What’s happening in PrEP?
Although we have now known for two years that pre-exposure prophylaxis (PrEP), in which HIV-negative people take antiretroviral drugs in order to protect themselves from HIV, has been shown to be highly effective in gay men, heterosexual people and for serodiscordant couples, there are still many questions about its practicality and its generalisability. Another study, for instance, found it did not work as an option for young South African women.
It is, however, cost that may be the biggest barrier to the widespread use of this new method of HIV prevention. A recent mathematical study, based on the data from Peruvian sites in the iPrEX study in gay men, found that PrEP could be quite cost effective: in Peru, the price of an extra year’s worth of HIV-free life came out at US$140 to $1400, depending on how carefully targeted PrEP was. Even so, the absolute costs of PrEP would mean that, at present drug prices, a country such as Peru could not afford a large enough programme to make a big dent in HIV infections there.
There are a number of trial PrEP programmes happening at present, but the four most important studies, designed to find out more about its potential, are:
ADAPT (HPTN 067): This six-month study compares taking Truvada (tenofovir/FTC) as PrEP daily, twice weekly or the day before anticipated sex, with another dose two hours after sex in the latter two groups. In Cape Town, 180 women are already enrolled; enrolment in Thailand of 180 gay men and other men who have sex with men (MSM) and transgendered people (TG) started in September; and a second MSM/TG group is planned for New York.
IPERGAY: This two-year French study compares Truvada, taken 24 hours before and two hours after sex, with a placebo. At present, it is in a pilot phase at three sites, with just over 100 enrolled so far. It is hoped eventually to expand the trial to 2000 gay men. There has been some controversy about whether the placebo arm should continue, though on 1 October the study’s scientific committee decided it should be continued for now.
PROUD: This is a UK study, due to start in mid-November. Its primary aim is to discover if taking PrEP changes other sexual risk behaviours such as using condoms, which has always been a concern. In the pilot phase, 500 gay men will all receive an intensified programme of safer-sex support, with half being offered Truvada PrEP immediately, and the other half starting it a year later. If this pilot study seems feasible, it is hoped to expand it to a large 5000-strong study.
NEXT-PrEP (HPTN 069): This one-year study uses a new HIV PrEP drug, maraviroc (Celsentri). It started in July and will enrol 400 gay men and 200 women at twelve sites in the US. They are split into three groups, which will take either maraviroc plus tenofovir and FTC placebo pills; maraviroc and FTC plus tenofovir placebo; or maraviroc and tenofovir plus FTC placebo.
Results are expected in late 2013 for ADAPT and mid-2014 for NEXT-PrEP; results for the other two depend on whether their pilot phases will be expanded.
Methadone maintenance halves HIV risk
Opiate substitution therapy (OST) for people who inject drugs using methadone reduces the risk of HIV infection by at least 40%, according to the results of a systematic meta-analysis. On the other hand, using methadone as a detox drug to wean people off opiates entirely was associated with a greater risk of HIV infection.
The investigators also searched for studies of OST using buprenorphine, but did not find any fitting the meta-analysis criteria.
Twelve published and three unpublished studies of methadone maintenance therapy (MMT), published between 1992 and 2009, were identified, of which nine were sufficiently similar to have their results pooled. Six of these studies were from north America, two from Europe (London and Amsterdam), and one from Thailand. Three of the studies also included methadone detoxes. There were 819 new HIV infections with an annual incidence of 3.5%.
Overall, MMT reduced incidence by 54%; in the six studies that adjusted for confounders, it reduced it by 40%. There was no evidence that the benefits of OST differed by region or were affected by the provision of incentives to people. However, there was a weak association between longer duration of substitution therapy and greater benefit in terms of reduced HIV incidence: in the Amsterdam study, which had by far the longest follow-up period (20 years), MMT reduced HIV infections by 60%.
In contrast, when methadone was used for detoxification rather than maintenance, the risk of HIV infection was actually 54% greater than baseline incidence.
“These data further support calls for the global increase of harm reduction interventions to reduce the transmission of HIV between people who inject drugs and between [them] and the wider community,” the researchers comment.
Viral load no defence in Norway
It retains HIV exposure without transmission as an offence and says that giving assent to the risk of unprotected sex would only be legally valid if witnessed by a healthcare worker in order to establish truly informed consent.
The commission’s conclusions disappointed a coalition of HIV activists, which had hoped that an examination of the law would lead to the commission restricting HIV transmission prosecutions to clearly deliberate ones, as has happened in some nearby countries such as the Netherlands and Denmark. The latter suspended prosecutions under its own criminal code last year.
The commission says that using condoms would be a defence regardless of other risk factors such as the HIV-positive person’s viral load. This contradicts the recent judgement of the Canadian Supreme Court, which said that condom use alone was not a sufficient defence as there was still a “realistic possibility” of infection: only in cases where the HIV-positive person also had an undetectable viral load would sex without disclosure be no crime.
The Norwegian commission, by contrast, does not regard undetectable viral load as a valid defence, asserting: “The knowledge available about the risk of infection…with an HIV-positive person under medical treatment remains too uncertain [to conclude that unprotected sex would not be an offence]”. It does, however, say that an undetectable viral load might be taken into account during sentencing.
Louis Gay, the Norwegian activist who is publicly fighting a prosecution for a single case of oral sex without disclosure – which, ironically, might not be indictable under the proposed new legislation – simply commented: “Welcome to my world.” Indicted in March, Gay’s trial has now been postponed because his complainant – whose HIV has been shown not to come from Gay – has left the country.
More Africans infected in UK than thought
A new method uses CD4 cell counts and the year a person arrived in the UK to estimate when they were infected, rather than relying on people’s own views on when and where it happened.
The proportion of UK-acquired infections in the African population has been going up and, in the last year investigated (2010), stood at 43%.
Previous research has suggested that people can be more at risk of HIV when they emigrate to another country, even if their home country has high prevalence; studies suggesting this have been conducted in African and Caribbean migrants to the Netherlands, Central and Eastern European gay migrants to the UK and Mexican migrants to the United States.
Is treatment as prevention working in France?
It has been theorised for some time that if a big enough proportion of the HIV-positive population was on treatment, a point would be reached where HIV infections would decline as fewer people would have a detectable HIV viral load.
Some studies of gay men in San Francisco, injecting drug users in Vancouver and heterosexual people in parts of South Africa suggest that reducing the average viral load of HIV-positive people may be having an effect on HIV incidence there. But until now there has been no evidence of it happening in Europe.
In the French study, the proportion of people who had been on antiretroviral therapy for at least three months rose from 70% in 2005 to 85% in 2010. During that time, CVL – defined as the sum of the most recent viral loads from each person in any one year – declined from 79.5 million in 2005 to 57.5 million in 2010 – statistically significant.
The decline in CVL was a modest 28%, despite a nearly 60% increase in the absolute number of people on treatment in the five years. This is probably, the researchers comment, because many infections are arising from the estimated 30% of people with HIV in France who are undiagnosed.
Another study from Geneva in Switzerland supports this idea. Genetic analysis of infections in people diagnosed between 2008 and 2010 found that two-thirds of them belonged to new genetically related clusters of infections, and 41% belonged to clusters exclusively composed of people diagnosed during these same two years. In contrast, only 8% had been infected by people who appeared to have acquired HIV before 2000.
Scots take up HIV testing
Between 2000 and 2010, the proportion reporting a test in the last twelve months increased from 27 to 57%. The proportion of men who had ever tested for HIV rose from 50% in 2000 to 80% in 2010.
There was also an increase in the proportion of men who perceived testing as beneficial and as a community norm.
The investigators believe their results point towards the “normalization” of HIV testing.
“These changes, which were independent of both demographic factors and sexual behaviour, represent a key change in HIV-related health behaviour akin to the profound changes in condom use noted during the 1980s.”
Other recent news headlines
Massive increase of hepatitis C incidence in HIV-positive gay men in Switzerland
Incidence of hepatitis C virus (HCV) infections has increased 18-fold in HIV-positive gay men in Switzerland since 1998. Half of all infections occurred between 2008 and 2011. In contrast, incidence of hepatitis C remained stable in HIV-positive heterosexuals and fell in HIV-positive injecting drug users (IDUs). HCV incidence is now higher in gay men than amongst IDUs.
Grindr smartphone app could be a good way to recruit gay men to HIV prevention studies
Gay men can be effectively and efficiently recruited to HIV prevention studies using the Grindr smartphone app, US researchers find. Grindr was especially useful for reaching younger, more educated gay men with a higher number of sexual partners.
More evidence that rapid ‘combination’ test often fails to detect acute HIV infection
A rapid, point-of-care test, which aims to reduce the ‘window period’ through the detection of both antibodies and p24 antigen, performs poorly in a UK clinical setting. While the Determine HIV-1/2 Ag/Ab Combo reliably identified people with HIV antibodies, it delivered false-negative results to most people who had very recent HIV infection.
Progression of anal neoplasia is common among gay men with HIV
HIV-positive gay men with anal lesions caused by human papillomavirus (HPV) progress to anal cancer at a worrying rate, a Spanish study has found. Scientists found that one in 300 gay men with so-called high-grade squamous intraepithelial lesions (HSIL) progressed to anal cancer within a year, as did one in 500 with low-grade lesions (LSIL). Progression from LSIL to HSIL was extremely common, happening in 40% of cases.
Editors’ picks from other sources
Pre-exposure prophylaxis for HIV prevention – polling results
A poll in the New England Journal of Medicine found that its readers are split 50/50 on whether pre-exposure prophylaxis (PrEP) is a good idea. The journal posed cases of a 46-year-old gay man and an 18-year-old African woman who were both having unprotected sex and asked if readers would prescribe PrEP. Fifty-one per cent said yes for the gay man and 49% for the young woman.
Human papillomavirus vaccine could prevent thousands of cancers and genital warts
US sexual health experts have urged that more teenage girls receive the Gardasil vaccine against human papillomavirus (HPV), some strains of which can cause genital warts and cervical, anal and some oral cancers. Despite FDA approval for national vaccination in teenage girls aged 13 to 17, the vaccine, which is 100% effective at preventing the four main types of HPV if given before sexual debut, was only given to 32% of girls compared with 84% in the UK last year. The US has, however, approved Gardasil vaccination for boys, which so far the UK has failed to do.
Drug ‘shooting galleries’ to be tested by France
French health minister Marisol Touraine has recommended a pilot of injection rooms, so-called ‘shooting galleries’, where drug users can inject in sterile, medically supervised conditions rather than on the street. If the French parliament approves this scheme, trials could start in December. A handful of countries, including Germany and Switzerland, already run shooting galleries.
Magic Johnson to be new face of HIV home-testing kit
HIV activist and former basketball player Earvin ‘Magic’ Johnson has agreed to be the public face of a campaign to promote use of over-the-counter HIV home-testing kits in the US. With the Food and Drug Administration-approved test, Americans will be able to use a mouth swab and get results in 20 minutes. OraQuick will be available at pharmacies and online for US$40. HIV testing kits are not approved for over-the-counter sale in Europe.
My life on PrEP
A gay HIV prevention worker in LA, writing under the name Jake Sobo, launches an honest and sexy blog about his decision to start taking PrEP to protect himself from HIV, and how this has affected decisions he makes about his sex life.