HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Crosssectional Design

Title:HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Crosssectional Design

Volume: 15 Issue: 1

Author(s): Aubin J. Nanfack, Desire Takou, Joseph Fokam, Romina Salpini, Maria M. Santoro, Giulia Cappelli, Martin Baane, Suzie M. Tetang, Josef Eberle, Lutz Gurtler, Francesca Ceccherini-Silberstein, Judith N. Torimiro, Vittorio Colizzi, Carlo-Federico Perno and Alexis Ndjolo

Affiliation:

Keywords: Treatment regimens, HIV drug resistance, protease-reverse transcriptase, integrase, V3 loop, Cameroon.

Abstract: Background: Scale-up of antiretroviral therapy (ART) and the growing number of longterm 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 secondline 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.

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.

Cite this article as:

Nanfack J. Aubin, Takou Desire, Fokam Joseph, Salpini Romina, Santoro M. Maria, Cappelli Giulia, Baane Martin, Tetang M. Suzie, Eberle Josef, Gurtler Lutz, Ceccherini-Silberstein Francesca, Torimiro N. Judith, Colizzi Vittorio, Perno Carlo-Federico and Ndjolo Alexis, HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Crosssectional Design, Current HIV Research 2017; 15 (1) . https://dx.doi.org/10.2174/1570162X14666161230105417

DOI https://dx.doi.org/10.2174/1570162X14666161230105417	Print ISSN 1570-162X
Publisher Name Bentham Science Publisher	Online ISSN 1873-4251