Smith, C; Cambiano, V; O'Connor, J; Nakagawa, F; Lodwick, R; Rodger, A; Lampe, F; + view all Smith, C; Cambiano, V; O'Connor, J; Nakagawa, F; Lodwick, R; Rodger, A; Lampe, F; Phillips, A; - view fewer (2012) Evaluating HIV treatment as prevention in the European context. European Centre for Disease Prevention and Control: Stockholm.

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Abstract

Executive summary The goal of this project is to gather evidence regarding the population-level, and to some extent, individual-level effects of the use of antiretroviral treatment (ART) to prevent HIV infection, and to relate this to current HIV treatment guidelines. To inform the project, formal literature reviews were performed for the three main areas of interest: the effect of antiretroviral therapy in adults on preventing sexual transmission of HIV, prevention of mother-to-child transmission (pMTCT) and post exposure prophylaxis (PEP). The strongest evidence with regard to the effect of treatment of HIV positive individuals to prevent onwards sexual transmission comes from the recent randomised controlled trial (RCT), HPTN052. This study demonstrated that early versus delayed ART led to a 96% relative reduction in onwards linked transmission. Several observational studies of HIV sero-discordant heterosexual couples have also reported that transmission is rare in patients on ART, particularly in those with low HIV-RNA concentrations. However, the findings of HPTN052 and these observational studies are mainly applicable to vaginal heterosexual sex. No direct empirical evidence regarding the relationship between ART use and the risk of HIV transmission through anal intercourse is currently available. Whilst the major HIV treatment guidelines do not explicitly recommend prescribing antiretroviral treatment to prevent onwards transmission, they do not rule out individuals starting ART at a high CD4 count on a case-by-case basis. However, one must also consider the impact of earlier treatment on the HIV positive individual with regard to side effects, and development of drug resistance. Early studies showed that pMTCT regimens containing a single antiretroviral agent (short course zidovudine or single dose nevirapine) or two antiretroviral agents (zidovudine and lamivudine with or without single dose nevirapine) led to clinically important reductions in MTCT rates. However, the most substantial reductions in MTCT rates occurred when combination antiretroviral regimens (more than three antiretroviral drugs) were introduced. These regimens involve the receipt of ART before the third trimester of pregnancy, intrapartum treatment, maternal post-partum treatment and some form of neonatal treatment. There is some evidence from RCTs and extensive evidence from observational studies of the efficacy of these combination regimens, with very low rates of transmission of around 0% to 6%, in settings with no or very little breastfeeding, and 1%-9% when breastfeeding occurs. Furthermore, in settings where avoidance of breastfeeding is not possible, there are a number of studies demonstrating that receipt of maternal and/or neonatal ART during the six months after birth can reduce the risk of perinatal transmissions. All treatment guidelines recommend that HIV-positive pregnant women should receive ART to prevent MTCT, although the exact timing of when ART should begin is not always explicit. Furthermore, where mentioned, use of neonatal ART is also recommended, regardless of whether infants are breastfed. Much of the data supporting the use of PEP are based on animal models, which suggest that PEP is most efficacious if commenced as soon as possible after exposure. When considering occupational exposure to HIV, human studies are limited, as no RCTs exist for ethical reasons. Evidence for efficacy is based on one case control study which demonstrated an 81% reduction in transmission of HIV through the use of zidovudine. Other studies have demonstrated that PEP following occupational exposure is not always effective and there are cases of PEP failure. Similarly, there are also no RCTs assessing the efficacy of PEP for prevention of HIV transmission after sexual exposure, and limited evidence from observational data. Most treatment guidelines agree that PEP is not always effective and PEP policies need to emphasise the importance of risk prevention in the first place in all settings where there is a risk of HIV transmission. Side effects are not uncommon when using PEP, so it is important to consider carefully whether an individual should receive PEP and some studies have suggested that increase in availability of PEP may lead to an increase in risky sex behaviour. Antiretroviral treatment has well documented benefits in reducing transmission of HIV and, in particular, has had a major population level impact on HIV acquisition in children from HIV positive mothers. Further research is needed to help us understand how we can best use ART to prevent HIV infections through other transmission routes, and to develop evidence-based policy recommendations, particularly in the European context.

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