AIDS 2016 special
The 21st International AIDS Conference (AIDS 2016) was held in Durban, South Africa in July. This year there was a special emphasis on using testing, treatment and prevention methods to bring about an end to the HIV epidemic by 2030. For all of aidsmap.com’s news from AIDS 2016, see www.aidsmap.com/aids2016.
Still no transmissions seen from people with an undetectable viral load in PARTNER study
The PARTNER study, which two years ago created headlines by proving that the chance of an HIV-positive person with an undetectable viral load transmitting their virus was low to zero, released new data at AIDS 2016 that further refined this estimate. The latest estimate involves 888 couples, 38% of them gay male couples, and encompassed 58,213 condomless sex acts. In 2014, the highest-likely estimate for the chance of between-couple transmission via any condomless sex was 0.5%. The new data narrows this ‘upper confidence interval bound’ to 0.3%. The upper limit for the likelihood of transmission during the riskiest sex act – condomless anal sex where the receptive partner is the HIV-negative one and there is ejaculation – is 2.7% in gay men, down from 4% in 2014.
Fifty-five (6.2%) of the HIV-positive partners reported a detectable viral load at some point in the study. But, though there were eleven new HIV infections in the HIV-negative partners during the study, ten in gay men and one in heterosexuals, genetic sequencing showed that in every case, the virus acquired by the HIV-negative partner was quite different from their partner’s virus.
Comment: PARTNER illustrates the difficulty of proving a negative. Zero transmissions implies zero risk. But PARTNER can only establish this as a probability, not an absolute fact. What the larger number of sex acts in the 2016 data mean is that the highest-likely risk of transmission has fallen – it becomes less probable that we have ‘missed’ a transmission. So, the 2.7% receptive anal sex figure does not mean this kind of sex is, if the HIV-positive partner is undetectable, actually riskier than other kinds of sex: the most likely transmission probability remains zero. Final data in 2018 will further narrow the window of probability.
Vaccine comfortably out-performs previous effective candidate
A new efficacy trial for an HIV vaccine will start this November – only the seventh ever conducted. The HVTN 702 study will enrol 5400 men and women in southern Africa, and is planned to last for four years. It was actually announced on 18 May this year because a pilot study, HVTN 100, had met the criteria for the vaccine being taken forward, but Durban heard how well it had met those criteria.
In 2009, the RV144 vaccine was the first to show signs of efficacy: the vaccine’s effect was real, however, it was weak and tailed off rapidly; a stronger one was needed. Investigations showed that this was due to an unpredicted kind of immune response. The one which will now be used in the big study is like RV144 but is adapted to the subtype of HIV most common in southern Africa.
HVTN 702 will go forward because HVTN 100 fulfilled the potency criteria set. These were that the vaccine should stimulate an antibody response to HIV in 75% of subjects (in fact all subjects responded); that the response should be at least 50% stronger than in RV144 (in fact, it was 3.6 to 8.8 times stronger); that it should stimulate an immune response to HIV in the CD4 cells of at least 36% of people’s CD4 cells (58% of CD4 cells responded); and that 63% of people should show the kind of antibody response that correlated with efficacy in RV144 (over 80% of people showed this response).
Comment: This could be the most exciting scientific result announced at Durban. The HVTN 100 vaccine comfortably out-performed RV144 in terms of creating immune responses that are regarded as indicators of efficacy. However, there is no substitute in vaccine trials for actually giving it to large numbers of at-risk people and measuring how many infections it stops.
Mixed results for treatment-as-prevention trials
Results from several large studies of enhanced HIV testing and treatment were presented at Durban, with differing results. Three of these studies have already been described by aidsmap.com and preliminary results from SEARCH and ANRS 12249 have been published. Durban heard much fuller results.
SEARCH is an innovative trial that offers HIV testing and treatment as part of a larger package that also includes testing for non-communicable diseases such as diabetes and hypertension. The trial randomises 320,000 people in 32 communities to receive the intervention or standard-of-care for HIV. By the end of year two, 97% of people with HIV had been diagnosed, 94% diagnosed had received antiretroviral therapy (ART) and 90% of them were virally suppressed – a remarkable 82% of all the people with HIV in the area.
In contrast the ANRS 12249 study already announced results in 2014 indicating that although it achieved high rates of testing and diagnosis, people seemed reluctant to get themselves to the clinics once diagnosed. The full results confirm this. By the end of the study 92% of people with HIV knew their status and 93% of those on treatment had an undetectable viral load. But only 49% of those diagnosed started treatment, so only 42% of all people with HIV in the area had an undetectable viral load – no better than before. Further analyses are underway to find out why so many people did not start ART.
In Swaziland, the Link4Health or MaxART trial, which offered an enhanced care package at half of the study’s HIV clinics found better rates of linkage to and retention in care in people taking its enhanced package. Sixty-five per cent of people in its enhanced care arm started ART compared with 58% who were offered the national standard of care.
SAPPHIRE differs from the other studies in that it offers pre-exposure prophylaxis (PrEP) as well as ART and was directed at a specific population – female sex workers. The primary endpoint of the study was a reduction in the proportion of a mobile population of female sex workers in Zimbabwe that had viral loads over 1000 copies/ml: it did not test viral suppression in individuals but a population – 60% of whom had HIV already. The intervention group also attended specialist sex worker clinics rather than government clinics, and were offered PrEP if they were HIV negative. By the end of the study 80% of HIV-positive women had been diagnosed, 83% diagnosed were on treatment and 88% on treatment were virally undetectable – 58% of all women with HIV. However, the enhanced provision that included PrEP in the intervention arm made little difference and only a few hundred women started PrEP.
Comment: UNAIDS has calculated that increasing the proportion of people living with HIV who are virally undetectable to over 73% worldwide, i.e. its 90-90-90 target, will bring about 60% of the reduction in HIV necessary to end the AIDS epidemic by 2030. At the conference UNAIDS director Michel Sidibé stressed how important continued funding is if we are to achieve this target. However, as the varied results from these test-and-treat trials show, funding is necessary but not sufficient; it is also vital to devise programmes that actually meet the prevention and treatment needs of people which, as SAPPHIRE shows, may or may not include PrEP.
US now has at least 80,000 on PrEP: first thousand on French programme
Nearly 80,000 people in the US have started Truvada for PrEP over the past four years, according to the latest results from a survey of retail pharmacies presented at Durban. The number starting per quarter rose eightfold between 2012 and 2015. Nearly a quarter (24%) were women, who tended to be younger. The state with the highest proportion of PrEP users was Massachusetts, with one PrEP user per 1370 inhabitants. This compares with an HIV prevalence of 1 per 340. Experts agree that this may underestimate the total number of PrEP users, meaning the true number of users could now be up to 150,000.
Among PrEP users with ethnicity data, white people made up 74% and African Americans 10%: while African Americans form 12% of the US population, they account for 44% of new HIV diagnoses.
Meanwhile, up to July 2016, 1077 people, 96% of them gay men, have started PrEP through the public programme in France that began in November. Two-thirds have opted to take PrEP intermittently in accordance with the regimen used in the Ipergay trial; two pills in the 24 hours before sex and one each on the two days afterwards; the other third took it daily.
Ipergay finally closed in June. There were in total three infections in 734 patient-years on PrEP in the study and 14 infections in 212 patient-years on placebo. This means that the HIV infection rate in people on PrEP was 97% lower than it was in people on placebo. This is despite the fact that only 50% of sex acts were covered by at least two doses of Truvada, and 31% of blood samples showed no evidence of PrEP use in the last month. There was a significant difference in sexual behaviour between the randomised and open-label phases of the trial. During the randomised phase, the proportion who used condoms during their last intercourse varied between 25% and 40% while during the open-label phase it decreased significantly from 23% to 14%. The percentage of participants who were diagnosed with at least one sexually transmitted infection in a person-year was 35% in the randomised phase and 41% in the open-label phase.
Comment: Such high effectiveness in Ipergay despite 50% usage can only mean that participants were correctly judging their HIV risk and tailoring their PrEP use to it. But evidence is accruing that once people know they are definitely on PrEP, levels of condom use can decrease further and sexually transmitted infections can increase. Given that PrEP is now becoming firmly established in the US and pressure for its adoption elsewhere continues, there should be a conversation about reframing condom messaging within sexual health strategies that include PrEP. If ‘safer sex’ is now a broader concept than just using condoms, which aspect of it do condoms still fulfil best?
Studies look at PrEP in black and young gay men
A US trial has shown that high levels of PrEP use can be achieved in a demonstration project for black men who have sex with men, if its recruitment and support structures are tailored to their needs. Previous studies such as ADAPT have found lower uptake of and adherence to PrEP in black men who have sex with men than in other groups, and particularly in young men.
The HPTN073 “My Life, My Health, My Choice” study was too small, with 226 participants, to demonstrate a statistically significant reduction in HIV cases. Nonetheless, HIV incidence was 62% lower in men electing to take PrEP during the study than the minority who never did. Eight weeks into the trial, two-thirds of men had drug levels consistent with taking four or more doses of PrEP a week; at the end this was 56%.
Meanwhile, the ATN 113 or Project PrEPARE trial looked at young men who sex with men aged 15 to 17. Of 260 deemed eligible for the study, more than half declined to participate. In the end 79 enrolled, though 32 discontinued the study prematurely. Over the course of the study three young men had acquired HIV, meaning an annual HIV incidence of 6.41% – among the highest rates ever seen in a PrEP programme. Adherence was initially quite good, with a majority of participants achieving protective tenofovir levels during monthly visits, but it decreased after they switched to every three months. More than half of the participants had highly protective levels of drug (at least four doses per week) during the first three months, but this dropped to one-third after they switched to quarterly follow-up.
Comment: A frustrating aspect of PrEP is that those who need it most – which in the US means young and black gay men – take it least. HPTN 073 offered, alongside PrEP, a multidisciplinary support system, and awareness raising and support training was given to anyone “at the table” in the trial, ranging from physicians to volunteers. As for ATN113, although it demonstrated that PrEP is safe for young users, its main lesson is that we have not yet found a similar structure to encourage adolescents to take PrEP, despite the need being clearly there. Both recruitment and adherence findings show that gay teens need a lot of support.
Other recent news headlines
Strong association between sexual violence and African women acquiring HIV in Europe
Migrant African women who have acquired HIV since moving to France are four times more likely to have experienced forced sex in France than other migrant women, researchers reported at Durban. The study suggests that sexual violence is an important risk factor for migrant women acquiring HIV while living in Europe.
Stigma persists in the undetectable era
In an era of widespread HIV treatment and undetectable viral load, stigma remains a persistent feature in the lives of almost half of people living with diagnosed HIV in the UK, according to findings from The People Living with HIV Stigma Survey UK 2015 reported at Durban. Compared with white British or Irish participants, people of other ethnicities experienced greater problems with disclosure and discrimination.
Far fewer people drop out of HIV care in South Africa than previously thought
Previous research has considerably over-estimated the number of people living with HIV who stop attending medical facilities in South Africa. Previously, people who stopped attending one clinic were assumed to have dropped out of care entirely. A new analysis shows that nine years after beginning therapy, just 17% were still attending their original clinic but 54% were still in care somewhere in the health system.
Australia adopts ambitious plan to use PrEP to ‘virtually eliminate’ HIV by 2020
Australia plans an ambitious programme of pre-exposure prophylaxis (PrEP) provision for gay men at high risk of HIV, with the aim of ‘virtually eliminating’ HIV in the gay community by 2020. The PrEP roll-out is initially in the form of scientific implementation studies conducted by at least three Australian states. This enables state governments to subsidise the drug costs despite a refusal from the federal government to pay for PrEP – see story below. The New South Wales programme was launched under the name of EPIC-NSW in March, and the programme in Victoria, under the name PrEPX, in June. One in Queensland is due to start soon.
Editors' picks from other sources
Gilead ignored HIV groups before failed bid to have PrEP subsidised In Australia
from Buzzfeed
A drug manufacturer failed to take the advice of top HIV/AIDS organisations when it made a submission for a highly effective HIV prevention drug to be subsidised by the government, those organisations say.
European Commission grants marketing authorisation for Gilead’s once-daily Truvada for reducing the risk of sexually acquired HIV
from Gilead Sciences Press Release
The European Commission has granted marketing authorisation for once-daily Truvada in combination with safer-sex practices to reduce the risk of sexually acquired HIV infection among uninfected adults at high risk.
The end of the end of AIDS
from the World Bank blog
The Durban 2016 AIDS Conference marks the end of "ending the HIV epidemic" as a feasible goal with the tools we have. We need new and better tools. Talk of ending AIDS has led to a widespread perception in the broader health and development community that this crisis is over. It isn't.
Nurse-led PrEP clinic in San Francisco shares model of success at AIDS 2016
from BETA blog
A programme by the San Francisco AIDS Foundation uses a nurse-led model of care to provide free, easy-to-access PrEP services to cisgender and transgender men who have sex with men. Thus far, there have been zero new HIV infections among people in the PrEP programme, and this includes people who miss visits and return after four to five months. Two acute HIV infections were detected at study enrolment. There have been 82 HIV infections in the clinic – among people not on PrEP – since the PrEP Health Program launched.