• Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared.

      Keiser, O; Orrell, C; Egger, M; Wood, R; Brinkhof, M W G; Furrer, H; Van Cutsem, G; Ledergerber, B; Boulle, A; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. (PLoS, 2008-07-08)
      BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
    • The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure.

      Davies, M-A; Boulle, A; Technau, K; Eley, B; Moultrie, H; Rabie, H; Garone, D; Giddy, J; Wood, R; Egger, M; et al. (2012-09-14)
      Objectives  To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. 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. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results  Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion  The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.
    • 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.
    • 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 response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.

      Nyakato, P; Schomaker, M; Sipambo, N; Technau, KG; Fatti, G; Rabie, H; Tanser, F; Eley, B; Euvrard, J; Wood, R; et al. (Lippincott, Williams & Wilkins, 2021-01-21)
      Background and objectives: Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with nonperinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence. Design: A retrospective cohort study Methods: We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004–2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs. Results: We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a nonnucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex. Conclusions: As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.
    • Where do HIV-infected adolescents go after transfer? - Tracking transition/transfer of HIV-infected adolescents using linkage of cohort data to a health information system platform

      Davies, MA; Tsondai, P; Tiffin, N; Eley, B; Rabie, H; Euvrard, J; Orrell, C; Prozesky, H; Wood, R; Cogill, D; et al. (Wiley, 2017-03-16)
      To evaluate long-term outcomes in HIV-infected adolescents, it is important to identify ways of tracking outcomes after transfer to a different health facility. The Department of Health (DoH) in the Western Cape Province (WCP) of South Africa uses a single unique identifier for all patients across the health service platform. We examined adolescent outcomes after transfer by linking data from four International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) cohorts in the WCP with DoH data.