• 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.
    • 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.
    • Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières

      Pujades-Rodriguez, M; O'Brien, D; Humblet, P; Calmy, A; Epicentre, Paris, France; Médecins Sans Frontières, Paris, France; Campaign for Access to Essential Medicines, Geneva, Switzerland (2008-07-11)
      OBJECTIVES: To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. DESIGN/METHODS: We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. RESULTS: Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. CONCLUSION: The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.
    • Simplifying and adapting antiretroviral treatment in resource-poor settings: a necessary step to scaling-up.

      Calmy, A; Klement, E; Teck, R; Berman, D; Pécoul, B; Ferradini, L (Wolters Kluwer, 2004-12-03)
    • Sustaining Access to Antiretroviral Therapy in the Less-Developed World: Lessons from Brazil and Thailand.

      Ford, N; Wilson, D; Costa Chaves, G; Lotrowska, M; Kijtiwatchakul, K; Médecins Sans Frontières, 522 Mooban Nakorn Thai 14, Ladphrao Soi 101/1, Bangkok 10240, Thailand. nathan.ford@london.msf.org (2007-07)
      ANTIRETROVIRAL ROLLOUT IN BRAZIL AND THAILAND: Brazil and Thailand are among few developing countries to achieve universal access to antiretroviral therapy. Three factors were critical to this success: legislation for free access to treatment; public sector capacity to manufacture medicines; and strong civil society action to support government initiatives to improve access. LOCAL PRODUCTION OF AFFORDABLE, NON-PATENTED DRUGS: Many older antiretroviral drugs are not patented in either country and affordable generic versions are manufactured by local pharmaceutical institutes. EFFORTS TO ENSURE ACCESS TO EXPENSIVE, PATENTED DRUGS: Developing countries were not required to grant patents on medicines until 2005, but under US government threats of trade sanctions, Thailand and Brazil began doing so at least ten years prior to this date. Brazil has used price negotiations with multi-national pharmaceutical companies to lower the price of newer patented antiretrovirals. However, the prices obtained by this approach remain unaffordable. Thailand recently employed compulsory licensing for two antiretrovirals, obtaining substantial price reductions, both for generic and brand products. Following Thailand's example, Brazil has issued its first compulsory license. LESSONS LEARNED: Middle-income countries are unable to pay the high prices of multinational pharmaceutical companies. By relying on negotiations with companies, Brazil pays up to four times more for some drugs compared with prices available internationally. Compulsory licensing has brought treatment with newer antiretrovirals within reach in Thailand, but has resulted in pressure from industry and the US government. An informed and engaged civil society is essential to support governments in putting health before trade.
    • 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; et al. (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.
    • Treating HIV in the developing world: getting ahead of the drug development curve.

      Ford, N; Calmy, A; von Schoen-Angerer, T (Elsevier, 2007-01)
    • Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.

      Pujades-Rodríguez, Mar; Balkan, Suna; Arnould, Line; Brinkhof, Martin A W; Calmy, Alexandra; Epicentre, Médecins Sans Frontières 42-bis, Bd, 8 rue Saint Sabin, 75011 Paris, France. mar.pujades@epicentre.msf.org (2010-07-21)
      CONTEXT: Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. OBJECTIVES: To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. DESIGN, SETTING, AND PARTICIPANTS: Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. MAIN OUTCOME MEASURES: Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. RESULTS: The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. CONCLUSIONS: Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.
    • Treatment outcomes of patients on Second-line Antiretroviral Therapy in resource-limited settings: A Systematic Review and Meta-Analysis

      Ajose, Olawale; Mookerjee, Siddharth; Mills, Edward J; Boulle, Andrew; Ford, Nathan; Clinton Health Access Initiative, Dar es Salaam, Tanzania. (2012-05-15)
      A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings.
    • 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%.
    • Universal access in the fight against HIV/AIDS

      Girard, Françoise; Ford, Nathan; Montaner, Julio; Cahn, Pedro; Katabira, Elly; Open Society Institute Public Health Program, New York, NY, USA; Médecins Sans Frontières, Cape Town, South Africa; Division of AIDS, University of British Columbia, Vancouver, BC, Canada; Fundacion Huesped, Buenos Aires, Argentina; Department of Research, Makerere Medical School, Kampala, Uganda. (2010-07-09)
    • Village-based AIDS prevention in a rural district in Uganda.

      Schopper, D; Doussantousse, S; Ayiga, N; Ezatirale, G; Idro, W J; Homsy, J; Médecins Sans Frontières, Geneva, Switzerland. (Oxford Journals, 1995-06)
      OBJECTIVE: To design, implement and evaluate a village-based AIDS prevention programme in a rural district in north-western Uganda. A baseline KAP survey of the general population was carried out to design a district-wide information campaign and condom promotion programme. Eighteen months later the impact achieved was measured through a second KAP survey, using the same methodology. METHODS: Anonymous structured interviews were conducted in March 1991 and October 1992 with 1486 and 1744 randomly selected individuals age 15-49, respectively. RESULTS: At 18 months, 60% of respondents had participated in an information session in the past year (47% women, 71% men) and 42% had received a pamphlet about AIDS (26% women, 58% men). Knowledge about AIDS, high initially (94%), reached 98%. More respondents knew that the incubation period is longer than one year (from 29% to 40%), and were willing to take care of a PWA (from 60% to 77%). Knowledge about condoms increased from 26 to 63% in women and 57 to 91% in men. Ever use of condoms among persons having engaged in casual sex in the past year increased from 6 to 33% in women, and 27 to 48% in men. Fifty per cent of condom users criticized lack of regular access to condoms. CONCLUSIONS: This is the first documented example of the impact a village-based AIDS prevention programme can achieve in a rural African community. Critical areas to be improved were identified, such as: women must be given better access to information, more attention must be paid to explain the asymptomatic state of HIV infection in appropriate terms, and condom social marketing must be developed.