Emergence of Multiclass Drug–Resistance in HIV-2 in Antiretroviral-Treated Individuals in Senegal: Implications for HIV-2 Treatment in Resouce-Limited West Africa

HIV-2 infection is endemic in West Africa, but unlike HIV-1 infection, it has had limited spread worldwide [1]. Compared with HIV-1 infection, HIV-2 infection is characterized by a much longer asymptomatic stage, lower plasma viral loads, slower decrease in CD4 cell count, decreased mortality rate associated with AIDS, and lower rates of genital tract shedding, mother-to--child transmission, and sexual transmission [1–5]. Nonetheless, a significant proportion of HIV-2 infections eventually progress to AIDS, and HIV-2–infected individuals may benefit from antiretroviral (ARV) therapy [3, 6]. ARV therapy is becoming increasingly available in West Africa, where HIV-2 infects up to 1–2 million people [7]. As ARV therapy “scale-up” programs proliferate in West Africa, significant numbers of HIV-2–infected individuals will have access to and will be treated with ARV drugs developed against HIV-1 infection [8]. However, HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide, and reports suggest that HIV-2 may be partially resistant to some protease inhibitors (PIs) and has a low genetic barrier to nucleoside reverse-transcriptase inhibitor (NRTI) resistance [9–12]. To date, there have been no randomized clinical trials of ARV therapy for HIV-2 infection [13]. However, several small observational cohort studies in developed countries have shown poor outcomes of ARV therapy for HIV-2 infection [14–16]; similar poor results were reported in 3 small studies from resource-limited settings in Senegal, The Gambia, and Cote d'Ivoire, West Africa [17–19]. To assess the emergence of reverse-transcriptase (RT) and protease (PR) resistance mutations that occur in virus strains during ARV therapy among a cohort of HIV-2–infected individuals in Senegal, West Africa, we sequenced pol genes from plasma samples and PBMCs obtained from a cohort of ARV-treated persons participating in the Senegalese Initiative for Access to Antiretrovirals (ISAARV) program.