• HIV and tuberculosis--science and implementation to turn the tide and reduce deaths.

      Harries, Anthony D; Lawn, Stephen D; Getahun, Haileyesus; Zachariah, Rony; Havlir, Diane V; International Union Against Tuberculosis and Lung Disease, Paris, France. adharries@theunion.org (2012-10)
      Every year, HIV-associated tuberculosis (TB) deprives 350,000 mainly young people of productive and healthy lives.People die because TB is not diagnosed and treated in those with known HIV infection and HIV infection is not diagnosed in those with TB. Even in those in whom both HIV and TB are diagnosed and treated, this often happens far too late. These deficiencies can be addressed through the application of new scientific evidence and diagnostic tools.
    • 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; Wood, R; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. andrew.boulle@uct.ac.za (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.
    • Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

      Keiser, Olivia; Tweya, Hannock; Boulle, Andrew; Braitstein, Paula; Schecter, Mauro; Brinkhof, Martin W G; Dabis, François; Tuboi, Suely; Sprinz, Eduardo; Pujades-Rodriguez, Mar; Calmy, Alexandra; Kumarasamy, Nagalingeswaran; Nash, Denis; Jahn, Andreas; MacPhail, Patrick; Lüthy, Ruedi; Wood, Robin; Egger, Matthias; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. (2009-09-10)
      In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.
    • Time to AIDS from 1992 to 1999 in HIV-1-Infected Subjects with Known Date of Infection.

      Tassie, J M; Grabar, S; Lancar, R; Deloumeaux, J; Bentata, M; Costagliola, D; Institut National de la Santé et de la Recherche Médicale SC4, Faculté de Médecine, St. Antoine Université Pierre et Marie Curie, Paris, France; Epicentre, Paris, France. (2002-05-01)
      To estimate the change in AIDS incubation time during three periods characterized by different availability of antiretroviral treatments, data from the French Hospital Database on HIV of 4702 HIV-1-positive subjects with a documented date of infection were analyzed. Times from seroconversion to AIDS were compared in three periods: period 1 from January 1992 to June 1995 (monotherapy); period 2 from July 1995 to June 1996 (dual therapy); and period 3 from July 1996 to June 1999 (triple therapy). Nonparametric survival analyses were performed to account for staggered entries in the database and during each period. From periods 1 to 3, antiretroviral treatments were initiated earlier after infection, more subjects were treated, and the nature of regimens changed (25.6% of subjects were treated with monotherapy in period 1, 34.6% were treated with dual therapy in period 2, and 53.4% were treated with triple therapy in period 3). Compared with period 1, the relative hazard (RH) of AIDS was 0.31 in period 3 (95% confidence interval [CI]: 0.24-0.39). When comparing period 3 with period 2, the RH of AIDS was 0.36 (CI: 0.29-0.45). Assuming a log normal distribution, the median time to AIDS was estimated as 8.0 years in period 1 (CI: 6.0-10.6), 9.8 years in period 2 (CI: 8.5, 11.2), and 20.0 years in period 3 (CI: 17.1-23.3). This lengthening in time to AIDS from 1992 to 1999 was particularly marked in the period after the introduction of triple therapy, including protease inhibitors.
    • Time to initiation of antiretroviral therapy among patients with HIV-associated tuberculosis in Cape Town, South Africa

      Lawn, Stephen D; Campbell, Lucy; Kaplan, Richard; Boulle, Andrew; Cornell, Morna; Kerschberger, Bernhard; Morrow, Carl; Little, Francesca; Egger, Matthias; Wood, Robin; The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; Department of Statistical Sciences, Faculty of Science, University of Cape Town, South Africa; School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Medecins Sans Frontieres, Cape Town, South Africa; Division of International and Environmental Health, Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland (Lippincott Williams & Wilkins, 2011-06-01)
      We studied the time interval between starting tuberculosis treatment and commencing antiretroviral treatment (ART) in HIV-infected patients (n = 1433; median CD4 count 71 cells per microliter, interquartile range: 32-132) attending 3 South African township ART services between 2002 and 2008. The overall median delay was 2.66 months (interquartile range: 1.58-4.17). In adjusted analyses, delays varied between treatment sites but were shorter for patients with lower CD4 counts and those treated in more recent calendar years. During the most recent period (2007-2008), 4.7%, 19.7%, and 51.1% of patients started ART within 2, 4, and 8 weeks of tuberculosis treatment, respectively. Operational barriers must be tackled to permit further acceleration of ART initiation as recommended by 2010 WHO ART guidelines.