UK PrEP study completes enrolment

The pilot stage of the PROUD study – the UK's study of HIV pre-exposure prophylaxis (PrEP) in gay men – is now fully enrolled, having reached its target of 550 participants by the end of April. The trial investigators have applied for funding to expand PROUD into a full-scale efficacy trial with 2300 participants. A final decision on this is expected in November, meaning that any expansion will not start recruiting until spring 2015.

PROUD is a two-year study with participants randomised either to take Truvada daily for two years or to take it only during the second year. The aim of deferring PrEP for half of the participants for a year is that, because it is not a placebo-controlled trial and all those taking PrEP will know they are on active drug, the trial can take a true measurement of whether people change their sexual risk behaviour once they know they are taking PrEP.

The first data – on the baseline characteristics of participants – was released at the Third Joint Conference of BHIVA (British HIV Association) with BASHH (British Association for Sexual Health and HIV) in April. The average age of the 443 participants with data was 35.5 years with a quarter of them were aged 29 or below. Eighty per cent of participants were white and nearly 60% were graduates. Participants reported a median of ten anal sex partners in the last three months and used condoms with half to three-quarters of partners. A third of participants’ partners were known to have HIV but at least 80% of these were on HIV treatment.

Participants were asked why they didn’t use condoms when they didn’t. Most gave several different reasons but the most common reason was “It’s much more enjoyable without a condom” (given by two-thirds of participants. No fewer than 40% of participants had used post-exposure prophylaxis (PEP) in the 12 months before joining the study and 21% had used it more than once.

PROUD participants reported high levels of drug use: half had used mephedrone or similar, 43% GHB, 35% cocaine and 24% methamphetamine.

Expanded HIV testing may find more acute infections as well as late ones

Expanding HIV testing into local hospitals and primary care may not only find more people who have lived with HIV for a long time without knowing it, but may also find more people who have only recently acquired HIV, a pilot study from Vancouver in Canada has found

A pilot project evaluating a programme of expanded HIV testing took place between October 2011 and June 2013. This involved instituting routine HIV testing for all admissions to the three acute care hospitals serving Vancouver and also routine testing of patients in primary care: in the latter case over 500 primary care physicians signed up to the pilot scheme.

The scheme resulted in an expansion of tests in hospitals from about 500 a month before October 2011 to 2500 a month in October 2012, and an expansion of tests in primary care from 650 a month during 2011 to 2000 a month in the first half of 2013. There were over 73,000 tests performed in the last six months of the pilot compared with 38,000 in any six-month period in 2008-10.

The number of people diagnosed with HIV in hospitals doubled during the pilot, from 11 in 2010 to 30 in 2012 and 27 in 2013. While the 0.2% of people diagnosed in primary care, and in hospital outpatients, roughly matches the prevalence of HIV in the general population in British Columbia, the proportion diagnosed in hospital admissions was 0.5%.

As expected, the hospital pilot picked up on considerably more late presenters: the proportion of people diagnosed with a CD4 count below 200 cells/mm3 was 35%, compared with 12% in other centres. However, and unexpectedly, it also detected more people in the acute stage of infection: these formed 25% of the total, compared with 15%.

This may be because people with acute HIV may not suspect their symptoms have anything to do with HIV, especially if they have recently tested negative.

'Chemsex' not common in London gay men; more so in men with HIV

A recent report from London finds that the use of drugs such as crystal methamphetamine, mephedrone and GHB/GBL during sex (so-called ‘chemsex’) was still a minority behaviour even in the London boroughs of Lambeth, Southwark and Lewisham, which have the highest concentration both of gay men and of men with HIV of any part of the UK.

A recent analysis of figures from the large EMIS (European MSM Survey) study found that 1142 men from these London boroughs had answered the survey. Of these, approximately 10% had used mephedrone or GHB/GBL in the last month and 5% had used crystal meth – and these drug use figures were about double those in gay men in other parts of London.

Only 3.5% of men had injected any drug in the last year. However, two-thirds of those who had injected drugs were men living with HIV, as were more than two-thirds of those taking crystal meth, implying that, in this area, as many as one in five men with HIV might be injecting and one in four taking crystal meth.

One in ten men were concerned about their drug use. In contrast, 93% of men drank alcohol – the most popular drug of all – and 25% were concerned about their drinking.

In qualitative interviews with 30 men who had had ‘chemsex’ in the past year, one-third of them living with HIV, 30% (nine men) reported injecting drugs, but all reported safe injecting practices. Men split roughly into three groups: men living with HIV who had taken a decision to have condomless sex with other HIV-positive men (serosorting), although they sometimes assumed the HIV status of partners rather than ascertaining it; a group of largely HIV-negative men who in the main maintained non-risky sexual practices despite using drugs; and a group of men who did feel they were not in control of the risks they took when intoxicated.  

Although the figures show that ‘chemsex’ is still a minority pursuit in gay men, it is associated with significant health impacts. Another recent report from London, where UK-acquired cases of the serious gut infection shigella have increased 8-fold since 2005, largely in gay men, found that a third of a group of 42 gay men recently diagnosed with the bug reported injecting drugs and three-quarters reported recreational drug use. Nearly 60% had HIV and 88% had not heard of shigella until they got it.

Shigella can cause severe diarrhoea, and 30% of those diagnosed had gone to hospital emergency departments because of their symptoms. Four individuals were admitted to hospital. Shigella can be cured with antibiotics.

HIV diagnoses in French gay men up 14%, mainly due to more testing

Recent data from France show that 2600 gay men there were diagnosed with HIV in 2012. This 14% increase on the previous year is far larger than the long-term rate of increase in diagnoses, which had been rising at about 3% a year since 2003.

Diagnoses have not been rising in heterosexual people; there were 3500 heterosexual cases diagnosed in 2012, half of them in people born in sub-Saharan Africa.

Although there is clearly ongoing transmission among gay men, a large proportion of the increase is due to more testing, public health officials said. Incidence assays showed that 47% of gay men were diagnosed within a few months of their infection in 2012, up from 42% in 2011 – a sign of more frequent testing. It is estimated that 29% of all individuals living with undiagnosed HIV in France acquired their HIV in the last year.

Another study has estimated that 83,000 people acquired HIV in France between 2000 and 2010 and that 29,000 of those (35%) remain undiagnosed. It is estimated that nearly 3% of gay men, 0.6% of people who inject drugs, 0.4% of non-French native heterosexuals and 0.03% of French-born heterosexuals has HIV.

HIV genital viral load: undetectable in women on treatment, can vary hourly in men

One unresolved issue in HIV prevention science is what level of viral load in genital fluids indicates infectiousness and whether low but detectable viral load in genital fluids is predictive of transmission.

Two studies recently have, if anything, added to the complexity of data in this field.

Previous studies have suggested that viral load in women’s genital secretions may be more likely to remain detectable even if HIV is undetectable in their blood, than is the case in men.

A US study recently has found the opposite: in a study of 20 non-pregnant, pre-menopausal women on one particular combination therapy (tenofovir, emtricitabine and boosted atazanavir: Truvada plus Reyataz with Norvir) while viral load above 50 copies/ml was measurable in 10.6% of 123 blood samples, it was not detectable at that level in any sample of cervico-vaginal fluid.

The researchers used a sensitive test that could in fact detect much lower levels of HIV genetic material than this; while this test detected HIV in 59% of blood samples, it could only find it in 16% of vaginal samples.

Another study in men provided quite different results. In this, French scientists found that HIV was detectable in 7.5% of semen samples from men with no detectable HIV in their blood. The average seminal viral load was 705 copies/ml and in 3.6% of all samples it was over 1000 copies/ml.

There was a nearly significant difference in the likelihood of detectable HIV in semen according to HIV treatment regimen. In men taking protease inhibitor-based therapy, HIV was detectable in 29% of samples compared with 7.7% on regimens based on other drug classes.

Some men were able to provide two different semen samples within an hour. In 9% of these pairs of samples, HIV was detectable in one sample (average viral load 918 copies/ml) but not the other.

The authors cite a figure of 0.03% (one transmission in 3333 occasions of sex) for the likelihood of transmission from a man with a seminal viral load of 1000 copies/ml, although the recent PARTNER study found no transmissions from an HIV-positive person on treatment in 44,000 episodes of anal and vaginal sex.

Taiwan harm reduction programme cuts HIV in drug users by 80%

Implementation of a comprehensive harm reduction programme has successfully contained the HIV epidemic among people who inject drugs in Taiwan.

In 2004, estimated HIV incidence among prisoners with a history of drug use in Taiwan was 6.44%. Incidence peaked at 18% in 2005. The introduction of the large-scale harm reduction programme was accompanied by a sharp fall in incidence. In 2007, it had fallen to 2%. Incidence was just 0.27% in 2010.

Community viral load also declined among prisoners, from a mean of 93,000 copies/ml in 2006 to a mean of 11,710 copies/ml in 2010. The proportion of people with a viral load below 1000 copies/ml increased from 21% in 2006 to 40% in 2010.

The annual HIV incidence rate among former prisoners who received methadone maintenance therapy was 0.165% compared with 1.33% a year among former prisoners who did not receive this therapy. After controlling for potential confounders, the investigators found that engaging with methadone maintenance programmes reduced the risk of infection with HIV by 80% and there was a zero HIV incidence rate among frequent users of needle and syringe exchanges. This compares to an incidence rate of 0.5% among people who inject drugs who did not use such services.

Total HIV prevalence among people who inject drugs in Taiwan increased substantially between 2004 and 2006. The increase slowed between 2007 and 2009, and fell slightly in 2010.

Rwanda cuts HIV incidence by 90% as it goes for universal HIV treatment

The achievement of high rates of HIV treatment in one African country, Rwanda, has resulted in HIV diagnoses more than halving and annual incidence falling by 90%, the 2014 Treatment as Prevention workshop in Vancouver heard last month.

It is estimated that, in Rwanda, as of this year, 93% of people living with diagnosed HIV with CD4 counts below 350 cells/mm3 are on antiretroviral therapy (ART), 59% of all people diagnosed with HIV, and about 40% of everyone with HIV, diagnosed and undiagnosed. The median CD4 count at diagnosis is now 300 cells/mm3.

HIV treatment coverage is still patchy, with some centres reporting 80% coverage of all diagnosed people and others only 20%; one particularly challenging area is the slums on the outskirts of the capital, Kigali.

About 37,000 people tested positive for HIV in 2007: by 2011 diagnoses were down to 23,000 and last year they declined to 13,000. This is despite the number of HIV tests going up, and would be even more dramatic if it reflected true incidence: annual incidence of HIV in fact declined nearly tenfold from 0.25% a year in 2004 to 0.03% in 2012.

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Giving treatment to specific high-risk people may bring down HIV faster

The number of people someone with HIV infects during their life can vary by five orders of magnitude, the 2014 Treatment as Prevention Workshop heard last month. This figure, called the reproduction number, or R0, determines whether an epidemic grows or shrinks: if it is over 1, the epidemic will grow. A close analysis of the epidemic in one province in Vietnam, where HIV is rather evenly spread around risk groups (female sex workers, people who inject drugs and gay men) as well as being present in other women who often acquire HIV from partners who have been with sex workers. The R0 of different population groups ranged from 99 in sex workers who also injected drugs to 0.06 in sex-worker clients. It was found that if HIV treatment was in limited supply, the most efficient treatment-as-prevention strategy would be to preferentially give it to people who inject drugs as they are connected to most other risk groups.

Can we provide point-of-care viral load tests in poor countries?

In the next two years it may become possible to provide portable, non lab-based viral load tests for low-income countries that cost little more than CD4 counts, the 2014 Treatment as Prevention Workshop heard. With more people being treated earlier even in poorer countries, it is more important to find out if treatment is suppressing the virus. Manufacturers’ costs per portable viral load test are currently 67% higher than lab-based tests because they cannot use disposable components like reagents in bulk. The actual price charged to African countries for viral load tests including all equipment averaged around US$25 per test for lab-based tests and would be at least US$33 for portable tests, but this could be brought down to US$12 per test if samples were pooled. This is not too much more expensive that the per-test cost of a CD4 count – about US$7.50.

Annual HIV tests for high-risk groups could have a big impact on UK's HIV epidemic

A testing programme targeting high-risk groups that was combined with one-off screening for other adults would prevent between 4 and 15% of future infections in the UK, a study has found. The model predicted that without a scale-up of HIV testing, annual HIV incidence would remain unchanged in the UK at about 3500 new infections per year. If annual testing of high-risk groups was instituted along with a one-off national screen it would prevent up to 23% of future infections. There would be 15,000 new HIV diagnoses in the first year compared with the 6100 diagnosed in 2013. This targeted testing approach with one-off testing for others, would provide 80% of the benefits of a universal HIV test for the whole population, but at only 14% of the cost over ten years.