The recent Conference on Retroviruses and Opportunistic Infections (CROI) in Boston in the US was one of the most interesting and productive for a long time, with a particularly rich crop of news about HIV prevention strategies ranging from trials of innovative pre-exposure prophylaxis (PrEP) and microbicides to vast community-wide trials of HIV treatment as prevention.
The stories below only represent a minority of the news from this conference, which also contained news on hepatitis and TB treatment and prevention, HIV cure research, novel HIV treatments, and global health. For all our news reporting from CROI, visit: www.aidsmap.com/croi-2016.
French PrEP trial: half only used PrEP, a quarter condoms and PrEP, one in six neither
The researchers from the French Ipergay trial of intermittent pre-exposure prophylaxis (PrEP) presented data on condom and PrEP use during the trial.
They found that just over half of men in the Ipergay study used PrEP frequently but rarely used condoms; about a quarter had high levels of both PrEP and condom use; and one in 16 preferred to use condoms and rarely used PrEP. However, this left about one in six trial participants who had low levels of use of both PrEP and condoms. Some of this group never took much PrEP – but in a minority, PrEP use declined as the study went on.
A second presentation of results from the open-label phase of the study, when all participants knew they were on PrEP, found that the use of condoms where the participant was the receptive partner declined slightly but significantly, with a relative 15 to 20% fall from previous condom use rates.
There was one more HIV infection during the open-label study but this participant confirmed he had not used PrEP for at least six weeks. Over the whole study, there were 94% fewer infections in people given PrEP than in ones given a placebo.
Comment: This analysis confirms that the majority of men participating in the placebo-controlled phase of Ipergay were already infrequent users of condoms, and that their overall protection from HIV was enhanced by PrEP (if they were in the Truvada arm of the study). The fall in condom use in the open-label phase is not large, but it is significant. The important thing to do is to address the needs of the one in six participants who used neither condoms nor PrEP, who tended to be older, have more depression, and more anonymous sex.
High levels of chemsex and injecting in HIV-positive gay men in English clinics
A survey of 532 HIV-positive gay men attending clinics in England and Wales found that 29% reported engaging in ‘chemsex’ (defined by the researchers as “the use of drugs to increase disinhibition and sexual arousal”) in the past year and that one in ten reported ‘slamsex’ (injecting – or being injected with – the drugs). Figures were higher for some subgroups: 37% of Londoners reported chemsex and nearly one in five (19%) of men on antiretroviral therapy (ART) reported slamsex.
Chemsex users were more likely to be middle-aged rather than young: 34% of men aged 35-54 reported it. It was reported by 38% of men also reporting depression or anxiety, and 39% of men who smoked.
Chemsex and slamsex users were six times less likely to report always using condoms, and reported a lot more partners – on average 30 in the last year versus 9.5 in men who did not have chemsex. The odds of reporting a sexually transmitted infection (STI) were three to four times higher in men reporting chemsex or slamsex. They were more than six times more likely to have ever had hepatitis B or C and men who had slamsex were more than nine times more likely.
Comment: These figures are astoundingly high, particularly for injecting. They should result in demands for a completely new approach, both within the NHS and the gay community, to supporting gay men’s sexual and emotional health, particularly those with HIV.
Almost-certain case of PrEP failure due to drug resistance reported
A man in Toronto, Canada, became infected with a multidrug-resistant strain of HIV despite apparently consistent adherence to PrEP, the conference heard.
The man had been on PrEP for two years and appeared to have good adherence on the basis of the frequency of pharmacy refills. In April 2015, his regular HIV and STI test showed he had acute HIV infection. He was adamant that he maintained excellent adherence to PrEP.
A test was taken 20 days after he was diagnosed that measures drug levels inside red blood cells. In these, levels rise much more slowly, so it can detect a recent period of poor adherence. Drug levels in the patient’s red blood cells were actually 47% higher than the average figure, showing likely consistent PrEP adherence for the period covering his exposure to HIV.
A drug-resistance test showed that he had HIV with complete resistance to emtricitabine and moderate resistance to tenofovir (the two drugs in Truvada). It also, very unusually, was resistant to some of the integrase inhibitor drugs, especially elvitegravir (a component of Stribild).
Comment: On the balance of probabilities this is probably the first documented case of the failure of Truvada PrEP despite high adherence and more-than-adequate drug levels (though recently two cases of failure on solo tenofovir were published). It is not unexpected that there would be occasional cases of PrEP failure; but the fact that this is the first case report among the tens of thousands of people now taking PrEP shows that it is very rare.
People with HIV considerably overestimate their chance of infecting someone
Only a small proportion of HIV-positive people in a large US treatment study regarded themselves as non-infectious after three years on antiretroviral therapy (ART), and more than half regarded their risk of infecting others as substantial, even though only 10% had a detectable viral load, the conference was told. There was no correlation between a person’s actual viral load and their belief about how infectious they were.
People were asked the question “How likely would you be to give someone HIV if you had unprotected sex with them today?”
As the start of the study, 58% thought they were highly infectious, and 26% placed themselves in the “medium” category. This left 16% who thought – at this point inaccurately – that their risk of infecting another person was “low” (10%) or zero (6%).
After nearly three years on HIV treatment, over a third still thought they were highly infectious and a majority (52%) thought they were highly or somewhat infectious. Another third thought their chances of infecting someone were low, and 14% thought it was zero.
The trial finished around the time that the PARTNER study, which found no transmissions from anyone with an undetectable viral load, announced its interim findings; if the same question was asked today people’s beliefs about their infectiousness might be different.
Comment: Knowledge of the facts about viral load and transmission can only help people with HIV, by relieving them of anxiety about infecting others and relieving others of fear of people with HIV. Unfortunately, eight years after the Swiss Statement first said, essentially, that ‘undetectable is uninfectious’, there is still opposition to wider public dissemination of this message. This tends to come from clinicians who are confused about the difference between a message about the virus – that if it’s not detectable, you can’t get it – and a message about the patient, namely that such a state depends on full adherence.
Major disparities persist in lifetime risk of HIV diagnosis in the US
The lifetime risk of being diagnosed with HIV in the US has decreased overall during the past decade, from about one chance in 78 during 2004-2005 to one in 99 during 2009-2013, the conference heard. The number of HIV diagnoses and deaths between 2009 and 2013 were used to calculate the probability of an HIV diagnosis at a given age.
However, the risk varies widely amongst different groups. Men who have sex with men have a one in six chance of ever being diagnosed – nearly 80 times more likely than heterosexual men, and over 400 times the risk in white heterosexual men who have never injected drugs. And black gay and bisexual men had the highest risk of any subgroup, with one in two expected to be diagnosed over a lifetime.
Comment: This study, along with the PrEP failure case, got the most media attention of any at the conference. It was only an updating of figures that epidemiologists already knew, but using lifetime risk is a particularly stark way of showing how unequal the risk of HIV is between certain groups, and adds to the social justice argument for measures like PrEP and treatment for all on diagnosis.
Expanding treatment and PrEP could prevent 185,000 new HIV infections, US CDC says
Better care for people living with HIV in the United States could lead to a large decrease in HIV transmission, preventing some 185,000 new infections by the year 2020, a new model says. The impact of PrEP would be comparatively modest, but its importance would be greater if more people with HIV were not on treatment.
The model looked at what would happen if 61% of all the HIV-positive people in the US had an undetectable viral load. At present, only 26 to 30% of people in the US have an undetectable viral load. The model also looked at the benefit of PrEP used by 40% of high-risk men who have sex with men (MSM), 10% of people who inject drugs and 10% of high-risk heterosexuals.
They predicted that increasing the number of people on ART with undetectable viral load would, by itself, prevent more than 168,000 new infections by 2020 and adding PrEP to that would prevent 17,000 more. If diagnosis and treatment rates remained stable at 2015 levels, expanded use of PrEP alone could potentially prevent 48,000 new infections.
Comment: This quantifies the relative contribution of testing, treatment and PrEP and shows that relatively achievable treatment and PrEP targets – in the case of the treatment targets, ones already reached by a number of other countries – could reduce HIV infections in the US by no less than 70% by 2020.
Vaginal rings moderately effective – but not in the youngest women
The results of two studies, ASPIRE and the Ring study, announced at the conference, show that vaginal rings impregnated with an anti-HIV drug were effective at cutting the HIV infection rate in women.
However, the overall effectiveness seen was only moderate, preventing less than a third of infections that would otherwise have happened. The primary reason for this was that the rings had no effect at all in the youngest trial participants, aged 18 to 21 – who also had the highest rates of HIV infection. The rings were more effective in older women with almost two-thirds of infections prevented in women over 25 in one of the two studies.
These poorer-than-expected results could be caused by a combination of intrinsic efficacy of less than 100% in the rings, intermittent use among participants (who tended to take them out for cleaning, especially during their period or during sex), and greater vulnerability to HIV infection among young women.
Whether these are the reasons for the relatively low levels of adherence and lack of effect seen in young women, remains to be seen. The same is true of whether these results will be enough for the ring to be licensed as a protection method.
Comment: In a way these results were the worst possible because they don’t tell researchers and regulators what to do next: whether to stop vaginal ring development, at least with this drug, or move ahead with roll-out. Open-label extensions of both trials have now got the funding to move ahead, however, and these may provide us with clearer answers.