Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study

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

doi:10.1016/S1473-3099(16)30469-8

- Add this to...
- Twitter
- Facebook
- Google Bookmarks
- LinkedIn

Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study

Published Date:

Dec 01 2016

Publisher's site:

http://dx.doi.org/10.1016/S1473-3099(16)30469-8 New Site Icon

Source:

Lancet Infect Dis. 17(3):296-304

Language:

English

[PDF-767.14 KB]

Details:

Personal Authors:

Gregson, John ; Kaleebu, Pontiano ; Marconi, Vincent C ; van Vuuren, Cloete ; ChB, MB ; ... More ▼

Keywords:

[+]

Pubmed ID:

27914856

Pubmed Central ID:

PMC5421555

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.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

Place as Subject:

Africa South of the Sahara

Main Document Checksum:

[+]

Supporting Files:

	nihms855948f4.gif	image/gif
	nihms855948f4.jpg	image/jpeg
	NIHMS855948-supplement-Supplementary_data.pdf	application/pdf
	nihms855948.nxml	text/xml
	nihms855948f1.gif	image/gif
	nihms855948f1.jpg	image/jpeg
	nihms855948f2.gif	image/gif
	nihms855948f2.jpg	image/jpeg
	nihms855948f3.gif	image/gif
	nihms855948f3.jpg	image/jpeg

No Related Documents.

You May Also Like:

Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

Personal Author:

Rhee, Soo-Yon; Varghese, Vici; Holmes, Susan P.; Van Zyl, Gert U.; Steegen, Kim; Boyd, Mark A.; Cooper, David A.; Nsanzimana, Sabin; Saravanan, Shanmugam; Charpentier, Charlotte; de Oliveira, Tulio; Etiebet, Mary-Ann A.; Garcia, Federico; Goedhals, Dominique; Gomes, Perpetua; Günthard, Huldrych F.; Hamers, Raph L.; Hoffmann, Christopher J; Hunt, Gillian; Jiamsakul, Awachana; Kaleebu, Pontiano; Kanki, Phyllis; Kantor, Rami; Kerschberger, Bernhard; Marconi, Vincent C.; D'amour Ndahimana, Jean; Ndembi, Nicaise; Ngo-Giang-Huong, Nicole; Rokx, Casper; Santoro, Maria M.; Schapiro, Jonathan M.; Schmidt, Daniel; Seu, Lillian; Sigaloff, Kim C.E.; Sirivichayakul, Sunee; Skhosana, Lindiwe; Sunpath, Henry; Tang, Michele; Yang, Chunfu; Carmona, Sergio; Gupta, Ravindra K.; Shafer, Robert W.;

Published:

Mar 19 2017

Source:

EBioMedicine. 2017; 18:225-235.

Description:

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse...

File Type:

[PDF - 727.61 KB]
Expansion of Viral Load Testing and the Potential Impact on Human Immunodeficiency Virus Drug Resistance

Personal Author:

Chun, Helen M.; Obeng-Aduasare, Yaa F.; Broyles, Laura N.; Ellenberger, Dennis;

Published:

Dec 01 2017

Source:

J Infect Dis. 216(Suppl 9):S808-S811

Description:

Increasing the volume, strengthening the quality, and proactively using data of human immunodeficiency virus (HIV) load testing are pivotal to limiting the threat of HIV drug resistance (HIVDR) accumulation,and allow for optimal case-based HIVDR surv...

File Type:

[PDF - 48.26 KB]
Viral Suppression Following Switch to Second-line Antiretroviral Therapy: Associations With Nucleoside Reverse Transcriptase Inhibitor Resistance and Subtherapeutic Drug Concentrations Prior to Switch

Personal Author:

Johnston, Victoria; Cohen, Karen; Wiesner, Lubbe; Morris, Lynn; Ledwaba, Johanna; Fielding, Katherine L.; Charalambous, Salome; Churchyard, Gavin; Phillips, Andrew; Grant, Alison D.;

Published:

Aug 13 2013

Source:

J Infect Dis. 2013; 209(5):711-720.

Series:

PEPFAR

Description:

High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification.|Using prospectively collected data from patients in South Africa, ...

File Type:

[PDF - 301.77 KB]
Characterization of HIV Drug Resistance Mutations Among Patients Failing First-Line Antiretroviral Therapy From a Tertiary Referral Center in Lusaka, Zambia

Personal Author:

Seu, Lillian; Mulenga, Lloyd B.; Siwingwa, Mpanji; Sikazwe, Izukanji; Lambwe, Nason; Guffey, M. Bradford; Chi, Benjamin H.;

Published:

Mar 05 2015

Source:

J Med Virol. 2015; 87(7):1149-1157

Description:

In settings of resource constraint, an understanding of HIV drug resistance can guide antiretroviral therapy (ART) at switch to second-line therapy. To determine the prevalence of such HIV drug resistance mutations (HIV DRM), we used an in-house sequ...

File Type:

[PDF - 254.70 KB]
Measuring Enzymatic HIV-1 Susceptibility to Two Reverse Transcriptase Inhibitors as a Rapid and Simple Approach to HIV-1 Drug-Resistance Testing

Personal Author:

Hoffmann, Dieter.; Garcia, Albert D.; Harrigan, P. Richard.; Johnston, Ian C. D.; Nakasone, Tadashi.; García-Lerma, J. Gerardo.; Heneine, Walid.;

Published:

Jul 20 2011

Source:

PLoS One. 2011; 6(7).

Description:

Simple and cost-effective approaches for HIV drug-resistance testing are highly desirable for managing increasingly expanding HIV-1 infected populations who initiate antiretroviral therapy (ART), particularly in resource-limited settings. Non-nucleos...

File Type:

[PDF - 177.82 KB]