High level of HIV-1 resistance in patients failing long-term first-line antiretroviral therapy in Mali

• Published in: Journal of antimicrobial chemotherapy Vol. 69; no. 9; pp. 2531 - 2535
• Main Authors: Fofana, D B, Soulié, C, Baldé, A, Lambert-Niclot, S, Sylla, M, Ait-Arkoub, Z, Diallo, F, Sangaré, B, Cissé, M, Maïga, I A, Fourati, S, Koita, O, Calvez, V, Marcelin, A G, Maïga, A I
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.09.2014
• Subjects: Adolescent; Adult; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Drug resistance; Drug Resistance, Viral; Female; Genotype; Genotyping Techniques; HIV; HIV Infections - drug therapy; HIV Infections - virology; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus; Humans; Male; Mali; Median; Microbial Sensitivity Tests; Middle Aged; Mutation, Missense; Patients; RNA, Viral - genetics; Treatment Failure; Young Adult; Mali; failure; Africa; NNRTIs
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dku153

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. 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. 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. 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.