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High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa

High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa
High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa
Objective

To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.

Design

Cross-sectional study nested within HIV treatment programme.

Methods

Adult (?18 years) HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART) regimen and with evidence of virological failure (one viral load >1000 copies/ml) were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.

Results

A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%); and stavudine, lamivudine and nevirapine (24%). Median duration of ART was 42 months (interquartile range (IQR) 32–53) and median duration of antiretroviral failure was 27 months (IQR 17–40). One hundred and ninety one (86%) had at least one drug resistance mutation. For 34 individuals (15%), the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI) substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR) 5.70, 95% confidence interval (CI) 2.60–12.49).

Conclusions

There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.
1932-6203
1-10
Manasa, J.
a186cb2c-8692-44a0-b67e-1937bda43b2a
Lessells, R.J.
54b2808f-a135-46ea-92df-ad2e6512dbf8
Skingsley, A.
449bc0b4-dbc2-41fb-afbd-773c055670d2
Naidu, K.K.
d178b37c-f8fe-486f-917a-97f2f73dd82b
Newell, M.L.
c6ff99dd-c23b-4fef-a846-a221fe2522b3
De Oliveira, T.
c657f813-01c5-4700-bc81-f34b163b8003
McGrath, N.
b75c0232-24ec-443f-93a9-69e9e12dc961
Manasa, J.
a186cb2c-8692-44a0-b67e-1937bda43b2a
Lessells, R.J.
54b2808f-a135-46ea-92df-ad2e6512dbf8
Skingsley, A.
449bc0b4-dbc2-41fb-afbd-773c055670d2
Naidu, K.K.
d178b37c-f8fe-486f-917a-97f2f73dd82b
Newell, M.L.
c6ff99dd-c23b-4fef-a846-a221fe2522b3
De Oliveira, T.
c657f813-01c5-4700-bc81-f34b163b8003
McGrath, N.
b75c0232-24ec-443f-93a9-69e9e12dc961

Manasa, J., Lessells, R.J., Skingsley, A., Naidu, K.K., Newell, M.L., De Oliveira, T. and McGrath, N. (2013) High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa. PLoS ONE, 8 (8), 1-10. (doi:10.1371/journal.pone.0072152). (PMID:23991055)

Record type: Article

Abstract

Objective

To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.

Design

Cross-sectional study nested within HIV treatment programme.

Methods

Adult (?18 years) HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART) regimen and with evidence of virological failure (one viral load >1000 copies/ml) were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.

Results

A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%); and stavudine, lamivudine and nevirapine (24%). Median duration of ART was 42 months (interquartile range (IQR) 32–53) and median duration of antiretroviral failure was 27 months (IQR 17–40). One hundred and ninety one (86%) had at least one drug resistance mutation. For 34 individuals (15%), the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI) substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR) 5.70, 95% confidence interval (CI) 2.60–12.49).

Conclusions

There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.

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More information

Published date: 21 August 2013
Organisations: Primary Care & Population Sciences

Identifiers

Local EPrints ID: 362912
URI: https://eprints.soton.ac.uk/id/eprint/362912
ISSN: 1932-6203
PURE UUID: 62100162-3c29-4784-9dfe-18e7521c419f
ORCID for M.L. Newell: ORCID iD orcid.org/0000-0002-1074-7699
ORCID for N. McGrath: ORCID iD orcid.org/0000-0002-1039-0159

Catalogue record

Date deposited: 10 Mar 2014 16:42
Last modified: 20 Jul 2019 00:39

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