Details:

Alternative Title:
Lancet Infect Dis
Publisher's site:
http://dx.doi.org/10.1016/S1473-3099(16)30469-8
Personal Author:
Gregson, John ; Kaleebu, Pontiano ; Marconi, Vincent C ; van Vuuren, Cloete ; ChB, MB ; ... More +
Gregson, John ; Kaleebu, Pontiano ; Marconi, Vincent C ; van Vuuren, Cloete ; ChB, MB ; Ndembi, Nicaise ; Hamers, Raph L ; Kanki, Phyllis ; Hoffmann, Christopher J ; Lockman, Shahin ; Pillay, Deenan ; de Oliveira, Tulio ; Clumeck, Nathan ; Hunt, Gillian ; Kerschberger, Bernhard ; Shafer, Robert W ; Yang, Chunfu ; Raizes, Elliot ; Kantor, Rami ; Gupta, Ravindra K Less -
Description:
Background

HIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART.

Methods

We retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs.

Findings

Of 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60·5 cells per μL [IQR 21·0–128·0] in patients with TAMS vs 95·0 cells per μL [37·0–177·0] in patients without TAMs; p=0·007) and were more likely to have tenofovir resistance (93 [81%] of 115 patients with TAMs vs 352 [59%] of 597 patients without TAMs; p<0·0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0·0001), and cytosine analogue resistance (100 [87%] vs 378 [63%]; p=0·0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0·64 (p<0·0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1·29 (1·13–1·47; p<0·0001)

Interpretation

TAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains.


Subjects:
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Adult Antiretroviral Therapy, Highly Active Article Benzoxazines Drug Resistance, Viral Female HIV-1 HIV Infections Humans Lamivudine Male Mutation Nevirapine Retrospective Studies Reverse Transcriptase Inhibitors Tenofovir Treatment Failure Viral Load
Source:
Lancet Infect Dis. 17(3):296-304
Pubmed ID:
27914856
Pubmed Central ID:
PMC5421555
Document Type:
Journal Article
Funding:
P30 AI050409/AI/NIAID NIH HHS/United States ; R01 AI066922/AI/NIAID NIH HHS/United States ; UM1 AI069456/AI/NIAID NIH HHS/United States ; R01 AI108441/AI/NIAID NIH HHS/United States ; U2G GH000925/GH/CGH CDC HHS/United States ; ... More +
P30 AI050409/AI/NIAID NIH HHS/United States ; R01 AI066922/AI/NIAID NIH HHS/United States ; UM1 AI069456/AI/NIAID NIH HHS/United States ; R01 AI108441/AI/NIAID NIH HHS/United States ; U2G GH000925/GH/CGH CDC HHS/United States ; G0600044/Medical Research Council/United Kingdom ; R01 AI068581/AI/NIAID NIH HHS/United States ; MC_U950080938/Medical Research Council/United Kingdom ; UL1 TR000454/TR/NCATS NIH HHS/United States ; Wellcome Trust/United Kingdom ; P30 AI042853/AI/NIAID NIH HHS/United States ; UL1 RR025008/RR/NCRR NIH HHS/United States ; R01 AI098558/AI/NIAID NIH HHS/United States Less -
Place as Subject:
Africa South of the Sahara
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:131cd6bd6a4db8a9f572b0157cd32d78e6995910a8f4c0fbe895d98c70417a2c
Download URL:
https://stacks.cdc.gov/view/cdc/45675/cdc_45675_DS1.pdf
File Type:

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