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1.  HIV-1 clade C resistance genotypes in naïve patients and after first virological failure in a large community ART programme 
Antiviral therapy  2009;14(4):523-531.
To evaluate HIV drug resistance pre-treatment, and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART), in South Africa.
An observational cohort.
Genotypic resistance testing was performed on naïve individuals and those failing first-line ART (confirmed HIV RNA >1000 copies/ml) from public sector clinics in the Cape Town (2002 – 2007). Resistance profiles and mutations relative to timing of known virological failure were examined.
230 patients (120 naïve; 110 with virologic failure) were included; 98% had clade C virus. Among naïve patients, prevalence of primary resistance was 2.5% (95% CI:0.0%-5.3%). Three patients had 1 significant reverse transcriptase (RT) mutation: K65R, Y181C and G190A. Among non-naïve patients, 95 individuals (86%) had therapy-limiting NNRTI mutations including K103N (55%), V106M (31%) and Y181C (9%). The M184V mutation was the most common mutation seen in 86 patients (78%). Ten patients (9%) had the K65R mutation. More individuals tended to develop thymidine analogue mutations (TAMs) when sampling occurred after 6 months of detected therapy failure [10/31 individuals (32%)], compared to those who had genotyping before 6 months [15/79 patients (19%)] (p=0.246).
Prevalence of primary resistance in a sample of ART-naïve clade C HIV-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 critical and individual genotypes in those failing first-line therapy should be considered.
PMCID: PMC3211093  PMID: 19578237
antiretroviral therapy; Africa; clade C; resistance; genotype
2.  HIV testing rates and outcomes in a South African community, 2001–2006: implications for expanded screening policies 
Revised World Health Organization recommendations seek to increase HIV testing. We assessed the need for expanded testing in South Africa by examining current testing and treatment trends among a high-prevalence population.
We determined the numbers of adults receiving HIV testing and antiretroviral treatment (ART) during 2001–2006 using testing registers linked to patient records from two healthcare facilities believed responsible for virtually all HIV services available to the population. We evaluated annual population testing rates using census population counts; proportions of clients testing seropositive (yield); CD4 counts and WHO stage at diagnosis; and ART initiation rates.
HIV testing rates rose from 4% in 2001 to 20% in 2006 (p<0.001) and were highest among pregnant females receiving provider-initiated testing. Yield for first-time testers decreased from 47% in 2001 to 28% in 2006. Median CD4 counts and WHO stage distributions for newly-diagnosed clients remained stable. HIV-infected clients receiving ART within six months of eligibility increased from 0% in 2001 to 68% in 2006 (p<0.001).
Population testing and ART initiation rates rose dramatically during 2001–2006. Yet, yield remained high and HIV-infected persons continued to receive late diagnoses. These findings highlight the continuing need for expanded testing and linkage to care.
PMCID: PMC3209660  PMID: 19582895
3.  Quality of life and the impact of drug toxicities in a South African community-based antiretroviral programme 
The impact of highly active antiretroviral therapy (HAART) on health-related quality of life has been widely researched in the developed world, but there are few data from sub-Saharan Africa, where the vast majority of HIV-infected individuals live. This study examined health-related quality of life among HIV-positive individuals initiating HAART in Cape Town, South Africa, and explored the impact of HAART-related drug toxicities on quality of life.
Health-related quality of life was assessed using a standardised questionnaire, the Medical Outcomes Survey Short Form 36. Physical health summary scores and mental health summary scores were compared pre-HAART and at regular intervals during the first 48 weeks of HAART. The relationships between socio-demographic, baseline and on-treatment variables and decline in health-related quality of life, as well as the impact of drug toxicities on quality of life, were assessed in unadjusted bivariate and adjusted multivariate analyses.
Two hundred and ninety-five patients were enrolled into the study. There was a significant increase in health-related quality of life during the first 48 weeks on HAART. The median physical health summary score increased from 45 to 53 units (p < 0.001) and median mental health summary score increased from 45 to 50 units (p < 0.001).
The bulk of this increase occurred during the first 16 weeks. Overall, 23% of participants experienced a decline in their physical health summary score, while 34% showed a decline in the mental health summary score. Average drops in median physical and mental health summary scores were 8.4 units (SD 9.31) and 9.9 (SD 11.4) units respectively. Participants with drug toxicity had lower physical health summary scores than participants without drug toxicity at all time points. However, only three participants with toxicity (27%) reported an actual decline in health-related quality of life by week 48. Drug toxicities had little impact on mental health summary scores.
These results confirm the health-related quality of life benefits of HAART. While the majority of patients experienced a significant improvement in health-related quality of life on HAART, up to a third of patients reported declines in this quality of life. This was largely related to better baseline clinical state. HAART-related drug toxicities did not have a significant impact on health-related quality of life during the first year of HAART, which supports the ongoing use of the current national first-line regimen.
PMCID: PMC2683808  PMID: 19393051

Results 1-3 (3)