US public health department recommends PrEP

The US Centers for Disease Control and Prevention (CDC) has released new guidelines recommending that pre-exposure prophylaxis (PrEP) should be considered for anyone HIV-negative who has a sexual partner with HIV.

The guidelines also recommend PrEP for any gay man who has had a sexually transmitted infection (STI) or who has had sex without a condom in the last six months, any non-gay person who has had condomless sex in the last six months with someone at high risk of HIV, or anyone who in the last six months has injected drugs and shared equipment. While the CDC recommends that the benefits of condom use are also explained, especially to people with inconsistent PrEP adherence, they do not say that condoms should be provided alongside PrEP or that PrEP and condoms should be used together.

The US Food and Drug Administration (FDA) approved the use of Truvada (tenofovir plus emtricitabine) as PrEP in 2012, but did not make recommendations as to who should be considered for PrEP. The CDC issued previous guidelines in July 2011, but these were only for gay men, did not go into detail about who should be offered PrEP other than that they should be at “substantial risk”, and mandated condom distribution alongside PrEP.

Comment: The New York Times in an article commented that the CDC's recommendations "could transform AIDS prevention in the United States". However, the attitudes of healthcare workers and the willingness of health insurance funders to pay for PrEP will be key to any expansion of what is still not a widely used prevention method.

Impossible to rule out risk of infection from someone on treatment

Although the chance that someone on fully suppressive HIV therapy could pass HIV on to their (heterosexual) partner may be zero, it may never be possible to demonstrate this, French scientists have said recently. The scientists found four cases where someone had transmitted HIV to their opposite-sex partner in 1672 couples, in studies which did tests to prove that the newly diagnosed partner’s infection actually did come from their partner, not someone outside the relationship. Three of these infections occurred within the HIV-positive partner’s first six months on therapy and all four within a year. The researchers calculate that, if couples had unprotected sex six times a month consistently for ten years, the maximum likely risk of infection would be 1.85% if all four infections happened within the first six months or 3.7% otherwise. The minimum likely risk would be zero. This is compatible with another US study which calculated a ten-year risk of 2%, though this is an average risk rather than a maximum-likely risk. The risk for gay men could not be calculated by either study. It is also important to note that neither study calculated the risk of transmission from someone with an undetectable viral load, so may include cases of treatment failure.

Comment: It is important to note that the percentages quoted – which are probably at the upper end of the true risk – may change as we acquire more knowledge of the effectiveness of treatment as prevention from studies like PARTNER, and in particular of the risk via anal sex.

HIV infection on PrEP will probably not cause drug resistance

People who acquire HIV despite taking pre-exposure prophylaxis (PrEP) will probably not have drug-resistant HIV as a result, researchers from the iPrEx study say. In this groundbreaking trial of PrEP, the only cases of drug resistance involved people who had unrecognised acute HIV infection when they started therapy. None of the 48 people in the study who acquired HIV despite being randomised to take PrEP had resistance mutations or reduced sensitivity to one of the two drugs in Truvada, tenofovir. In two trial participants, a very low proportion of their HIV – less than 1% – had resistance to the other drug, emtricitabine, but this is unlikely to affect the success of subsequent treatment.

Comment: This is good news for people worried that the use of PrEP, especially inconsistent use, will seed a new wave of drug resistance. Modelling studies based on the South African epidemic have indicated that the amount of resistance generated by PrEP should be 13-16 times lower than the amount generated by treatment for HIV.

STI diagnoses much higher in people not taking HIV treatment

Sexually transmitted infection (STI) rates are much higher among people living with HIV before they start antiretroviral therapy (ART) than after they start it, a study from South Africa shows. The study looked at 1465 people who started ART in Cape Town between 2009 and 2011. Women made up 65% of the sample and the mean age was 33 years. The study period covered an equal amount of time before and after participants started ART. No less than 88% of the STIs people contracted were diagnosed before they started ART, the other 12% occurring while they were on treatment, meaning that STI rates were seven times higher in the period before the study participants started HIV therapy than afterwards. The true burden of STIs may even have been higher, as many infections will have been asymptomatic. The researchers adjusted for factors such as the number of sexual partners people had and the number of clinic visits, but still found that STI incidence for people off ART was nearly twice what it was for people on it. STIs were 70% higher in men and twice as high in people under 35 than in people over that age.

Comment: Exactly why people with HIV not taking ART had double the rate of STIs is not clear from this study. It could be better medical monitoring, the effects of age, or that people taking ART tended to be sicker (people with low CD4 counts had few STIs). There might also be some direct effect from HIV drugs against some viral STIs like herpes. An untreated population with a high incidence of STIs may be one explanation why treatment as prevention does not always seem to reduce HIV incidence, as the STIs increase the risk of HIV being passed on.

Tenofovir as PrEP causes no long-term harm to kidneys

HIV pre-exposure prophylaxis (PrEP) using tenofovir is associated with mild disturbances in kidney function that resolve when treatment is stopped, a study has found. This was the conclusion reached by researchers investigating kidney function in people who inject drugs who took tenofovir as PrEP in a study in Thailand that reported last year. In this study, taking daily tenofovir halved the risk of HIV infection. The study is significant as participants took tenofovir for longer than in other PrEP studies – up to five years. Participants were monitored at twelve-month intervals and changes in kidney function were compared between the 1204 people taking tenofovir and the 1209 on placebo pills. The definition of kidney dysfunction used was creatinine clearance below 50ml/min: 3.7% of people taking treatment had this compared to 2.2% of those on placebo, and creatinine clearance was lower in years two to five of the study. A significant decline in mean creatinine clearance was observed in the treatment arm but not in people in the placebo arm. Follow-up of participants who stopped taking tenofovir at the end of the study showed that disturbances in kidney function associated with tenofovir were temporary and had resolved a median of 20 months later.

Comment: This should be relatively reassuring for people worried about the risk of this side-effect in people taking tenofovir or tenofovir/emtricitabine (Truvada) as PrEP. Although taking tenofovir does lead to a continuous but very slow decline in kidney function compared to people of similar age not taking it, the difference is not huge and severe effects are rare and appear not to be permanent. 

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