HIV-1 drug susceptibility to potential second- and third-line antiretroviral regimens among cameroonian patients: Evidence from a crosssectional design
2017
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-naive, 24 failing first-line, 24 failing secondline
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.
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