HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme

Abstract

Background: This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa.

Methods: This was an observational cohort. Genotypic resistance testing was performed on treatment-naive individuals and those failing first-line ART (confirmed HIV-1 RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002-2007). Resistance profiles and mutations relative to timing of known virological failure were examined.

Results: In total, 230 patients (120 treatment-naive and 110 with virological failure) were included: 98% had clade C virus. Among treatment-naive patients, prevalence of primary resistance was 2.5% (95% confidence interval 0.0-5.3). Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A. Among treatment-experienced patients, 95 (86%) individuals had therapy-limiting NNRTI mutations, including K103N (55%), V106M (31%) and Y181C (9%). The M184V mutation was the most common mutation, found in 86 (78%) patients. In total, 10 (9%) patients had the K65R mutation. More individuals tended to develop thymidine analogue mutations when sampling occurred after 6 months of detected therapy failure (10/31 [32%] individuals) compared with those who had genotyping before 6 months (15/79 [19%] patients; P=0.246).

Conclusions: Prevalence of primary resistance in a sample of ART-naive clade C HIV-1-infected individuals in South Africa was low during the study period. Patients failing first-line ART most often developed resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, the two drug classes used in first-line therapy. Viral load monitoring in this setting is crucial and individual genotypes in those failing first-line therapy should be considered.

Figure 1

This illustrates the proportion of individuals with either M184V (figure 1a), TAMs (figure 1b) or NNRTI mutations (figure 1c) by time between initial virological breakthrough (first viral load >1000 copies/ml) and failure (at the time of the second consecutive viral load >1000 copies/ml). Individuals were divided into those whose genotype (taken at the time of failure) was completed on or before 180 days (n=79) from breakthrough or after 180 days (n=31). None of the differences were significant, though a trend to more TAMS with more time on failing therapy was noted.

Figure 2

Association between non-TAM resistance and development of TAMs in the reverse transcriptase gene.