Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting

Incidence of Kaposi Sarcoma in HIV-infected patients – a prospective multi-cohort study from Southern Africa

Oral presentation presented at the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI) Bethesda, MD, USA. 7-8 November 2011The original publication is available at http://www.infectagentscancer.com/content/7/S1/O20Background: The incidence of Kaposi Sarcoma (KS) is high in sub-Saharan Africa. Data on KS among HIV-infected patients receiving and not yet receiving antiretroviral therapy (ART) are, however, scarce in Africa. Within the framework of a large multi-cohort project, the International epidemiologic Database to Evaluate AIDS (IeDEA), we estimate the incidence and risk factors for the development of KS in HIV-infected patients in Southern Africa.Publishers' Versio

Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study.

Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART

The Impact of Delayed Switch to Second-Line Antiretroviral Therapy on Mortality, Depending on Definition of Failure Time and CD4 Count at Failure

Little is known about the functional relationship of delaying second-line treatment initiation for human immunodeficiency virus–positive patients and mortality, given a patient’s immune status. We included 7,255 patients starting antiretroviral therapy during 2004–2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting of marginal structural models. The nonlinear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation. We adjusted for measured time-varying confounding by CD4 count, viral load, and visit frequency. Five-year mortality was estimated to be 10.5% (95% CI: 2.2, 18.8) for immediate switch and to be 26.6% (95% CI: 20.9, 32.3) for no switch (51.1% if CD4 count was <100 cells/mm3). The hazard of death was estimated to be 0.37 (95% CI: 0.30, 0.46) times lower if everyone had been switched immediately compared with never. The shorter the delay in switching, the lower the hazard of death—delaying 30–59 days reduced the hazard by 0.53 (95% CI: 0.43, 0.65) times and 60–119 days by 0.58 (95% CI: 0.49, 0.69) times, compared with no switch. Early treatment switch is particularly important for patients with low CD4 counts at failure

Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level

Tenofovir in second-line ART in Zambia and South Africa: collaborative analysis of cohort studies

Tenofovir (TDF) is increasingly used in second-line antiretroviral treatment (ART) in sub-Saharan Africa. We compared outcomes of second-line ART containing and not containing TDF in cohort studies from Zambia and the Republic of South Africa (RSA)

Monitoring the South African National Antireteoviral Treatment Programme, 2003-2007: The IeDEA Southern Africa Collaboration

Objectives: To introduce the combined South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterize patients accessing these services; and to describe changes in services and patients 2003-2007. Design & setting Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. Subjects ART-naïve adults and children (<16 years old) who initiated ART with ≥3 antiretroviral drugs before 2008. Results: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median (IQR) range was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5) respectively. Of adults, 68% were female. Median CD4 cell count was 102 cells/µL (44-164) and was lower among males than females (86, 34-150 vs 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/µL, p<0.001) and for those in Stage IV (39-89 cells/µL, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5%-16.0%, p<0.001). Conclusions: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increasing enrolment. Late presentation, especially of men and children, remains a concern. Investment in sentinel sites ensures good individual-level data while freeing most sites to continue with simplified reporting

Assessing the association between changing NRTIs when initiating second-line ART and treatment outcomes.

BACKGROUND After first-line antiretroviral therapy (ART) failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second-line is uncertain due to the high potency of protease inhibitors used in second-line. SETTING We used clinical data from 6,290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS-Southern Africa cohort. METHODS We included patients who initiated on standard first-line ART and had evidence of first-line failure. We used propensity score-adjusted Cox proportional hazards models to evaluate the impact of change in NRTI on second-line failure compared to remaining on the same NRTI in second-line. In South Africa, where viral load monitoring was available, treatment failure was defined as two consecutive viral loads >1,000 copies/mL. In Zambia, it was defined as two consecutive CD4 counts <100 cells/mm. RESULTS Among patients in South Africa initiated on zidovudine, the adjusted hazard ratio for second-line virologic failure was 0.25 (95% CI: 0.11, 0.57) for those switching to tenofovir vs. remaining on zidovudine. Among patients in South Africa initiated on tenofovir, switching to zidovudine in second-line was associated with reduced second-line failure (adjusted hazard ratio = 0.35 [95% CI: 0.13, 0.96]). In Zambia where viral load monitoring was not available, results were less conclusive. CONCLUSION Changing NRTI in second-line was associated with better clinical outcomes in South Africa. Additional clinical trial research regarding second-line NRTI choices for patients initiated on tenofovir or with contraindications to specific NRTIs is needed

CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517-541] in North America, 494/µl (95% CI: 429-559) in West Africa, 515/µl (95% CI: 508-522) in Southern Africa, 503/µl (95% CI: 478-528) in Asia and 437/µl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional leve