title: Virological response and resistance profiles after 24 months of first-line antiretroviral treatment in adults living in Bangui, Central African Republic.
abstract: The rate of virological failure was assessed in 386 adult patients attending the Centre National Hospitalier Universitaire of Bangui, the capital city of the Central African Republic (CAR), receiving their first-line antiretroviral (ARV) drug regimen for 24 months, according to the World Health Organization (WHO) recommendations. In addition, genotypic resistance testing was carried out in 45 of 145 randomly selected patients whose plasma HIV-1 RNA load was detectable. Overall, 28.5% of ARV-treated patients were in virological failure (e.g., HIV-1 RNA >3.7 log(10) copies/ml). Twenty-four percent of patients in virological failure showed wild-type viruses, likely indicating poor adherence. Even after excluding the M184V mutation, all 76% of patients in virological failure displayed viruses harboring at least one major drug resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI), non-NRTI, or protease inhibitors. Whereas the second-line regimen proposed by the 2010 WHO recommendations, including zidovudine, tenofovir, lopinavir, and atazanavir, could be effective in more than 90% of patients in virological failure with resistant viruses, the remaining patients showed genotypic profiles highly predictive of resistance to the usual WHO second-line regimen, including complex genotypic profiles diagnosed only by genotypic resistance tests in some patients. In conclusion, our observations highlight the high frequency of therapeutic failure in ARV-treated adults in this study, as well as the urgent and absolute need for improving viral load assessment in the CAR to prevent and/or, from now on, to monitor therapeutic failure.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Laboratoire de Virologie, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Péré
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Pascal
authors.initials: P
authors.lastname: Mbelesso
authors.forename: Marius
authors.initials: M
authors.lastname: Dandy
authors.forename: Mathieu
authors.initials: M
authors.lastname: Matta
authors.forename: Sandrine
authors.initials: S
authors.lastname: Moussa
authors.forename: Jean
authors.initials: J
authors.lastname: De Dieu Longo
authors.forename: Gérard
authors.initials: G
authors.lastname: Grésenguet
authors.forename: Bruno
authors.initials: B
authors.lastname: Abraham
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D002488:Central African Republic / Q000453:epidemiology; D016172:DNA Fingerprinting; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D006297:Health Services Accessibility / Q000706:statistics & numerical data; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use; D012367:RNA, Viral / Q000187:drug effects / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load / Q000187:drug effects*; D055815:Young Adult; D015215:Zidovudine / Q000627:therapeutic use; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D015215:Zidovudine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine