• Changes in Estimated Glomerular Filtration Rate Over Time in South African HIV-1-Infected Patients Receiving Tenofovir: a Retrospective Cohort Study

      De Waal, R; Cohen, K; Fox, MP; Stinson, K; Maartens, G; Boulle, A; Igumbor, EU; Davies, MA (International AIDS Society, 2017-04-10)
      Tenofovir has been associated with decline in kidney function, but in patients with low baseline kidney function, improvements over time have been reported. Additionally, the magnitude and trajectory of estimated glomerular filtration rate (eGFR) changes may differ according to how eGFR is calculated. We described changes in eGFR over time, and the incidence of, and risk factors for, kidney toxicity, in a South African cohort.
    • First-Line Antiretroviral Drug Discontinuations in Children

      Fortuin-de Smidt, M; de Waal, R; Cohen, K; Technau, KG; Stinson, K; Maartens, G; Boulle, A; Igumbor, EU; Davies, MA (Public Library of Science, 2017-02-13)
      There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.
    • Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa.

      Coetzee, D; Hildebrand, K; Boulle, A; Maartens, G; Louis, F; Labatala, V; Reuter, H; Ntwana, N; Goemaere, E; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa. (2004-04-09)
      BACKGROUND: A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. METHODS: Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count < 200 x 10 cells/l. The programme used standardized protocols (using generic medicines whenever possible), a team-approach to clinical care and a patient-centred approach to promote adherence. RESULTS: Two-hundred and eighty-seven adults naive to prior ART were followed for a median duration of 13.9 months. The median CD4 lymphocyte count was 43 x 10 cells/l at initiation of treatment, and the mean log10 HIV RNA was 5.18 copies/ml. The HIV RNA level was undetectable (< 400 copies/ml) in 88.1, 89.2, 84.2, 75.0 and 69.7% of patients at 3, 6, 12, 18 and 24 months respectively. The cumulative probability of remaining alive was 86.3% at 24 months on treatment for all patients, 91.4% for those with a baseline CD4 lymphocyte count > or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. CONCLUSIONS: ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.
    • Outcomes of nevirapine- and efavirenz-based antiretroviral therapy when coadministered with rifampicin-based antitubercular therapy

      Boulle, A; Van Cutsem, G; Cohen, K; Hilderbrand, K; Mathee, S; Abrahams, M; Goemaere, E; Coetzee, D; Maartens, G; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Médecins Sans Frontières, Cape Town, South Africa; Site B Community Health Centre, Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa (2008-08-06)
      CONTEXT: Rifampicin-based antitubercular therapy reduces the plasma concentrations of nevirapine and efavirenz. The virological consequences of these interactions are not well described. OBJECTIVE: To assess the effectiveness and tolerability of concomitant efavirenz- or nevirapine-based combination antiretroviral therapy and rifampicin-based antitubercular therapy. DESIGN, SETTING, AND PARTICIPANTS: Cohort analysis of prospectively collected routine clinical data in a community-based South African antiretroviral treatment program. Antiretroviral treatment-naive adults enrolled between May 2001 and June 2006 were included in the analysis, and were followed up until the end of 2006. INTERVENTIONS: Patients starting antiretroviral therapy with or without concurrent antitubercular therapy received either efavirenz or nevirapine at standard doses. Patients developing tuberculosis while taking antiretroviral therapy that included nevirapine were either changed to efavirenz or continued taking nevirapine. MAIN OUTCOME MEASURES: Viral load of 400 copies/mL or more after 6, 12, and 18 months of antiretroviral therapy; time to the first viral load of 400 copies/mL or more; time to confirmed virological failure (2 consecutive values > or = 5000 copies/mL); time to death; and time to treatment-limiting toxicity were assessed. RESULTS: The analysis included 2035 individuals who started antiretroviral therapy with efavirenz (1074 with concurrent tuberculosis) and 1935 with nevirapine (209 with concurrent tuberculosis). There were no differences in time to death or substitution of either antiretroviral drug for toxicity with and without concurrent tuberculosis. Patients starting nevirapine with concurrent tuberculosis were at a higher risk of elevated viral load most notably at 6 months (16.3%; 95% confidence interval [CI], 10.6%-23.5%) than those without tuberculosis (8.3%; 95% CI, 6.7%-10.0%; adjusted odds ratio [OR], 2.1; 95% CI, 1.2-3.4; and in the combined estimate, adjusted OR, 1.7; 95% CI, 1.2-2.6). In the time-to-event analysis of confirmed virological failure (2 consecutive values of > or = 5000 copies/mL), patients starting nevirapine with concurrent tuberculosis developed virological failure sooner (adjusted hazard ratio [HR] 2.2; 95% CI, 1.3-3.7). There were no differences between patients starting efavirenz with and without concurrent tuberculosis (adjusted OR, 1.1; 95% CI, 0.8-1.5 [combined estimate] and adjusted HR, 1.1; 95% CI, 0.6-2.0, respectively). There was no difference in time to virological rebound in patients free of tuberculosis and those developing tuberculosis during follow-up while taking nevirapine (adjusted HR, 1.0; 95% CI, 0.5-2.0) or efavirenz (adjusted HR, 0.8; 95% CI, 0.4-1.7). CONCLUSION: In this cohort study, virological outcomes were inferior when nevirapine-based antiretroviral therapy was commenced while taking antitubercular treatment (vs without concurrent tuberculosis) but comparable when starting efavirenz-based antiretroviral therapy (vs without concurrent tuberculosis) or when tuberculosis developed while taking established nevirapine- or efavirenz-based therapies.
    • Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort.

      Boulle, A; Orrell, C; Kaplan, R; Van Cutsem, G; McNally, M; Hilderbrand, K; Myer, L; Egger, M; Coetzee, D; Maartens, G; et al. (International Medical Press, 2007)
      INTRODUCTION: The patterns and reasons for antiretroviral therapy (ART) drug substitutions are poorly described in resource-limited settings. METHODS: Time to and reason for drug substitution were recorded in treatment-naive adults receiving ART in two primary care treatment programmes in Cape Town. The cumulative proportion of patients having therapy changed because of toxicity was described for each drug, and associations with these changes were explored in multivariate models. RESULTS: Analysis included 2,679 individuals followed for a median of 11 months. Median CD4+ T-cell count at baseline was 85 cells/microl. Mean weight was 59 kg, mean age was 32 years and 71% were women. All started non-nucleoside reverse transcriptase inhibitor-based ART (60% on efavrienz) and 75% started on stavudine (d4T). After 3 years, 75% remained in care on-site, of whom 72% remained on their initial regimen. Substitutions due to toxicity of nevirapine (8% by 3 years), efavirenz (2%) and zidovudine (8%) occurred early. Substitutions on d4T occurred in 21% of patients by 3 years, due to symptomatic hyperlactataemia (5%), lipodystrophy (9%) or peripheral neuropathy (6%), and continued to accumulate over time. Those at greatest risk of hyperlactataemia or lipodystrophy were women on ART > or =6 months, weighing > or =75 kg at baseline. DISCUSSION: A high proportion of adult patients are able to tolerate their initial ART regimen for up to 3 years. In most instances treatment-limiting toxicities occur early, but continue to accumulate over time in patients on d4T. Whilst awaiting other treatment options, the risks of known toxicities could be minimized through early identification of patients at the highest risk.