• Journal article

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

R. L. Goodall, D. T. Dunn, T. Pattery, A. van Cauwenberge, P. Nkurunziza, P. Awio, N. Ndembi, P. Munderi, C. Kityo, C. F. Gilks, P. Kaleebu, D. Pillay, P. Kaleebu, D. Pillay, P. Awio, M. Chirara, D. Dunn, D. M. Gibb, C. Gilks, R. Goodall, A. Kapaata, M. Katuramur, F. Lyagoba, R. Magala, B. Magambo, K. Mataruka, A.L. McCormick, L. Mugarura, T. Musunga, M. Nabankkema, J. Nkalubo, P. Nkurunziza, C. Parry, V. Robertson, M. Spyer, D. Yirrell, H. Grosskurth, P. Munderi, G. Kabuye, D. Nsibambi, R. Kasirye, E. Zalwango, M. Nakazibwe, B. Kikaire, G. Nassuna, R. Massa, K. Fadhiru, M. Namyalo, A. Zalwango, L. Generous and P. Khauka 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), pp. 1938-1944. https://doi.org/10.1093/jac/dku052

TitlePhenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda
TypeJournal article
AuthorsR. L. Goodall, D. T. Dunn, T. Pattery, A. van Cauwenberge, P. Nkurunziza, P. Awio, N. Ndembi, P. Munderi, C. Kityo, C. F. Gilks, P. Kaleebu, D. Pillay, P. Kaleebu, D. Pillay, P. Awio, M. Chirara, D. Dunn, D. M. Gibb, C. Gilks, R. Goodall, A. Kapaata, M. Katuramur, F. Lyagoba, R. Magala, B. Magambo, K. Mataruka, A.L. McCormick, L. Mugarura, T. Musunga, M. Nabankkema, J. Nkalubo, P. Nkurunziza, C. Parry, V. Robertson, M. Spyer, D. Yirrell, H. Grosskurth, P. Munderi, G. Kabuye, D. Nsibambi, R. Kasirye, E. Zalwango, M. Nakazibwe, B. Kikaire, G. Nassuna, R. Massa, K. Fadhiru, M. Namyalo, A. Zalwango, L. Generous and P. Khauka
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/mm3) 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 IC50 (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.

JournalJournal of Antimicrobial Chemotherapy
Journal citation69 (7), pp. 1938-1944
ISSN0305-7453
1460-2091
Year2014
PublisherOxford University Press
Publisher's version
License
CC BY 3.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1093/jac/dku052
Web address (URL)http://dx.doi.org/10.1093/jac/dku052
Publication dates
Published01 Jul 2014

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