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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-saharan african countries: Implications for second-line ART strategies
Clinical Infectious Diseases, Volume 54, No. 11, Year 2012
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Description
Background.Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African countries and predicted their impact on second-line drug susceptibility.Methods.A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility.Results.HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine.Conclusions.Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority. © 2012 The Author.
Authors & Co-Authors
Hamers, Raph L.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Netherlands, Amsterdam
Universiteit Van Amsterdam
Netherlands, Amsterdam
Amsterdam Institute for Global Health and Development
Sigaloff, Kim Catherina Eve
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Netherlands, Amsterdam
Universiteit Van Amsterdam
Netherlands, Amsterdam
Amsterdam Institute for Global Health and Development
Wensing, Annemarie Marie J.
Netherlands, Utrecht
University Medical Center Utrecht
Wallis, Carole Lorraine
South Africa, Johannesburg
University of the Witwatersrand
Kityo, Cissy Mutuluuza
Uganda, Kampala
Joint Clinical Research Center Uganda
Siwale, Margaret
Zambia, Lusaka
Lusaka Trust Hospital
Mandaliya, Kishor N.
Kenya, Mombasa
Coast Provincial General Hospital, Kenya
Ive, Prudence D.
South Africa, Johannesburg
University of the Witwatersrand
Botes, Mariëtte E.
South Africa, Pretoria
Muelmed Hospital
Wellington, Maureen
Zimbabwe, Harare
Newlands Clinic
Osibogun, Akin A.
Nigeria, Lagos
Lagos University Teaching Hospital
Stevens, Wendy Susan
South Africa, Johannesburg
University of the Witwatersrand
Rinke de Wit, Tobias Floris
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Netherlands, Amsterdam
Universiteit Van Amsterdam
Netherlands, Amsterdam
Amsterdam Institute for Global Health and Development
Schuurman, Rob J.
Netherlands, Utrecht
University Medical Center Utrecht
Statistics
Citations: 175
Authors: 14
Affiliations: 11
Identifiers
Doi:
10.1093/cid/cis254
ISSN:
10584838
e-ISSN:
15376591
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Quantitative