HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa.

OBJECTIVES: Urban and rural HIV treatment programmes face different challenges in the long-term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison. METHODS: HIV drug resistance data and associated treatment and monitoring information for adult patients failing first-line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared. RESULTS: Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/µL, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first-line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second-line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration. CONCLUSIONS: The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first-line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second-line regimen.

Time to eligibility for antiretroviral therapy in adults with CD4 cell count > 500 cells/µL in rural KwaZulu-Natal, South Africa.

OBJECTIVES: Understanding of progression to antiretroviral therapy (ART) eligibility and associated factors remains limited. The objectives of this analysis were to determine the time to ART eligibility and to explore factors associated with disease progression in adults with early HIV infection. METHODS: HIV-infected adults (≥ 18 years old) with CD4 cell count > 500 cells/µl were enrolled in the study at three primary health care clinics, and a sociodemographic, behavioural and partnership-level questionnaire was administered. Participants were followed 6-monthly and ART eligibility was determined using a CD4 cell count threshold of 350 cells/µl. Kaplan - Meier and Cox proportional hazard regression modelling were used in the analysis. RESULTS: A total of 206 adults contributed 381 years of follow-up; 79 (38%) reached the ART eligibility threshold. Median time to ART eligibility was shorter for male patients (12.0 months) than for female patients (33.9 months). Male sex [adjusted hazard ratio (aHR) 3.13; 95% confidence interval (CI) 1.82-5.39], residing in a household with food shortage in the previous year (aHR 1.58; 95% CI 0.99-2.54), and taking nutritional supplements in the first 6 months after enrolment (aHR 2.06; 95% CI 1.11-3.83) were associated with shorter time to ART eligibility. Compared with reference CD4 cell count ≤ 559 cells/µl, higher CD4 cell count was associated with longer time to ART eligibility [aHR 0.46 (95% CI 0.25-0.83) for CD4 cell count 560-632 cells/µl; aHR 0.30 (95% CI 0.16-0.57) for CD4 cell count 633-768 cells/µl; and aHR 0.17 (95% CI 0.08-0.38) for CD4 cell count > 768 cells/µl]. CONCLUSIONS: Over one in three adults with CD4 cell count > 500 cells/µl became eligible for ART at a CD4 cell count threshold of 350 cells/µl over a median of 2 years. The shorter time to ART eligibility in male patients suggests a possible need for sex-specific pre-ART care and monitoring strategies.

Combined antiretroviral and anti-tuberculosis drug resistance following incarceration.

We describe a case of HIV/tuberculosis (TB) co-infection from KwaZulu-Natal, South Africa, characterised by drug resistance in both pathogens. The development of drug resistance was linked temporally to two periods of incarceration. This highlights the urgent need for improved integration of HIV/TB control strategies within prison health systems and within the broader public health framework.

Are subtype differences important in HIV drug resistance?

The diversity of human immunodeficiency virus type 1 (HIV-1) has given rise to multiple subtypes and recombinant strains. The majority of research into antiretroviral agents and drug resistance has been performed on subtype B viruses, yet non-subtype B strains are responsible for 90% of global infections. Although it seems that combination antiretroviral regimens are effective against all HIV-1 subtypes, there is emerging evidence of subtype differences in drug resistance, relevant to antiretroviral strategies in different parts of the world. For this purpose, extensive sampling of HIV genetic diversity, curation and analyses are required to inform antiretroviral strategies in different parts of the world.

Community-based treatment for multidrug-resistant tuberculosis in rural KwaZulu-Natal, South Africa.

SETTING: Hlabisa health sub-district, KwaZulu-Natal, South Africa. OBJECTIVE: To describe the establishment of a community-based multidrug-resistant tuberculosis (MDR-TB) treatment programme embedded in the district TB control programme and to evaluate whether early outcomes are comparable to those in the traditional hospital-based model of care. DESIGN: Cases who initiated community-based MDR-TB treatment (CM) between March and December 2008 were compared with patients who initiated MDR-TB treatment under the traditional hospital-based model of care (TM) between January 2001 and February 2008. Time to initiation of treatment and time to sputum smear and culture conversion were compared for the two groups in Kaplan-Meier survival curves using the Mantel-Cox log-rank test. RESULTS: Overall, 50 CM cases and 57 TM cases were included; 39 of the 50 CM cases (78.0%) were human immunodeficiency virus positive. The median time to initiation of treatment was 84 days for CM and 106.5 days for TM (P = 0.002). Median time to sputum smear conversion was shorter for CM than TM (59 vs. 92 days, P = 0.055), as was time to sputum culture conversion (85 vs. 119 days, P = 0.002). CONCLUSION: Community-based treatment for MDR-TB can be implemented within the existing TB control programme in rural South Africa and should be scaled up where resources allow.

Scale-up of a decentralized HIV treatment programme in rural KwaZulu-Natal, South Africa: does rapid expansion affect patient outcomes?

Objective:To describe the scale-up of a decentralized HIV treatment programme delivered through the primary health care system in rural KwaZulu-Natal, South Africa, and to assess trends in baseline characteristics and outcomes in the study population Methods The programme started delivery of antiretroviral therapy (ART) in October 2004. Information on all patients initiated on ART was captured in the programme database and follow-up status was updated monthly. All adult patients (≥ 16 years) who initiated ART between October 2004 and September 2008 were included and stratified into 6-month groups. Clinical and sociodemographic characteristics were compared between the groups. Retention in care, mortality, loss to follow-up and virological outcomes were assessed at 12 months post-ART initiation.Findings A total of 5719 adults initiated on ART were included (67.9% female). Median baseline CD4+ lymphocyte count was 116 cells/µl (interquartile range, IQR: 53­173). There was an increase in the proportion of women who initiated ART while pregnant but no change in other baseline characteristics over time. Overall retention in care at 12 months was 84.0% (95% confidence interval, CI: 82.6­85.3); 10.9% died (95% CI: 9.8­12.0); 3.7% were lost to follow-up (95% CI: 3.0­4.4). Mortality was highest in the first 3 months after ART initiation: 30.1 deaths per 100 person­years (95% CI: 26.3­34.5). At 12 months 23.0% had a detectable viral load (> 25 copies/ml) (95% CI: 19.5­25.5).Conclusion Outcomes were not affected by rapid expansion of this decentralized HIV treatment programme. The relatively high rates of detectable viral load highlight the need for further efforts to improve the quality of services