• A Drug Dosage Table is a Useful Tool to Facilitate Prescriptions of Antiretroviral Drugs for Children in Thailand.

      Ponnet, M; Frederix, K; Petdachai, W; Wilson, D; Eksaengsri, A; Zachariah, R; Médecins Sans Frontières, Bangkok, Thailand. (2005-06)
      Scaling up of antiretroviral treatment (ART) for children in countries like Thailand will require decentralization and management by non-specialist doctors. We describe (a) the formulation of a standardized drug dosage table to facilitate antiretroviral drug (ARV) prescriptions for children, (b) the acceptability of such a table among doctors and (c) the safety and efficacy of drug doses in the table. Acceptability was assessed using a questionnaire. Safety and efficacy were assessed on the basis of incidence of adverse effects and virological response to treatment, respectively. Of all doctors (n=18), 17 (94%) found that the table was practical to use, avoided miscalculations and made them more confident with prescriptions. Of 49 children prescribed ARVs, less than 5% had adverse side-effects. All ARV-naïve children achieved undetectable viral loads within six months of ART. In our setting, a standardized drug dosage table provided a simple and reliable tool that facilitated ARV prescriptions for children.
    • A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa

      Van Cutsem, G; Saphonn, V; Saramony, S; Vibol, U; Zhang, FJ; Han, N; Saghayam, S; Kurniati, N; Muktiarti, D; Fong, SM; et al. (BioMed Central, 2011-04-08)
      To better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts.
    • Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

      Fenner, Lukas; Brinkhof, Martin W G; Keiser, Olivia; Weigel, Ralf; Cornell, Morna; Moultrie, Harry; Prozesky, Hans; Technau, Karl; Eley, Brian; Vaz, Paula; et al. (2010-08-15)
      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.
    • Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

      Janssens, B; Raleigh, B; Soeung, S; Akao, K; Te, V; Gupta, J; Vun, M; Ford, N; Nouhin, J; Nerrienet, E; et al. (2007-11)
      OBJECTIVE: Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS: Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS: Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS: This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.
    • 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).
    • Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda.

      Ahoua, Laurence; Guenther, Gunar; Rouzioux, Christine; Pinoges, Loretxu; Anguzu, Paul; Taburet, Anne-Marie; Balkan, Suna; Olson, David M; Olaro, Charles; Pujades-Rodríguez, Mar; et al. (BioMed Central, 2011-07-26)
      Children living with HIV continue to be in urgent need of combined antiretroviral therapy (ART). Strategies to scale up and improve pediatric HIV care in resource-poor regions, especially in sub-Saharan Africa, require further research from these settings. We describe treatment outcomes in children treated in rural Uganda after 1 and 2 years of ART start.
    • Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa.

      Murphy, R A; Sunpath, H; Taha, B; Kappagoda, S; Maphasa, K T M; Kuritzkes, D R; Smeaton, L; Doctors Without Borders USA, New York, USA; McCord Hospital, South Africa; Harvard Medical School, Massachusetts, USA; Division of Infectious Disease and Geographic Medicine, California, USA; Zoe-Life, South Africa; Section of Retroviral Therapeutics, Massachusetts, USA; Centre for Biostatistics in AIDS Research, Massachusetts, USA (2010-07-01)
      A prospective cohort study was conducted among human immunodeficiency virus (HIV) infected in-patients with tuberculosis (TB) or other opportunistic infections (OIs) in South Africa to estimate subsequent antiretroviral therapy (ART) uptake and survival.
    • 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.
    • Paediatric HIV care in sub-Saharan Africa: clinical presentation and 2-year outcomes stratified by age group

      Ben-Farhat, Jihane; Gale, Marianne; Szumilin, Elisabeth; Balkan, Suna; Poulet, Elisabeth; Pujades-Rodríguez, Mar (John Wiley & Sons Ltd, 2013-09)
      To examine age differences in mortality and programme attrition amongst paediatric patients treated in four African HIV programmes.
    • Scaling-up co-trimoxazole prophylaxis in HIV-exposed and HIV-infected children in high HIV-prevalence countries.

      Zachariah, R; Harries, A D; Luo, C; Bachman, G; Graham, S M; Médecins Sans Frontières, Medical department (Operational Research), Brussels Operational Center, Brussels, Belgium. zachariah@internet.lu (Elsevier, 2007-10)
      Co-trimoxazole (trimethoprim-sulfamethoxazole) is a widely available antibiotic that substantially reduces HIV-related morbidity and mortality in both adults and children. Prophylaxis with co-trimoxazole is a recommended intervention of proven benefit that could serve not only as an initial step towards improving paediatric care in young children with limited access to antiretroviral treatment, but also as an important complement to antiretroviral therapy in resource-limited settings. Despite co-trimoxazole's known clinical benefits, the potential operational benefits, and favourable recommendations by WHO, UNAIDS, and UNICEF, its routine use in developing countries--particularly sub-Saharan Africa--has remained limited. Out of an estimated 4 million children in need of co-trimoxazole prophylaxis (HIV-exposed and HIV-infected), only 4% are currently receiving this intervention. We discuss some of the major barriers preventing the scale-up of co-trimoxazole prophylaxis for children in countries with a high prevalence of HIV and propose specific actions required to tackle these challenges.
    • Treatment Outcomes Stratified by Baseline Immunological Status Among Young Children Receiving Nonnucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Resource-Limited Settings.

      O'Brien, D P; Sauvageot, D; Olson, D; Schaeffer, M; Humblet, P; Pudjades, M; Ellman, T; Zachariah, R; Szumilin, E; Arnould, L; et al. (Published by: Infectious Diseases Society of America, 2007-05-01)
      A study of 568 children aged <5 years who commenced nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in resource-limited settings revealed good early outcomes. After 12 months of antiretroviral therapy, survival probability was 0.89 (95% confidence interval, 0.86-0.92), with no significant difference among children stratified on the basis of baseline immunological levels; 62% attained a CD4 cell percentage >25%, and 7% continued to have a CD4 cell percentage <15%.
    • 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.
    • Viral Load Versus CD4⁺ Monitoring and 5-Year Outcomes of Antiretroviral Therapy in HIV-Positive Children in Southern Africa: a Cohort-Based Modelling Study

      Salazar-Vizcaya, L; Keiser, O; Karl, T; Davies, MA; Haas, Andreas D; Blaser, N; Cox, V; Eley, B; Rabie, H; Moultrie, H; et al. (Lippincott Williams & Wilkins, 2014-10-23)
      Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4⁺ to monitor ART. We assessed the benefit of replacing CD4⁺ by viral load monitoring.
    • 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.
    • Voluntary Counselling, HIV Testing and Adjunctive Cotrimoxazole Reduces Mortality in Tuberculosis Patients in Thyolo, Malawi.

      Zachariah, R; Spielmann M P; Chinji, C; Gomani, P; Arendt, V; Hargreaves, N J; Salaniponi, F M L; Harries, A D; Medecins Sans Frontieres-Luxembourg, Blantyre, Malawi. zachariah@internet.Lu (2003-05-02)
      OBJECTIVES: To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi. DESIGN: 'Before' and 'after' cohort study using historical controls. METHODS: Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group). FINDINGS: A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5. INTERPRETATION: This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions.