into trying to understand social harms amongst particular
populations that were um considered more vulnerable by policy makers and that
includes sex workers and that’s going to be the focus of the next um the next couple of slides next slide
please so our approach with high risk populations and sex workers in
ins specifically was to explore in-depth the inclusion of hiv self-testing within
other established sexual health programs in malawi um so hiv and sex workers is generally
high in the malawi setting as elsewhere at around 63 prevalence and there are higher rates of
hiv in the underlying community population in the southern part of malawi so this
became our focus um where we worked alongside one ngo that was responsible for
um sexual health services um within the southern malawi setting in malawi um and this was this was
pakishari so pakicherry works across both urban in blantire
and semi urban and rural locations where sex worker populations are encouraged
by sugar plantations such as in chikwawa district or tea plantations such as malangi
district in reality sex workers are highly mobile moving between locations
and from being largely venue based to potentially street or home based depending on their location and they may
move from one type of sex work to another as they move location so pakicherry expected to provide 10 000
kits overall um during the start our star and work with them
but only managed distribution of 5281 through 51 peer educators who are
engaged already within the sexual health programs um we targeted so 57
of those targeted were sex workers aged between 15 to 24 so younger age groups
and of these 4 096 kits were returned and of those around 33 were positive
but only 61 of those linked to care for the first time and we don’t actually know how many
overall were first time versus repeat testers for this cohort however what we do know is that there
were high rates of retesting amongst those with prior knowledge of their positive status and already on art
and it’s likely that many already known positive cases were re-testing to confirm their current
status so linkage is also likely to have been under-reported in this particular
population as sex workers often use aliases when they’re attending irt services
or they may attend services outside of their local vicinity because of issues around stigma so we
conducted a nested mixed methods study um within the package area distribution in order to
monitor social harms as a result of hiv self-testing now this followed a formative stage
where we conducted a rapid ethnographic assessment along with key in um key informant interviews
so we recruited over all 265 parties participants out of a total of 300 that
we planned to to recruit um across both street and venue-based sex workers and this was
across the three sites blantar chicago and melangjo so a baseline and immediately which was
immediately following hiv self-testing and then again at three months post um post hiv self-testing we used audio
computer self interviews to explore sociodemographic sexual behavior testing
history and the focus here on social and social harms we conducted also alongside the akasi
a pictorial longitudinal diary study for all sex workers enrolled
at baseline um in order to understand through that daily sexual behavior
reporting on a daily basis and social harms as experienced on a daily basis alongside weekly reporting of hiv
testing behavior so 40 of the women within the 265 were also recruited to
a qualitative serial biographical interview study and they were interviewed at baseline
and again at three months next slide please
so most women within the cohort i’m just gonna report on a few of the key findings from this study
so most women have received only primary or lower than primary completed primary education and
the majority had also previously tested around 87 percent had already had um
had experience hiv testos testing there were high rates of intimate
partner violence reported at enrollment around 48 and this reflects um general population
reports of into intimate partner violence in these types of settings um so we only have data complete for 130
of the akasi and diary um so that the the results that i’m reporting on here the numbers i’m
reporting are based on that 130 population so key to um understanding hiv
self-testing decision-making processes were the power relations that pre-existed and
then were reinforced between the sex workers themselves and the peer educators and venue owners
so peer educators educators in this delivery setting were seen both as supportive but also
as exerting some pressure on on the sex workers um overall 29 over 130
um events um there were there were 29 events of coercive testing reported out
of 130 participants and 28 forced disclosures between
sex workers um but um sorry forced disclosures
um of sex workers um which um related to um disclosures that
have been forced by intimate partners family members peers but particularly again the peer
educators the peer distributors also relationship problems were more
likely to have been reported if hiv self-testing was initiated by someone else
now this was obviously slightly concerning so we explored this this further but we found that there was
some evidence for an increase in verbal abuse immediately after testing
but no evidence that this was different for self-testing than for standard testing and we also found that whilst regret
at having itself tested was reported often in in younger sex workers this regret
reduced over time so we’re still conducting more analysis on social harms and
that data will be out soon next slide please
so this work um has contributed um both the both the work that i’ve just
um um [Music] presented here and the work amongst general population has contributed to
both national and international policy decisions as francis has already highlighted and we’ve been involved as a star
consortium in the who steering advisory groups and guidelines development groups as
well as contributing to key key population policy developments and sitting on for example the malawi
hiv self-testing task force so the who um recommended
as we’ve also been sick we’ve also um played a key role in developing the
guidelines the who recommendations for hiv self-testing and assisted partner notification in
2016 as well as the market-driven response that has progressed from there
for example with the who um pq guidance and the erpd through the global funds that russ
has already talked about um the star consortium work i think has contributed very much to moving forward
the debate and um highlighting the fact that social harms are
are less of a concern are much lower than expected when um when discussions around
self-testing first came about in around 2012. um i think i’ll end there and pass over
to euphemia who’s talking about community-based self-testing
thank you very much nick hello everyone so i’m going to talk about um or before
i do that i’m ephemia swandan i am based in zimbabwe where i’ve been leading the implementation
of the various research that has been conducted on star at the zimbabwe site
so i’ll talk about the community-based hiv self-testing which is a model that we implemented and
evaluated a lot when we were bringing self-test kids to the people
next slides please so we started this model of community
based distribution by a pilot that we conducted in zimbabwe where we distributed kids door-to-door
and we managed to distribute over 8 000 kids within a short within a short period of time within
three months and this work was important in informing how we scaled up hiv self-testing
at community level within the phase one of star as you will see on the figure on the
right within phase one of star we distributed over 6 000 kids sorry over 600 000 kids
with the majority of the kids having been distributed using the community-based distribution model and
as nick has mentioned this work was also important in informing the wh or guidelines that were
released later in 2016 next slide please
so as we developed the models for actually all the models that we
implemented on staff one of the key research points that we
did was to conduct research on people’s preferences for how hiv self-test kids could be
developed and as we developed the community-based distribution model we
conducted district discrete choice experiments in order to find out how best people would
prefer to access these hiv self-test kits so just to start by defining the discrete
choice experiments there are experiments where an individual is given a set
of alternative programs as shown on the picture on the right and the characteristics of the programs
are given in this case for example you can see the person is told the alternative one is
the characteristics of alternative one are given um and the characteristics of alternative
two are also given and the person is asked to make a choice between those programs
based on the individual characteristics and this is important in that it shows us what peop what
preferences people have for programs and it also allows us to see the trade-offs that people are making as
they are making those choices and this is important information that programs
need as they make decisions on what to on how to format the programs that
distribute the hiv test kids so uh across all the countries that did
the discrete choice experiments we got consistent findings where it was clear that people favored
the distribution to be done by lay counsellors rather than community of rather than health workers
there was trust of people who lived within the same communities to be the ones who were
distributing the hiv self-test kids and people did not want to have to collect the test kits from mobile
clinics or and also they wanted the kids to be distributed directly to them
without having their sexual partners being the ones who are given to distribute that is they were not in
favor of secondary distribution being carried out by their partners and in terms of linkage to hiv care
people were favoring that after they had self-tested they should be able to
get linkage to for example confirmatory testing hiv care services
to be done in their homes or at the councillor’s homes and across all studies it was also clear
that people are really against having to pay for services and this is something that was consistent
even with our other work another pricing experiment that we conducted in zimbabwe it was clear that people would not want
to pay for hiv testing so that’s something that programs would need to be aware of as they bring the test kits or even as
they look at what the pricing options are next slide please
so here i am we are showing the results of a community-based
distribution study a trial that we conducted in zimbabwe in 38
clusters this com in this uh study particip
we conducted door-to-door distribution of hiv self-test kids across all communities so they were they
weren’t any communities that did not have hiv self-test kids the only difference was whether
the distributor’s weight was the way in which we distributed the sorry was the way in which the
distributors were paid for for the work that they had done and what we see from this door-to-door
distribution strategy where we distributed over 80 000 self-test kits was that we were able to achieve a very
high uh uptake of hiv testing with um 88 percent of people reporting that
they’d ever tested for hiv and this was very high significantly
higher than a 75 percent um coverage that he had recently been
um it’s a 75 percent uptake of ever having tested for hiv which has been
recently reported in another population-based study that had just completed
when we started this work of importance in terms of overall
coverage of self-testing in the community we found that community-based distribution was
associated with a 50 coverage and we were very happy to see that it reduced inequality because men
and young people who are typically groups that have a lower uptake of hiv testing
also showed coverage that was similar to what was seen for the general population
where we had 46 percent coverage for men and a similar number for young people less than 25 years
next slide please so this is now showing the impact of
community-based testing across the initial star countries and what you can see for both zimbabwe and
malawi we show high coverage of 50 and 42
in zambia the coverage was slightly lower it was lower
significantly because they had a different model of our community-based distribution which was different from the
distribution that we employed in both zambia and malawi and what you can see as shown on the
figure to the right is that the model is very good in reaching the key people that have
traditionally been left behind in terms of testing so the young people and the males were equally covered
by hiv self-testing and another model that we have employed is community-led self-testing where we
have engaged communities to take a lead in distributing hiv self-test kids in their community
and we found that this has been a very well accepted and well received intervention with
malawi reporting a very high coverage of 74 percent after
community-led distribution of hiv self-test skills was done we’ve also conducted a study in zimbabwe
where we implemented community-led hiv self-testing but the results haven’t been presented
yet because they are still under imbaku next slide please
so we haven’t seen the effect of community-led distribution on uptech
it was also interesting for us to be able to see whether this translated to linkage to poster services yes this
is really important our self-testing alone will not give us the public health impact that we want if
people do not link to poster services and so we conducted a difference in
different analysis where we went to the health facilities that were catchment areas of the
communities in which we were conducting the hiv self-testing research and we collected monthly number of art
initiations in those communities where in those facilities that were catchments of the self-testing
communities and in those facilities that were not catchments of
hiv self-just kids and we were able to see that in facilities when
self-test kits had been distributed there was a significant increase in the number of art
initiations during the period of hiv self-test kids and what was interesting was to see that
before self-test kids was introduced as shown on the figure on the right the rate of initiation was the same but
there was a clear difference during self-test distribution and this difference
disappeared after the campaign style of self-test distribution had been
completed and we can see from the numbers there that this increase
in initiation was was significant it was a 27 increase
that we were very pleased about next slide please
so what about the cost effectiveness um this is uh was an important question for us in
terms of how how cost effective is community distribution
but what we are more interested in what’s more critical is the cost uh per person uh
hiv-positive person identified and what we’ve seen from the research that we’ve done and
the research that we did uh prior to start is the fact that community-based distribution is really expensive
whether it’s hiv self-testing or the provider-delivered testing and
as shown on the figure to the right we saw very high unit costs and so
it might be important to see how we can target hiv self testing kids at a community level bearing these
costs in mind and it’s likely that as we do a broader community level distribution we might be
able to benefit from economies of scope as we go forward next slide
please so in summary just summarizing the
impact of community-based distribution we see that it’s a very
important model the image on the right is showing the importance of community-led distribution
in the modeling study that we did showing that for some key groups it would be
difficult to reach the first 90 without hiv self just testing i have already
discussed that it was able to increase coverage particularly among men and young people
and we have seen the potential value of community led testing and as we go forward it
might be important to think about how community-based testing continues
policymakers might think about maybe conducting periodic campaigns so that there is
potential to reach even those people in a campaign style and be able to meet
the pent-up demand and not do it on an ongoing basis based on the cost
thank you i’ll hand over to miriam thank you euphemia my name’s mike
and i had the community health systems group here at lstm on star i’ve been the deputy research
director with francis and i’ve led the qualitative research network
what has been so brilliant about star is the scale of the impact that star has
achieved it really has changed the global debate around hiv self-testing and for me
as a community health systems person i’m really excited about the way it’s
changed the debate about self-care not just for hiv testing
but for putting people and communities at the center of universal health
coverage and we targeted next slide please francis we targeted sort of three main areas for
demonstrable impact increased access to the kits in these in low and middle-income countries
reaching large number of people previously untested and shifting policy and practice and
i think we’ve now showed you some of the underpinning research that we targeted at these three areas
but really what brought this together was the leadership the vision and the collaboration the way we brought
people on and so this was a group effort it was ministry of health it was russ
has told you about manufacturers regulators reference labs communities themselves
um comms people ngos civil society it was having those conversations and
working in a coordinated way to ensure that our research was meeting their needs
next slide and so some evidence of the impacts firstly on products
staff through its sheer size and ambition was able to drive down the price of test
kits and reducing barriers to market entry for manufacturers
so a market landscaping done by psi the regulatory work we’ve talked about
the wh show involvement the accuracy work they um caused the bill and linda gates
foundation and sift to do a buy down of price of in june 2017
so prices went right down and that enabled ministries to step in
and say right scale up and as we speak now there are four tests that the who
has pre-qualified um above and beyond this um
the erpd process next slide um the direct impact on testing is now
huge four and a half million tests have been distributed through style another eight million have been um
purchased by others like global fund by pepfar and so the direct impact uh is huge and
we’ve seen very limited evidence of harm but created mechanisms
alongside this distribution to to monitor that and for the next
slide please and it’s influenced policy globally so
right now 77 um countries have hiv self-testing policies in place and more
are coming on board and we’re seeing our work uh both as lstm and a star referenced in those policies
across the world not just in sub-saharan africa next slide
i’ve been quite involved in the coveted response here in liverpool and it’s made me reflect a lot on
self-testing um in general and what lessons we’ve learned and what platform style has
created for covid in in low and middle income settings
where the same in vitro diagnostic regulatory frameworks will also be applied
to covered point of care diagnostics and covered self-tests and and the same need to bring people
together across disciplines the same need to communicate and work with our community
and have person-centered approaches to scale up um are going are going to play out
for example the instructions for use for doing your own sars cov2 self-test which is a little
more uncomfortable than an hiv self-test i have to say will need to
be optimized for communities to use them but without self-testing true decentralization
and proper track and trace systems won’t be in place so i’m going to end there and
hand back to hillary um and thank you all very much for listening
to to this seminar so thank you to all our speakers for a
real fascinating tour through um all the different steps that need to be
put in place to really have this impact we are nearly out of time but i am going to try and take
one or two questions and if we can and i’m going to see if i can see um
well i’ve got a question actually yet about um sustainability of the
testing model and that was something also that i wanted to pick up on um about the
i think you mentioned that they were i think both russ and miriam mentioned about the role of um the
private sector and the subsidies um i think from gates foundation to make them accessible
what’s the future for that and what’s the have the cost of production of these
kits come down to a level in which the subsidies will not be needed or or how do you see the future if donors
withdraw from this yeah i mean i think the the global debate has shifted so much that the combination
of price reductions and prioritization in ministry of health
um has has made that sustainable what we’ve got to be careful with here
is replacing something that already worked that was maybe cheaper
with something that’s more convenient and maybe a bit trendy and that’s part of what we’re trying to
unpick with the data uh francis or euphemia might want to add
on sustainability in zimbabwe
[Music]
yes um i can add in terms of sustainability it’s been good that as we were
implementing self-testing we’ve been working closely with ministries of health and other key players in the hiv
testing services department and so this is something this is a model that has been adopted
by all the players and funding has been mobilized for hiv self-testing
funders so it’s something that is being continued because it has been adopted at
country level and perhaps just to add briefly one of
the issues at the start was that because the policy
environment was not friendly it wasn’t worth manufacturers trying to develop a kit but we’ve gone
from a situation where there was one kit available at a high price in a couple of high income countries to
where there are four kits competing um for the market share and that
has a way of driving down the price of kids in the longer term yeah i’m going to just take one last
question because i realize that we’re on two o’clock there’s a question from helen and uh asking about the acts um
what what thing happened had on enabling children to access hiv testing
and leakage to care you feel me again i think yes um so
in in the research that we have done we have followed ministry of health guidelines on the
edge of consent for hiv testing where the minimum age is 16 years old
so we were not as part of our research and implementation offering hiv self-test
kids to younger people but to people younger than 16 but in the younger people
the adolescents we’ve already said that there was a very it’s presented a very huge increase in
the uptick of testing there has been research that has been
conducted among young people um where their caregivers have been
consenting for hiv self-test kids but i haven’t seen these results as yet i’m not sure if
francis has seen them
i have seen them they’ve been actually published i think in lansing global
health looking a study done by rashida ferand and colleagues in zimbabwe
and looking at the effectiveness and cost effectiveness of testing for children by their
caregivers and that actually did make a difference to
the uptake of testing in children of people who were reluctant to bring them
to facilities to test
okay thank you i think we we are out of time now so i’m going to forward on any remaining questions to the
um our speakers today and they can pick up on those but thank you again to all our presenters
and thanks to everyone for attending this session thank you
thanks for joining us thank you
The ACTA Trial
Advancing Cryptococcal Meningitis Treatment for Africa. The Acta trial aims to significantly reduce the mortality rate from HIV-related cryptococcal meningitis in Africa by developing novel treatments which can be implemented in resource-limited settings.
Global Health Research Group on Prevention & Management of Non-Communicable Diseases and HIV infection in Africa
HIV, diabetes, and hypertension are major determinants of the massive disease burden in Africa and the provision of accessible effective care for these conditions is probably Africa’s biggest health challenge. The aim of the group is to build a programme of research to inform integrated approaches for the prevention and management of HIV, diabetes, and hypertension.
HIV Research at LSTM
LSTM has seen a major expansion in HIV-related research. Following on from the appointment of Shabbar Jaffar in mid-2015 as Professor of Epidemiology and Global Health, in August 2016, we recruited Frances Cowan, as a Professor of Global Health. Both focus on HIV-infection. The HIV research portfolio now spans studies on HIV-prevention to research on the management of late-stage HIV-infection.