title: High level of HIV-1 resistance in patients failing long-term first-line antiretroviral therapy in Mali.
abstract: OBJECTIVE
  In resource-limited settings, few data are available on virological failure after long-term first-line antiretroviral therapy. This study characterized the genotypic resistance patterns at the time of failure after at least 36 months of a first-line regimen in Mali, West Africa.
  
  
  METHODS
  Plasma samples from 84 patients who were receiving first-line antiretroviral treatment and with an HIV-1 RNA viral load (VL) >1000 copies/mL were analysed. Genotypic resistance testing was performed and HIV-1 drug resistance was interpreted according to the latest version of the National Agency for HIV and Hepatitis Research algorithm.
  
  
  RESULTS
  At the time of resistance testing, patients had been treated for a median of 60 months (IQR 36-132 months) and had a median CD4 cell count of 292 cells/mm(3) (IQR 6-1319 cells/mm(3)), a median HIV-1 RNA level of 28266 copies/mL (IQR 1000-2 93 495 copies/mL) and a median genotypic susceptibility score of 1 (IQR 1-4). The prevalence of nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations was 78% and 82%, respectively. Viruses were resistant to at least one drug in 92% of cases. Although etravirine and rilpivirine were not used in the first-line regimens, viruses were resistant to etravirine in 34% of cases and to rilpivirine in 49% of cases. The treatment duration, median number of NRTI and NNRTI mutations and some reverse transcriptase mutations (T215Y/F/N, L210W, L74I, M41L and H221Y) were associated with the VL at virological failure.
  
  
  CONCLUSIONS
  This study demonstrated a high level of resistance to NRTIs and NNRTIs, compromising second-generation NNRTIs, for patients who stayed on long-term first-line regimens. It is crucial to expand the accessibility of virological testing in resource-limited settings to limit the expansion of resistance and preserve second-line treatment efficacy.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S1136, F-75005 Paris, France Inserm, UMR_S 1136, F-75005 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France djesfof@gmail.com.
authors.forename: D B
authors.initials: DB
authors.lastname: Fofana
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S1136, F-75005 Paris, France Inserm, UMR_S 1136, F-75005 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Soulié
authors.affiliation: Unité d'Epidémiologie Moléculaire de la Résistance du VIH, SEREFO-FMOS/FAPH, Université des Sciences Techniques et des Technologies, Bamako, Mali.
authors.forename: A
authors.initials: A
authors.lastname: Baldé
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S1136, F-75005 Paris, France Inserm, UMR_S 1136, F-75005 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Lambert-Niclot
authors.affiliation: Service de Pédiatrie, CHU Gabriel Toure, Université des Sciences Techniques et des Technologies, Bamako, Mali.
authors.forename: M
authors.initials: M
authors.lastname: Sylla
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S1136, F-75005 Paris, France Inserm, UMR_S 1136, F-75005 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Ait-Arkoub
authors.affiliation: CESAC, Bamako, Mali.
authors.forename: F
authors.initials: F
authors.lastname: Diallo
authors.affiliation: USAC Commune I, Bamako, Mali.
authors.forename: B
authors.initials: B
authors.lastname: Sangaré
authors.affiliation: CESAC, Bamako, Mali.
authors.forename: M
authors.initials: M
authors.lastname: Cissé
authors.affiliation: ESTHER, Bamako, Mali.
authors.forename: I A
authors.initials: IA
authors.lastname: Maïga
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S1136, F-75005 Paris, France Inserm, UMR_S 1136, F-75005 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Fourati
authors.affiliation: Unité d'Epidémiologie Moléculaire de la Résistance du VIH, SEREFO-FMOS/FAPH, Université des Sciences Techniques et des Technologies, Bamako, Mali.
authors.forename: O
authors.initials: O
authors.lastname: Koita
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S1136, F-75005 Paris, France Inserm, UMR_S 1136, F-75005 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Calvez
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S1136, F-75005 Paris, France Inserm, UMR_S 1136, F-75005 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, F-75013 Paris, France.
authors.forename: A G
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Unité d'Epidémiologie Moléculaire de la Résistance du VIH, SEREFO-FMOS/FAPH, Université des Sciences Techniques et des Technologies, Bamako, Mali Laboratoire d'Analyses Médicales, CHU Gabriel Toure, Université des Sciences Techniques et des Technologies, Bamako, Mali.
authors.forename: A I
authors.initials: AI
authors.lastname: Maïga
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008302:Mali; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: Africa; NNRTIs; failure