Key Factors Influencing the Emergence of Human Immunodeficiency Virus Drug Resistance in Low- and Middle-Income Countries

Abstract

The emergence and spread of human immunodeficiency virus (HIV) drug resistance from antiretroviral roll-out programs remain a threat to long-term control of the HIV-AIDS epidemic in low- and middle-income countries (LMICs). The patterns of drug resistance and factors driving emergence of resistance are complex and multifactorial. The key drivers of drug resistance in LMICs are reviewed here, and recommendations are made to limit their influence on antiretroviral therapy efficacy.

Keywords: HIV subtype; HIV-1 drug resistance; antiretroviral therapy failure.

Figure 1.

Overview of mutations linked to first-line failure. Generally, the first mutation to develop is the M184V mutation linked to 3TC/FTC exposure, followed concurrently by nonnucleoside reverse transcriptase inhibitor mutations at a rate of an additional 1 mutation for every 3 months on a failing regimen and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations. The NRTI mutation patterns depends on the NRTI used. Mutations circled in red have been associated with subtype C. Abbreviations: 3TC, lamivudine; AZT, zidovudine; d4T, stavudine; EFV, efavirenz; FTC, emtricitabine; NNRTI, nonnucleoside reverse transcriptase inhibitor; NVP, nevirapine; TAMs, thymidine analog mutations; TDF, tenofovir.