High levels of drug resistance after failure of first-line antiretroviral therapy in rural South Africa: impact on standardised second-line regimens

Manasa, J., McGrath, N., Lessells, R., Skingsley, A., Newell, M.L. and de Oliveira, T. (2012) High levels of drug resistance after failure of first-line antiretroviral therapy in rural South Africa: impact on standardised second-line regimens. XIX International AIDS Conference (AIDS 2012), Washington, United States. 22 - 27 Jul 2012.

Abstract

Background: Rapid scale-up of antiretroviral therapy (ART) in Southern Africa has put enormous strain on health systems. Information about acquired drug resistance in treated individuals is important to monitor quality of programmes and to ensure that ART policies remain appropriate. The majority of resistance data so far have come from urban, hospital-based programmes; limited data have been reported from rural treatment programmes.

Methods: Adult (?16 years) HIV-infected individuals with virological failure (2 x VL>1000 copies/ml) on first-line NNRTI-based ART were enrolled from all 17 primary health care clinics of the Hlabisa ART Programme. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) were calculated using RegaDB and Stanford HIVDB 6.0.5 algorithms.

Results: 187 adults enrolled between Dec 2010 and Dec 2011; median age 37 years (IQR 31-45); 70% female. Median time on ART 41 months (IQR 31-53); median time on failing regimen 30 months (IQR 20-42). 120 (64%) had never achieved full virological suppression (VL?50 copies/ml). 160 (86%) individuals had ?1 drug resistance mutation; 149 (80%) and 153 (82%) respectively had NRTI and NNRTI mutations. 72 (38%) had at least one thymidine analogue mutation (TAM) and 32 (17%) had ?3 TAMs. 14 (7%) had other NRTI mutations that might impact on second-line therapy (K65R - 12 (6%); Q151M - 3 (2%)). The standard second-line regimen was substantially compromised (defined as GSS ?1.5) in 33 (18%) individuals.

Conclusions: There are high levels of acquired drug resistance associated with prolonged virological failure in this rural primary health care programme. Standard second-line regimens would be significantly compromised in almost one in five adults. This suggests a role for genotypic resistance testing in routine care but, more importantly, it highlights the need for increased attention to quality of care and adherence to virological monitoring guidelines.

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Contributors

Author: N. McGrath

Author: M.L. Newell

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