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. 2012;17(2):313-20.
doi: 10.3851/IMP1985. Epub 2011 Nov 18.

Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy

Carole L Wallis  1 , Maria A Papathanasopolous, Matthew Fox, Francesca Conradie, Prudence Ive, Catherine Orrell, Jennifer Zeinecker, Ian Sanne, Robin Wood, James McIntyre, Wendy Stevens; CIPRA-SA project 1 study team
Collaborators, Affiliations

Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy

Carole L Wallis et al. Antivir Ther. 2012.

Abstract

Background: The emergence of complex HIV-1 drug resistance mutations has been linked to the duration of time patients are on a failing antiretroviral drug regimen. This study reports on resistance profiles in a closely monitored subtype C infected cohort.

Methods: A total of 812 participants were enrolled into the CIPRA-SA 'safeguard the household' study, viral loads were determined at 12-weekly intervals for 96 weeks. Virological failure was defined as either a <1.5 log decrease in viral load at week 12 or two consecutive viral load measurements of >1,000 RNA copies/ml after week 24. Regimens prescribed were in line with the South African roll-out programme (stavudine, lamivudine, efavirenz or nevirapine). Viral RNA was extracted from patients with virological failure, and pol reverse-transcriptase PCR and sequence analysis were performed to determine drug-resistant mutations.

Results: Virological failure was observed in 83 participants on the first-line regimen during the study period, of which 61 (73%) had HIV-1 drug-resistant mutations. The M184V mutation was the most frequent (n=46; 65%), followed by K103N (46%) and Y181C (21%). Thymidine analogue mutations were infrequent (1%) and Q151M was not observed.

Conclusions: Drug resistance profiles were less complex than has been previously reported in South Africa using the same antiretroviral drug regimens. These data suggest that frequent viral load monitoring limits the level and complexity of resistance observed in HIV-1 subtype C, preserving susceptibility to second-line options.

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Conflict of interest statement

Potential conflicts of interest: No conflict of interest for any authors

Figures

Figure 1
Figure 1. Frequency of the HIV-1 antiretroviral drug resistance mutations associated with NRTIsa resistance in the 83CIPRA-SAb participants experiencing viral failure onARV therapy in South Africa
aNRTI = nucleoside reverse transcriptase inhibitor bCIPRA-SA is the Comprehensive International Program of Research on AIDS-South Africa.
Figure 2
Figure 2. HIV-1 antiretroviral resistance patterns in 70 participants experiencing viral rebound on first-line therapy in the CIPRA-SAb study in South Africa
a Participants on a PIs-based regimen are represented by black asterisks, if they were also exposed to sdNVP to prevent mother-to-child-transmission the asterisks is red. b CIPRA-SA is the Comprehensive International Program of Research on AIDS-South Africa.
Figure 3
Figure 3. Distribution of NNRTIsa mutations in patients failing Efavirenz (n=49)or Nevirapine(n=22) -containing first-line antiretroviral regimens in the CIPRA-SAb study in South Africa
The error bars represent the confidence intervals. a NNRTI = non-nucleoside reverse transcriptase inhibitor. b CIPRA-SA is the Comprehensive International Program of Research on AIDS-South Africa.
See this image and copyright information in PMC

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