• Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - The IeDEA Southern Africa Collaboration.

      Davies, Mary-Ann; Boulle, Andrew; Eley, Brian; Moultrie, Harry; Technau, Karl; Rabie, Helena; van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Egger, Matthias; et al. (2011-08-11)
      Objectives  To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART). Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment. Results  Among 3115 children [median (interquartile range) age 48 (20-84) months at ART initiation] on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006, WHO 2010 and DHHS 2008 criteria, respectively. The corresponding positive predictive values (PPV) were 31%, 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008). Conclusion  Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify VF in children.
    • Growth in Virologically Suppressed HIV-Positive Children on Antiretroviral Therapy: Individual and Population-level References.

      Keiser, Olivia; Blaser, Nello; Davies, Mary-Ann; Wessa, Patrick; Eley, Brian; Moultrie, Harry; Rabie, Helena; Technau, Karl-Günther; Ndirangu, James; Garone, Daniela; et al. (2015-10)
      Combination antiretroviral therapy (ART) suppresses viral replication in HIV-infected children. The growth of virologically suppressed children on ART has not been well documented. We aimed to develop dynamic reference curves for weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ).
    • Incidence Rate of Kaposi Sarcoma in HIV-Infected Patients on Antiretroviral Therapy in Southern Africa: A Prospective Multicohort Study

      Rohner, Eliane; Valeri, Fabio; Maskew, Mhairi; Prozesky, Hans; Rabie, Helena; Garone, Daniela; Dickinson, Diana; Chimbetete, Cleophas; Lumano-Mulenga, Priscilla; Sikazwe, Izukanji; et al. (Lippincott Williams & Wilkins, 2014-12-15)
      The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa.
    • Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

      Cornell, Morna; Technau, Karl; Fairall, Lara; Wood, Robin; Moultrie, Harry; van Cutsem, Gilles; Giddy, Janet; Mohapi, Lerato; Eley, Brian; MacPhail, Patrick; et al. (2009-09)
      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.
    • Outcomes of the South African National Antiretroviral Treatment Programme for children: the IeDEA Southern Africa collaboration.

      Davies, Mary-Ann; Keiser, Olivia; Technau, Karl; Eley, Brian; Rabie, Helena; van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Boulle, Andrew; Egger, Matthias; et al. (2009-10)
      OBJECTIVES: To assess paediatric antiretroviral treatment (ART) outcomes and their associations from a collaborative cohort representing 20% of the South African national treatment programme. DESIGN AND SETTING: Multi-cohort study of 7 public sector paediatric ART programmes in Gauteng, Western Cape and KwaZulu-Natal provinces. SUBJECTS: ART-naive children (< or = 16 years) who commenced treatment with > or = 3 antiretroviral drugs before March 2008. OUTCOME MEASURES: Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART. RESULTS: The median (interquartile range) age of 6 078 children with 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% being < 18 months. Most were severely ill at ART initiation. More than 75% of children were appropriately monitored at 6-monthly intervals with viral load suppression (< 400 copies/ml) being 80% or above throughout 36 months of treatment. Mortality and retention in care at 3 years were 7.7% (95% confidence interval 7.0 - 8.6%) and 81.4% (80.1 - 82.6%), respectively. Together with young age, all markers of disease severity (low weight-for-age z-score, high viral load, severe immune suppression, stage 3/4 disease and anaemia) were independently associated with mortality. CONCLUSIONS: Dramatic clinical benefit for children accessing the national ART programme is demonstrated. Higher mortality in infants and those with advanced disease highlights the need for early diagnosis of HIV infection and commencement of ART.
    • Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

      Davies, Mary-Ann; Phiri, Sam; Wood, Robin; Wellington, Maureen; Cox, Vivian; Bolton-Moore, Carolyn; Timmerman, Venessa; Moultrie, Harry; Ndirangu, James; Rabie, Helena; et al. (Public Library of Science, 2013-12-09)
    • Variability of Growth in Children Starting Antiretroviral Treatment in Southern Africa

      Gsponer, Thomas; Weigel, Ralf; Davies, Mary-Ann; Bolton, Carolyn; Moultrie, Harry; Vaz, Paula; Rabie, Helena; Technau, Karl; Ndirangu, James; Eley, Brian; et al. (American Academy of Pediatrics, 2012-10)
      Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa.
    • Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

      Davies, Mary-Ann; Moultrie, Harry; Eley, Brian; Rabie, Helena; Van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Technau, Karl; Keiser, Olivia; Egger, Matthias; et al. (Lippincott Williams & Wilkins, 2011-03-01)
      With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa.