Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

Goodall, R. L., Dunn, D. T., Pattery, T., van Cauwenberge, A., Nkurunziza, P., Awio, P., Ndembi, N., Munderi, P., Kityo, C., Gilks, C. F., Kaleebu, P. and Pillay, D. (2014) Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. Journal of Antimicrobial Chemotherapy, 69 7: 1938-1944. doi:10.1093/jac/dku052


Author Goodall, R. L.
Dunn, D. T.
Pattery, T.
van Cauwenberge, A.
Nkurunziza, P.
Awio, P.
Ndembi, N.
Munderi, P.
Kityo, C.
Gilks, C. F.
Kaleebu, P.
Pillay, D.
Title Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 0305-7453
1460-2091
Publication date 2014
Year available 2014
Sub-type Article (original research)
DOI 10.1093/jac/dku052
Open Access Status
Volume 69
Issue 7
Start page 1938
End page 1944
Total pages 7
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2015
Language eng
Abstract Objectives: We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring. Methods: NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm. 3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC. 50 (FC) relative to wild-type virus. Results: HIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm. Conclusions: Our data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility.
Keyword Africa
Hypersusceptibility
Resistance
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Public Health Publications
 
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Created: Wed, 21 Jan 2015, 11:24:33 EST by Nyree Divitini on behalf of School of Public Health