Antiretroviral Therapy and Pre-exposure Prophylaxis: Combined Impact on HIV Transmission and Drug Resistance in South Africa

(See the editorial commentary by Celum et al on pages 189–91) Oral antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is a new biomedical intervention against human immunodeficiency virus (HIV) transmission with proven efficacy [1–3]. There is concern, however, about the potential emergence and spread of HIV drug resistance arising from the rollout of PrEP, particularly in resource-constrained settings, where antiretroviral therapy (ART) options are limited [4]. This concern is amplified by the possibility that the same ARVs will be used for both ART and PrEP. The combination of 2 nucleoside reverse-transcriptase inhibitors, tenofovir (TDF) and lamivudine or emtricitabine (3TC or FTC, respectively), with 1 nonnucleoside reverse-transcriptase inhibitor (NNRTI), efavirenz or nevirapine, is the World Health Organization–recommended first-line ART regimen in several countries worldwide, including South Africa [4], and TDF or TDF + FTC have shown efficacy in HIV prevention trials [1–3]. Thus far, only 9 drug-resistant cases have been observed among clinical trial participants on PrEP, most of whom had unrecognized acute infection at enrollment. However, clinical trials of PrEP are not designed to address the population-level and/or long-term epidemiological impact of PrEP, including consequences of drug resistance. We therefore used a mathematical model [5] to examine the potential impact of orally administered overlapping and nonoverlapping PrEP and ART on HIV transmission and drug resistance in South Africa.