• Generic Fixed-Dose Combination Antiretroviral Treatment in Resource-Poor Settings: Multicentric Observational Cohort

      Calmy, A; Pinoges, L; Szumilin, E; Zachariah, R; Ford, N; Ferradini, L; MSF, Campaign for Access to Essential Medicines, 78 rue de Lausanne, 1205 Geneva, Switzerland. acalmy@stvincents.com.au (2006-05-12)
      BACKGROUND: The use fixed-dose combination (FDC) is a critical tool in improving HAART. Studies on the effectiveness of combined lamivudine, stavudine and nevirapine (3TC/d4T/NVP) are scarce. OBJECTIVE: To analyse 6861 patients in a large observational cohort from 21 Médecins Sans Frontieres (MSF) HIV/AIDS programmes taking 3TC/d4T/NVP, with subcohort analyses of patients at 12 and 18 months of treatment. METHODS: Survival was analysed using Kaplan-Meier method and factors associated with progression to death with Cox proportional hazard ratio. RESULTS: Median baseline CD4 cell count at initiating of FDC was 89 cells/microl [interquartile range (IQR), 33-158]. The median follow-up time was 4.1 months (IQR, 1.9-7.3). The incidence rate of death during follow-up was 14.2/100 person-years [95% confidence interval (CI), 13.8-14.5]. Estimates of survival (excluding those lost to follow-up) were 0.93 (95% CI, 92-94) at 6 months (n = 2,231) and 0.90 (95% CI, 89-91) at 12 months (n = 472). Using a Cox model, the following factors were associated with death: male gender, symptomatic infection, body mass index < 18 kg/m and CD4 cell count 15-50 cells/microl or < 15 cells/microl. Subcohort analysis of 655 patients after 1 year of follow-up (M12 FDC cohort) revealed that 77% remained on HAART, 91% of these still on the FDC regimen; 5% discontinued the FDC because of drug intolerance. At 18 months, 77% of the patients remained on HAART. CONCLUSIONS: Positive outcomes for d4T/3TC/NVP are reported for up to 18 months in terms of efficacy and safety.
    • Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia.

      Madec, Y; Laureillard, D; Pinoges, L; Fernandez, M; Prak, N; Ngeth, C; Moeung, S; Song, S; Balkan, S; Ferradini, L; et al. (2007-01-30)
      BACKGROUND: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. METHODS: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. RESULTS: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. CONCLUSION: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.
    • Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

      Ahoua, L; Guenther, G; Pinoges, L; Anguzu, P; Chaix, M L; Le Tiec, C; Balkan, S; Olson, D; Olaro, C; Pujades-Rodriguez, M; et al. (2009-06-03)
      ABSTRACT: BACKGROUND: Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. METHODS: Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/mL) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression. RESULTS: At 12 and 24 months of ART, 72% (n=701) and 70% (n=369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/mL). Risk factors for virological failure (>1,000 copies/mL) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. CONCLUSIONS: Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.