the Netherlands. Circulating HIV type

the Netherlands. Circulating HIV type 1 drug resistance will have limited impact on the effectiveness of preexposure prophylaxis among young women in Zimbabwe.

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.