HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa


Kityo, C; Thompson, J; Nankya, I; Hoppe, A; Ndashimye, E; Warambwa, C; Mambule, I; van Oosterhout, JJ; Wools-Kaloustian, K; Bertagnolio, S; Easterbrook, PJ; Mugyenyi, P; Walker, AS; Paton, NI; Europe Africa Research Network For Evaluation Of Second-Line The, T; (2017) HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. Journal of acquired immune deficiency syndromes (1999), 75 (2). e45-e54. ISSN 1525-4135 DOI: https://doi.org/10.1097/QAI.0000000000001285

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Abstract

OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs. DESIGN: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, and Malawi were analyzed. Multivariable logistic regression was used to determine the association between specific DRMs and Stanford intermediate-/high-level resistance and factors including REGA subtype, first-line antiretroviral therapy drugs, CD4, and VL at failure. RESULTS: The median first-line treatment duration was 4 years (interquartile range 30-43 months); 42% of participants had VL >/=100,000 copies/mL and 63% participants had CD4 <100 cells/mm. Viral subtype distribution was A1 (40%; Uganda and Kenya), C (31%; Zimbabwe and Malawi), and D (25%; Uganda and Kenya), and recombinant/unclassified (5%). In general, DRMs were more common in subtype-C than in subtype-A and/or subtype-D (nucleoside reverse transcriptase inhibitor mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, and H221Y). The presence of tenofovir resistance was similar between subtypes [P (adjusted) = 0.32], but resistance to zidovudine, abacavir, etravirine, or rilpivirine was more common in subtype-C than in subtype-D/subtype-A [P (adjusted) < 0.02]. CONCLUSIONS: Non-B subtypes differ in DRMs at first-line failure, which impacts on residual nucleoside reverse transcriptase inhibitor and NNRTI susceptibility. In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens.

Item Type: Article
Keywords: Adult, Africa South of the Sahara/epidemiology, Anti-HIV Agents/*therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, Viral/*drug effects/*genetics, Female, HIV Infections/*drug therapy/immunology/*virology, HIV Reverse Transcriptase/genetics, HIV-1/*classification/drug effects/*genetics/physiology, Humans, Male, Middle Aged, Mutation/drug effects, Reverse Transcriptase Inhibitors/*therapeutic use, Treatment Failure, Viral Load/drug effects, Adult, Africa South of the Sahara, epidemiology, Anti-HIV Agents, therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, Viral, drug effects, genetics, Female, HIV Infections, drug therapy, immunology, virology, HIV Reverse Transcriptase, genetics, HIV-1, classification, drug effects, genetics, physiology, Humans, Male, Middle Aged, Mutation, drug effects, Reverse Transcriptase Inhibitors, therapeutic use, Treatment Failure, Viral Load, drug effects
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 28129253
URI: http://researchonline.lshtm.ac.uk/id/eprint/4646731

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