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Nanfack, Aubin J.; Takou, Desire; Fokam, Joseph; Salpini, Romina; Santoro, Maria M.; Cappelli, Giulia; Baane, Martin; Tetang, Suzie M.; Eberle, Josef; Gurtler, Lutz; Ceccherini-Silberstein, Francesca; Torimiro, Judith N.; Colizzi, Vittorio; Perno, Carlo-Federico; Ndjolo, Alexis (2017): HIV-1 Drug Susceptibility to Potential Second-and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Cross-sectional Design. In: Current Hiv Research, Vol. 15, No. 1: pp. 66-73
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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-naive, 24 failing first-line, 24 failing second-line ART) living in Yaounde-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 naive, first- to second-line, had respectively 5.30, 4.85 and 4.66 log HIV RNA, and 532, 203 and 146 CD4 cells/mm(3)), and infected with diverse HIV-1 non-B clades (58.1% CRF02_AG). Among ART-naive 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. Conclusion: 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.