Emergence of Multiclass Drug–Resistance in HIV‐2 in Antiretroviral‐Treated Individuals in Senegal: Implications for HIV‐2 Treatment in Resouce‐Limited West Africa
Open Access
- 15 February 2009
- journal article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 48 (4), 476-483
- https://doi.org/10.1086/596504
Abstract
Background. The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HIV-2 that confer ARV resistance are not well characterized. Methods. Twenty-three patients were studied as part of an ongoing prospective longitudinal cohort study of ARV therapy for HIV-2 infection in Senegal. Patients were treated with nucleoside reverse-transcriptase inhibitor (NRTI)– and PI (indinavir)–based regimens. HIV-2 pol genes from these patients were genotyped, and the mutations predictive of resistance in HIV-2 were assessed. Correlates of ARV resistance were analyzed. Results. Multiclass drug–resistance mutations (NRTI and PI) were detected in strains in 30% of patients; 52% had evidence of resistance to at least 1 ARV class. The reverse-transcriptase mutations M184V and K65R, which confer high-level resistance to lamivudine and emtricitabine in HIV-2, were found in strains from 43% and 9% of patients, respectively. The Q151M mutation, which confers multinucleoside resistance in HIV-2, emerged in strains from 9% of patients. HIV-1–associated thymidine analogue mutations (M41L, D67N, K70R, L210W, and T215Y/F) were not observed, with the exception of K70R, which was present together with K65R and Q151M in a strain from 1 patient. Eight patients had HIV-2 with PI mutations associated with indinavir resistance, including K7R, I54M, V62A, I82F, L90M, L99F; 4 patients had strains with multiple PI resistance–associated mutations. The duration of ARV therapy was positively associated with the development of drug resistance ( P=.02 ). Nine (82%) of 11 patients with HIV-2 with detectable ARV resistance had undetectable plasma HIV-2 RNA loads (10 copies/mL), compared with 3 (25%) of 12 patients with HIV-2 with detectable ARV resistance (P=.009). Patients with ARV-resistant virus had higher plasma HIV-2 RNA loads, compared with those with non–ARV-resistant virus (median, 1.7 log>10 copies/mL [range, 10 copies/mL] vs. 10 copies/mL [range, 10 copies/mL]; P=.003 ). Conclusions. HIV-2–infected individuals treated with ARV therapy in Senegal commonly have HIV-2 mutations consistent with multiclass drug resistance. Additional clinical studies are required to improve the efficacy of primary and salvage treatment regimens for treating HIV-2 infection.This publication has 41 references indexed in Scilit:
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