title: HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Cross-sectional Design.
abstract: BACKGROUND
  Scale-up of antiretroviral therapy (ART) and the growing number of long-term treated patients may favor multi-HIV drug resistance (HIVDR) in resource-limited settings. Understanding the burden of HIVDR with ART-exposure may provide new insights for an effective long-term management of infected patients.
  
  
  METHODS
  Sixty-six HIV-infected individuals (18 ART-naïve, 24 failing first-line, 24 failing second-line ART) living in Yaoundé-Cameroon were evaluated by sequencing protease-reverse transcriptase (PR-RT, n=62), envelope-V3 loop (V3, n=58) and integrase (IN, n=30) regions. Drug resistance mutations (DRMs) were interpreted using Stanford University HIV drug resistance database and geno2pheno, while viral tropism prediction was done using geno2pheno, position-specific scoring matrices (PSSM) and Net charge rule.
  
  
  RESULTS
  Participants, from naïve, first- to second-line, had respectively 5.30, 4.85 and 4.66 log HIV RNA, and 532, 203 and 146 CD4 cells/mm3), and infected with diverse HIV-1 non-B clades (58.1% CRF02_AG). Among ART-naïve patients, 6.7% harbored K103N, 28.6% had IN accessory-mutations (L74I, E157Q) and 26.7% carried CXCR4-tropic viruses. At first-line failure, 79.2% harbored DRMs to nucleoside and non-nucleoside RT inhibitors, 33.3% had IN accessory-mutations (L68I, L74I, T97A, E157Q), and 47.4% carried CXCR4-tropic viruses. At second-line failure, 91.3% harbored multi-DRMs to PR-RT inhibitors (with 52.2% and 4.3% DRMs to second-generation NNRTIs and darunavir/r, respectively), 27.3% had IN accessory-mutations (L74I, T97A, E157EQ), and 37.5% carried CXCR4-tropic viruses.
  
  
  CONCLUSIONS
  Levels of PR-RT resistance increases with ART-exposure, with needs for new ART-options following second-line failure. IN inhibitors and darunavir/r are potentially suitable for a third-line regimen, while the use of maraviroc, etravirine or rilpivirine, requires individual genotypic testing.
authors.forename: Aubin J
authors.initials: AJ
authors.lastname: Nanfack
authors.forename: Desire
authors.initials: D
authors.lastname: Takou
authors.affiliation: Sequencing and Bioinformatics Unit, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé-Cameroon.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fokam
authors.forename: Romina
authors.initials: R
authors.lastname: Salpini
authors.forename: Maria M
authors.initials: MM
authors.lastname: Santoro
authors.forename: Giulia
authors.initials: G
authors.lastname: Cappelli
authors.forename: Martin
authors.initials: M
authors.lastname: Baane
authors.forename: Suzie M
authors.initials: SM
authors.lastname: Tetang
authors.forename: Josef
authors.initials: J
authors.lastname: Eberle
authors.forename: Lutz
authors.initials: L
authors.lastname: Gürtler
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Judith N
authors.initials: JN
authors.lastname: Torimiro
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colizzi
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Alexis
authors.initials: A
authors.lastname: Ndjolo