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

Clinical infectious diseases, 2009-02, Vol.48 (4), p.476-783 [Peer Reviewed Journal]

2009 by the Infectious Diseases Society of America 2009 ;2009 INIST-CNRS ;Copyright University of Chicago, acting through its Press Feb 15, 2009 ;2009 by the Infectious Diseases Society of America. All rights reserved. 2009 ;ISSN: 1058-4838 ;EISSN: 1537-6591 ;DOI: 10.1086/596504 ;PMID: 19143530 ;CODEN: CIDIEL

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Title:
Emergence of Multiclass Drug–Resistance in HIV-2 in Antiretroviral-Treated Individuals in Senegal: Implications for HIV-2 Treatment in Resouce-Limited West Africa
Author: Gottlieb, Geoffrey S. ; Badiane, Ndeye Mery Dia ; Hawes, Stephen E. ; Fortes, Louise ; Toure, Macoumba ; Ndour, Cheikh T. ; Starling, Alison K. ; Traore, Fatou ; Sall, Fatima ; Wong, Kim G. ; Cherne, Stephen L. ; Anderson, Donovan J. ; Dye, Stefanie A. ; Smith, Robert A. ; Mullins, James I. ; Kiviat, Nancy B. ; Sow, Papa Salif
Subjects: Adult ; Amino Acid Substitution - genetics ; Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiretroviral drugs ; Antiretroviral Therapy, Highly Active - methods ; Antiviral agents ; Biological and medical sciences ; Drug resistance ; Drug Resistance, Viral ; Drug therapy ; Female ; HIV ; HIV Infections - drug therapy ; HIV Infections - virology ; HIV Reverse Transcriptase - genetics ; HIV-2 - drug effects ; HIV-2 - isolation & purification ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Male ; Medical sciences ; Middle Aged ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Patients ; Pharmacology. Drug treatments ; Phylogeny ; Senegal ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral Load
Is Part Of: Clinical infectious diseases, 2009-02, Vol.48 (4), p.476-783
Description: 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 (<1.4 log>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, <1.4 to 2.6 log>10 copies/mL] vs. <1.4 log>10 copies/mL [range, <1.4 to 1.6 log>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.
Publisher: Oxford: The University of Chicago Press
Language: English
Identifier: ISSN: 1058-4838
EISSN: 1537-6591
DOI: 10.1086/596504
PMID: 19143530
CODEN: CIDIEL
Source: MEDLINE
Alma/SFX Local Collection

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

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