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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; ... Paton, N; + view all (2017) HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa. JAIDS: Journal of Acquired Immune Deficiency Syndromes , 75 (2) e45-e54. 10.1097/QAI.0000000000001285. Green open access

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Abstract

OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) regimens in programmes without routine viral load (VL) monitoring and to examine inter-subtype differences in DRMs. DESIGN: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, Malawi were analysed. 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 ART drugs, CD4 and VL at failure. RESULTS: The median first-line treatment duration was 4 years (IQR 30-43 months); 42% of participants had VL >=100,000 c/ml and 63% had CD4<100cells/mm3. Viral subtype distribution was A1 (40%; Uganda, Kenya), C (31%; Zimbabwe, Malawi) and D (25%; Uganda, Kenya) and recombinant/unclassified (5%). In general, DRMs were more common in subtype-C than in subtypes-A and/or -D (NRTI mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, 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 D/A (p(adjusted)<0.02). CONCLUSIONS: Non-B subtypes differ in DRMs at first-line failure that impact on residual NRTI and NNRTI susceptibility. In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens.

Type: Article
Title: HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAI.0000000000001285
Publisher version: http://dx.doi.org/10.1097/QAI.0000000000001285
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/1531989
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