February 2015

Gay men’s project in Russia and Hungary boosts condom use: may have brought down HIV rate

The success of a peer-recruited gay men’s prevention programme in St Petersburg in Russia and Budapest in Hungary has shown that it is possible to involve gay men in HIV prevention activities in hostile environments.

The study started with a core group of 18 gay men/men who have sex with men (MSM) who were identified by researchers as having a particularly large number of diverse social contacts in the local MSM population. They recruited others who in turn recruited others, so that eventually 626 men were recruited into the 18 groups (averaging 35 members). Although all men received a basic counselling and education session in HIV prevention tactics at the start of the study – when they also received testing for HIV and sexually transmitted infections (STIs) – about 30% also received training, via role plays, in how to discuss HIV risk and prevention with friends and acquaintances.

The average age of participants was 28 and some (7.2%) were living with HIV. When risk behaviour was measured a year after the end of the programme, there was a sustained 20% fall in the number of men who had condomless sex in the study; a 50% fall in condomless sex with casual and non-regular partners (from 18% to 9%); and a threefold fall in sex with multiple partners, from 14% to 5%.

In contrast, no indicator of sexual health risk declined among a control group of men who had received the initial tests and short information session, but did not take any part in the peer-recruited training project.

The study was too small to establish statistically significant falls in HIV and STI incidence. Nonetheless, HIV incidence in the intervention arm was 3% in the year following the study, but 5% in the control arm and STI incidence 5% versus 8%.

Comment: This study not only shows that HIV prevention work can be done in hostile environments, it also shows that traditional models of HIV prevention based on peer education can still produce positive behaviour change in areas where gay men may never previously have had access to reliable HIV prevention support at all.

US researchers publish estimate of condom effectiveness in anal sex

The US Centers for Disease Control and Prevention (CDC) has published a paper that found that condoms used consistently stop seven out of ten HIV infections acquired through anal sex between men. Overall condom effectiveness was 70.5% and where the HIV-negative partner was the receptive partner, 72.3%.

This analysis (originally presented at a conference in 2013) does not establish the efficacy of condoms under ideal conditions, and it is likely that condoms used both 100% consistently and 100% correctly are more efficacious than this. But it does establish the likely effectiveness of typical condom use, by comparing HIV incidence in gay men who said they had always used condoms during the previous months, with HIV incidence in men who said they had never used them during the same period.

The 70.5% is actually the mean of the efficacy found in two different US studies. Although these studies took place 14 to 17 years ago, none since have the features that make it possible to estimate condom effectiveness. One, VAX 004, was an HIV vaccine study and the other, EXPLORE, the study of a behavioural intervention. In both cases they were large and collected data on condom use and HIV status longitudinally at six-month intervals during the study; most similar studies are unable to relate condom use to HIV incidence so closely. In EXPLORE, condom effectiveness was 86%, and in the VAX 004 study it was 61%. This difference is interesting (see comment below), but it is also interesting that the mean value agrees with the only other study of condom effectiveness in anal sex, conducted back in 1989, which also found an effectiveness of 70%.

The CDC analysis finds two other things. Firstly, condom use had virtually no effect among the group who said they ‘sometimes’ used condoms – at most, a 25% reduction where the HIV-negative partner was receptive. However, that does not mean that 100% condom use is the only effective strategy: it means that, because ‘sometimes’ use was not stratified, there is a point, as yet undetermined, between always using them and never using them where intermittent use becomes ineffective as a strategy.

Secondly, it found that only one in seven – 13% – of men were able to maintain 100% condom use over the whole three-year study period surveyed, or 20% when they were the receptive partner. Equally, only 4.4% of the men never once used a condom during the entire three years. So inconsistent condom use was the most consistent behaviour over the long term.

Comment: There is actually no statistical difference between the 70% effectiveness found in this analysis and the 80% effectiveness figure found in meta-analyses of condom effectiveness in heterosexuals/in vaginal sex. It is important to re-emphasise that this is not a study of the maximum likely efficacy of condoms, which is clearly higher, but the likely ‘real world’ limit to their effectiveness, given that people do not always find them easy to use. Regarding why condom effectiveness was different in the two studies analysed, the CDC paper controls for differences between study populations, so this does not explain the difference: it is possible that, as a behavioural intervention, EXPLORE taught some of its participants better condom-use skills or, alternatively, made reporting not using a condom less stigmatising. This would mean real usage would not be overstated, so effectiveness would appear to be greater.

HIV is becoming more virulent over time in Europe

A study of nearly 16,000 white gay men with HIV, largely in western Europe, has found that the average length of time between infection and CD4 count falling below 350 cells/mm3 has halved over the last 25 years, from seven years to 3.4 years. It also found that the average CD4 count immediately after the acute phase of HIV infection fell by 200 cells/mm3, from 770 cells/mm3 to 570 cells/mm3, between 1979 and 2002, and that during the same period the average post-acute viral load rose from 11,200 copies/ml in 1980 to 31,000 copies/ml.

These data come from CASCADE, a cohort study of patients largely in western European countries (though some patients in Australia and Canada were also included). The researchers only looked at white gay male patients because female and non-white patients were likely to have a much more diverse treatment history and because European gay men nearly always have subtype B of HIV and virulence varies between subtype.

This apparent increase in the virulence of HIV over time has considerable implications for HIV testing policy and treatment guidelines – both because people now have a shorter time window in which to get diagnosed and linked to care before they need to go on treatment, and possibly because increases in the average viral load may mean people not on antiretroviral therapy are more infectious. The researchers calculate that the increase in viral load implies a 44% increase in the average infectiousness of untreated gay male European patients in CASCADE.

These data appear to contradict data from a smaller but more widely reported study that found that HIV virulence appeared to have decreased over time in two locations in South Africa and Botswana. These findings may not be in conflict, as HIV evolves very rapidly to fit local circumstances. In a heterosexual epidemic with few people on treatment, HIV needs to ‘ensure’ that the people it infects survive long enough to pass it on to others: in a faster-spreading epidemic with more people on treatment, it is in the interests of viral survival for it to become more rapidly passed on, before people start taking treatment. These differing evolutionary pressures may drive HIV virulence in opposite directions.

Comment: The southern African study was published in a journal just before World AIDS Day and was widely reported, by the BBC among others. These reports seemed not to appreciate two things. Firstly, viral evolution is rapid: a change in viral ‘fitness’ in one direction may suddenly be reversed as evolutionary pressures change. Secondly, just because virulence is falling in one part of the world does not mean it is falling elsewhere: this is a bit like saying that, because rhinos are endangered in southern Africa, foxes must be in Europe. The change toward greater virulence in Europe seems to have somewhat stabilised since 2002, but the time between infection and a CD4 count below 350 cells/mm3 is still falling in gay men, reinforcing the importance of frequent testing in this population.

Most HIV in gay men passed between younger, undiagnosed partners who know each other

A modelling study based on the latest update of HIV infections in the UK has found that two-thirds of HIV infections are transmitted by men who do not know that they have HIV, and 85% by men who are not taking treatment. However, the study found that only about 10% of HIV is passed on by people who are in the acute phase of HIV infection, when they have a very high viral load but may not test positive on a standard HIV antibody test. This is because the acute phase only lasts a few weeks.

The study also finds that HIV is rarely passed on through completely casual or anonymous sex. Ninety per cent of infections occur between partners who know each other, either as a primary partner or as a regular ‘sex buddy’. However, most transmissions originated in men who had two or more new partners within a year. This would imply that most infections occur in pairs of men who may have a succession of short relationships or, more likely, several simultaneous regular sexual partners.

Although the majority of gay men living with HIV in the UK are 35 or older, the model found that 62% of transmissions originate in men aged below 35.

“The majority of new HIV infections among [men who have sex with men] in the UK is…accounted for by a small group of highly sexually active individuals under 35, living with undiagnosed HIV in the asymptomatic stage”, comment the researchers.

Comment: Younger gay men, especially, need to be encouraged to test more often, to disclose or test together within any kind of steady relationship, and not to assume that lack of evidence of HIV-positive status is evidence of HIV-negative status.

Gay men are better at predicting when they won’t have sex than when they will

One of the most important HIV prevention results from last year was the high effectiveness found in the French IPERGAY study of pre-exposure prophylaxis (PrEP) (see last bulletin).

Although detailed results will not be presented until the Conference on Retroviruses and Opportunistic Infections (CROI) in February, we already know that this will be the first PrEP study to demonstrate the effectiveness of a non-daily regimen: IPERGAY participants took a double dose of tenofovir/emtricitabine (Truvada) 2-24 hours before they thought they were likely to have sex and then, if they actually did, took a single dose on each of the following two days. Participants in the IPERGAY study ended up taking 50% of the pills they would have taken if they had been on daily PrEP (and had good adherence), so this underlines the potential cost-savings that could accrue from intermittent PrEP.

This strategy clearly depends on people being able to predict when they will have sex. A study from New York, in which gay men who largely had sex with casual partners kept ‘sex diaries’ and also predicted whether they would have sex the following day, found that in general men had sex less often than they predicted. When they predicted that there was a 100% likelihood they would have sex the following day, only 58% did. Their predictions only matched reality on the days when they predicted there was ‘no chance’ of their having sex the following day.

The researchers suggest that an intermittent-PrEP regimen like IPERGAY might be safer and easier to use if it was tied to not having sex, rather than having it: “Take PrEP unless you are certain you are not going to have sex the following day” rather than “Take PrEP if you think you will have sex”.

Generalising from the study findings, they found that, in the latter case, while only 20% of PrEP doses taken would actually be needed, 3.8% of occasions would also be uncovered by PrEP because sex had not been anticipated.

Comment: We will find out more, hopefully, at CROI, when at least some of the PrEP-taking behaviour of IPERGAY participants may be presented (though this will be hard to analyse in practice). Another study called ADAPT (HPTN 067), which looks at two other intermittent-PrEP regimens, is also due to report soon.

The most effective HIV prevention method for teenage girls in Africa? Keep them in school.

A study from Rakai province in Uganda has found that 71% of an eightfold decline in HIV incidence in young women aged 15 to 19 is due to young women starting sex later – a phenomenon the researchers attribute entirely to a higher proportion of young women attending school. The other 29% is due to fewer infections occurring in young women who have already started having sex.

A previous analysis had found that if school attendance for young women was evaluated as an HIV prevention method, its effectiveness would be 78%.

This is particularly crucial because HIV incidence and prevalence in teenage girls in Africa tends to be much higher than among teenage boys, and if these peak-incidence years could be delayed, the overall rate of HIV infection in the population might decrease.

The proportion of 15- to 19-year-old girls attending school increased from 26% to 59% between 1999 and 2011, and annual HIV incidence declined during the same period from 1.7% to 0.2% in this age group. At the same time, the proportion of adolescent girls who had ever had sex declined from 76% to 50%.

Of note, although school attendance and age at first sex also increased in adolescent boys, it was only in young girls that the declines in HIV incidence were seen: essentially, education abolished the disparity in the age at which girls acquired HIV so that both sexes had peak HIV incidence in their 20s.

Comment: This study confirms what had long been suspected. The effects seen do not seem to be due to better sex education, nor to condom use; more likely, school education empowered young women both to say no to sex and to negotiate risk when they had it. A recent qualitative study from Rakai found that, compared with young people who remained HIV-negative, ones who acquired HIV had “relationships marked by poorer HIV-related communication, greater suspicion and mistrust, and larger and more transitory sexual networks”. The primary cause of the increase in adolescent school attendance, in both sexes, was the decision by the Ugandan Government in 2007 to abolish school fees and introduce universal secondary education, as they had done for primary education ten years earlier.

Other recent news headlines

Substance use and social problems predict HIV infection in American gay men

American gay men reporting depression, childhood sexual abuse, stimulant use, other substance use and heavy alcohol use are nine times more likely than men without any of these issues to subsequently acquire HIV, according to the findings of a large study conducted over four years. The EXPLORE study – the same study mined for data on condom effectiveness in the report above – related HIV acquisition to participants’ reporting of depression, sexual abuse in childhood and drug and alcohol use. It found that HIV incidence was five times higher in men who reported three out of a list of five problems (depression, sexual abuse in childhood, and ‘party drug’ use, polydrug use, and heavy alcohol use) and nine times higher in men reporting all five issues. Only 25% of men reported no such problems.

No new HIV infections seen in US PrEP programme

No new HIV infections have occurred among more than 500 users of the Kaiser Permanente healthcare provider system in San Francisco in members using pre-exposure prophylaxis (PrEP). However, condom use appears to be declining among a subset of gay men, according to a small survey presented last December. Among the 90 men who have so far answered a behavioural survey – a group that may not be representative of Kaiser's PrEP users overall – half said their condom use had remained the same, 45% said it had decreased, and 5% said it had increased since they started PrEP. "PrEP is provided for the purpose of preventing HIV infections, and we're seeing that hold true," said Bradley Hare, Kaiser's San Francisco director of HIV care and prevention. "We don’t know if [condom use] went from 100% to zero, or from 50% to 40%," he added. “[But] with the extra protection provided by PrEP, some may have decided to forego condoms."

US guidelines on prevention with people living with HIV now emphasise engagement with care, HIV treatment and social factors

The US Centers for Disease Control and Prevention (CDC) has published new recommendations on HIV prevention for people who are HIV positive. The CDC last issued guidelines on what is sometimes called ‘prevention with positives’ in 2003 and mainly concentrated on how to encourage condom use and help people with HIV avoid risk behaviour. The new guidelines – at 240 pages, ten times longer than the 2003 guidelines – take greater account of social and structural factors as well as the profound impact that antiretrovirals have on HIV transmission. For example, an individual may need support with poverty, mental illness, substance use or unstable housing in order to be able to fully engage with medical care and adhere to HIV treatment, they comment.

Russia may face shortage of anti-AIDS drugs in 2015

from EATG

Russia may face a shortage of anti-AIDS drugs in 2015 due to the current complex situation in the national economy and devaluation of the rouble, according to recent statements of Vadim Pokrovsky, head of the Russian Federal Research and Methodological Center for Prevention and Control of AIDS. This year, the Ministry of Health plans to allocate about 22.6 billion roubles (US$ 500 million) on the purchase of new drugs against HIV. However, according to analysts’ estimates, these funds will be not enough to compensate for the ever growing shortage of these products in the domestic market.

European advocates engage with biomedical prevention

from AVAC

On January 22-25, the European AIDS Treatment Group and AVAC organised an unprecedented three-day workshop: New Developments in HIV Prevention. In addition to comprehensive updates on product pipelines across the prevention research landscape, the group discussed the anticipation of the first data from European oral PrEP trials and the implications for PrEP access in Europe. See the EATG/AVAC Tumblr for presentations and photos from the workshop. The workshop was organised by Gus Cairns of NAM.

HIV sweeps across eastern Europe amid economic crisis

from EUobserver

HIV is spreading at a dangerous rate in nations around the Black Sea, passing a record 100,000 new cases yearly. Hotspots for the HIV rise are Ukraine and Russia – two countries facing economic crisis and armed conflict, factors which could provoke a further surge in the virus.

Ukrainian drug users dying due to treatment ban, says UN

from The Guardian

As many as 100 drug users in Crimea may have died since the peninsula was annexed by Russia, according to a top United Nations official, due to the substitution therapy they were receiving from Ukrainian authorities being illegal under Russian law.

China reports sharp rise in HIV cases in 2014

from Financial Times (free registration required)

China has reported a sharp rise in new cases of HIV infection last year, highlighting increased incidence of the disease among the elderly and young students. Official media reported a 15% rise in the number of people diagnosed with HIV last year over the previous year, with about 100,000 people newly infected in 2014.

Long-acting drug effectively prevents HIV-like infection in monkeys

from Rockefeller University press release

Two new studies, including one conducted by researchers at the Aaron Diamond AIDS Research Center (ADARC) and Rockefeller University, published in Science Translational Medicine, show that long-acting cabotegravir injections are highly protective in a monkey model of vaginal transmission of a virus similar to HIV. This study was first reported by Aidsmap last year. A study in humans in now underway.