HIV This Week

Van de Vijver DA, Derdelinckx I, Boucher CA. Department of Virology, Erasmus MC, University Medical Centre Rotterdam, and 2Department of Medical Microbiology, University Medical Centre Utrecht, the Netherlands. Circulating HIV type 1 drug resistance will have limited impact on the effectiveness of preexposure prophylaxis among young women in Zimbabwe. J Infect Dis. 2009;199(9):1310-7.

Preexposure prophylaxis (PrEP) with antiretroviral drugs may prevent transmission of human immunodeficiency virus (HIV). The objective of van de Vijver and colleagues was to predict whether PrEP, in the presence of circulating drug resistance, will reduce the risk of infection with HIV. They used risk equations to calculate the monthly risk of infection with HIV before and after the introduction of PrEP.  Uncertainty and sensitivity analyses were performed for 2 ranges of PrEP effectiveness (40%-60% and 60%-80%). Circulating drug resistance was assumed to reduce the effectiveness of PrEP by 50%-90% and the transmissibility of HIV by 0%-30%. Parameter ranges were chosen for women 17-29 years of age from publications on HIV in Manicaland in Zimbabwe. PrEP would decrease the median risk of HIV transmission by 21%-33% (effectiveness of PrEP, 40%-60% and 60%-80%). If 50% of HIV strains are drug resistant, then the median risk reduction would be 19%-26% if drug-resistant strains were less transmissible than wild-type HIV and 12%-19% if they were equally transmissible. The risk would increase if condoms were frequently replaced with PrEP. Use of PrEP for sexual acts for which no protection is currently used would be beneficial. The public health impact of PrEP will depend on its effectiveness and on risk behaviour. Circulating drug resistance will have only a small impact on the effectiveness of PrEP.

Editors’ note: As this mathematical modelling shows, the precise impact of PrEP will depend on many factors such as its effectiveness (which remains to be determined by clinical trials in humans), the prevalence of condom use, the frequency with which condom use is replaced by PrEP when it becomes available, the number of sex acts performed, and the level of PrEP use among individuals currently not using condoms. Most discussion of drug resistance in relation to PrEP has focused on the extent to which PrEP use might create drug resistance. Interestingly, this model looked at the impact on PrEP of various levels of circulating M184V, the mutation resistant to emtricitabine or FTC. The model predicts limited impact of population-level drug resistance on PrEP’s contribution to HIV prevention, assuming that resistant virus is less fit.

Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, Bennet and colleagues outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 reverse transcriptor and protease mutations meeting these criteria (surveillance drug resistance mutations). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, the authors follow the same procedures described previously to develop an updated list of surveillance drug resistance mutations that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated surveillance drug resistance mutation list has 93 mutations including 34 non-nucleoside reverse transcriptase protease inhibitor-resistance mutations at 15 reverse transcriptor positions, 19 non-nucleoside reverse transcriptase protease inhibitor-resistance mutations at 10 reverse transcriptor positions, and 40 protease inhibitor-resistance mutations at 18 protease positions.

Editors’ note: Population-based surveillance of transmitted drug resistance in recently infected individuals is a cornerstone of optimal treatment programmes. This WHO updated list of surveillance drug mutations is not designed to be used for individual patient management. Rather, its value lies in the fact that it permits accurate estimation of transmitted resistance as well as comparison of estimates of transmitted resistance from different regions and times.