• Association between older age and adverse outcomes on antiretroviral therapy: a cohort analysis of programme data from nine countries.

      Greig, Jane; Casas, Esther C; O'Brien, Daniel P; Mills, Edward J; Ford, Nathan; Médecins Sans Frontières, London, UK. jane.greig@london.msf.org (2012-07-31)
      Recent studies have highlighted the increased risk of adverse outcomes among older patients on antiretroviral therapy (ART). We report on the associations between older age and adverse outcomes in HIV/AIDS antiretroviral programmes across 17 programmes in sub-Saharan Africa.
    • AZT impairs immunological recovery on first-line ART: collaborative analysis of cohort studies in Southern Africa

      Wandeler, Gilles; Gsponer, Thomas; Mulenga, Lloyd; Garone, Daniela; Wood, Robin; Maskew, Mhairi; Prozesky, Hans; Hoffmann, Christopher; Ehmer, Jochen; Dickinson, Diana; Davies, Mary-Ann; Egger, Matthias; Keiser, Olivia; a.Division of International and Environmental Health, Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland b.Department of Infectious Diseases, University Hospital Bern, Bern, Switzerland c.Centre for Infectious Disease Research in Zambia, Lusaka, Zambia d.Khayelitsha ART Programme, Médecins Sans Frontières, Cape Town, South Africa e.The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa f.Themba Lethu, Johannesburg, South Africa g.Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa h.Aurum Institute for Health Research, Johannesburg, South Africa i.SolidarMed Lesotho, Lucerne, Switzerland j.HIV private practice, Gaborone, Botswana k.School of Public Health and Family Medicine, University of Cape Town, South Africa (Wolters Kluwer Health | Lippincott Williams & Wilkins, 2013-05-08)
      OBJECTIVES
    • Cascade of HIV Care and Population Biral Suppression in a High-Burden Region of Kenya

      Maman, D; Zeh, C; Mukui, I; Kirubi, B; Masson, S; Opolo, V; Szumilin, E; Riche, B; Etard, JF (Lippincott Williams & Wilkins, 2015-07-31)
      Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation - especially HIV incidence, population viral load, and ART eligibility - is rare in sub-Saharan Africa.
    • CD4+ cell count at antiretroviral therapy initiation and economic restoration in rural Uganda

      Venkataramani, Atheendar S; Thirumurthy, Harsha; Haberer, Jessica E; Boum, Yap; Siedner, Mark J; Kembabazi, Annet; Hunt, Peter W; Martin, Jeffrey N; Bangsberg, David R; Tsai, Alexander C (Lippincott Williams & Wilkins, 2014-01-08)
      To determine whether earlier initiation of antiretroviral therapy (ART) is associated with better economic outcomes.
    • Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

      Estill, Janne; Egger, Matthias; Blaser, Nello; Vizcaya, Luisa Salazar; Garone, Daniela; Wood, Robin; Campbell, Jennifer; Hallett, Timothy B; Keiser, Olivia; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. jestill@ispm.unibe.ch (Wolters Kluwer Lippincott Williams & Wilkins, 2013-06-01)
      Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa.
    • Early initiation of antiretroviral therapy and associated reduction in mortality, morbidity and defaulting in a nurse-managed, community cohort in Lesotho.

      Ford, Nathan; Kranzer, Katharina; Hilderbrand, Katherine; Jouquet, Guillaume; Goemaere, Eric; Vlahakis, Nathalie; Triviño, Laura; Makakole, Lipontso; Bygrave, Helen; Médecins Sans Frontières, University of Cape Town, South Africa. Nathan.ford@msf.org (2010-11-13)
      INTRODUCTION: The latest WHO guidelines recommend initiating antiretroviral therapy (ART) at CD4 cell counts less than 350 cells/μl. However, donors and national governments are reluctant to support implementation owing to uncertainty regarding feasibility and relative benefit. Lesotho has supported earlier initiation since 2008. We assessed outcomes comparing early (CD4 cell counts >200 cells/μl) and late (CD4 cell counts ≤200 cells/μl) initiation. METHODS: We describe survival probability among patients initiating ART at CD4 cell counts 200 or less and more than 200 cells/μl and assess associations between baseline CD4 cell counts and mortality, morbidity, loss to follow-up and hospitalization using Cox regression adjusting for confounders identified a priori. RESULTS: Our analysis included 1177 patients; median age was 38 years and the majority (67%) were women. Median time on ART for the overall cohort was 506 days (interquartile range 396-608). Five hundred and thirty eight patients initiated ART at a CD4 cell count 200 cells/μl or less (interquartile range 54-160) and 639 patients initiated at CD4 cell count more than 200 cells/μl (interquartile range 238-321). In multivariate analysis, we found that patients initiating at CD4 cell count more than 200 cells/μl were 68% less likely to die (adjusted hazard ratio 0.32, 95% confidence interval 0.20-0.50), and 39% less likely to be lost to follow-up (adjusted hazard ratio 0.61, 95% confidence interval 0.43-0.87). Initiating ART at CD4 cell count more than 200 cells/μl was also associated with a 27% reduction in the rate of incident morbidity (adjusted hazard ratio 0.73, 95% confidence interval 0.65-0.82) and a 63% decreased rate of hospitalization (adjusted hazard ratio 0.37, 95% confidence interval 0.19-0.73). CONCLUSION: Earlier initiation is feasible in a low resource, high HIV prevalence setting, and provides important benefits in terms of reduced mortality, morbidity, retention and hospitalization. Donors should fully support the implementation of the latest WHO recommendations.
    • Ensuring sustainable antiretroviral provision during economic crises.

      Mills, Edward J; Ford, Nathan; Nabiryo, Christine; Cooper, Curtis; Montaner, Julio; University of Ottawa, 451, Smyth Road, Ottawa, ON K1H 8M5, Canada. emills@cfenet.ubc.ca (2010-01-28)
    • 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.
    • Highly active antiretroviral therapy in resource-poor settings: the experience of Medecins Sans Frontieres

      Tassie, J M; Szumilin, E; Calmy, A; Goemaere, E; Medecins Sans Fronteres (2003-09)
      We describe the short-term results of highly active antiretroviral therapy (HAART) in seven projects in low and middle income countries. A total of 743 adults were included, and clinical, immunological and virological responses were analysed. At 6 months, outcomes were similar to those observed in western countries, and the probability of remaining on treatment was 94%. The challenge now is to extend access to HAART to the millions in urgent need.
    • Highly Active Antiretroviral Therapy in Resource-Poor Settings: The Experience of Médecins Sans Frontières.

      Tassie, J M; Szumilin, E; Calmy, A; Goemaere, E; Epicentre, Paris, France. (2003-09-05)
      We describe the short-term results of highly active antiretroviral therapy (HAART) in seven projects in low and middle income countries. A total of 743 adults were included, and clinical, immunological and virological responses were analysed. At 6 months, outcomes were similar to those observed in western countries, and the probability of remaining on treatment was 94%. The challenge now is to extend access to HAART to the millions in urgent need.
    • Involving Traditional Healers in AIDS Education and Counselling in Sub-Saharan Africa: A Review

      King, R; Homsy, J; Médecins Sans Frontières-Switzerland in Kampala, Uganda. (1997)
    • The marriage of science and optimized HIV care in resource-limited settings

      Calmy, A; Pizzocolo, C; Pizarro, L; Brücker, G; Murphy, R; Katlama, C; Strategies in Resource-Limited Settings Working Group; Campaign for Access to Essential Medicines, Médecins Sans Frontières, Geneva; Geneva University, Geneva, Switzerland; Solidarité Théapeutique et Initiatives contre le Sida, Paris; Université Paris 11, Faculté de Médicine Paris-Sud, Le Kremlin-Bicêtre, Paris; Université Pierre et Marie Curie, Paris, France (2008-11-12)
    • Mortality by baseline CD4 cell count among HIV patients initiating antiretroviral therapy: evidence from a large cohort in Uganda

      Mills, Edward J; Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Chan, Keith; Ford, Nathan; Hogg, Robert S; Cooper, Curtis; Faculty of Health Sciences, University of Ottawa, Ottawa, Canada; The AIDS Support Organization (TASO), Headquarters, Kampala, Uganda; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada; Médecins Sans Frontiers (MSF), Geneva, Switzerland; Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada (Lippincott Williams & Wilkins, 2011-03-27)
      Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan Africa are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda.
    • Moxifloxacin for Buruli ulcer/HIV coinfected patients: kill two birds with one stone?

      O'Brien, Daniel P; Comte, Eric; Ford, Nathan; Christinet, Vanessa; du Cros, Philipp; aManson Unit, Médecins Sans Frontières, London, UK bDepartment of Infectious Diseases, Geelong Hospital, Geelong cDepartment of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia dMedical Unit, Médecins Sans Frontières, Geneva, Switzerland eCenter for Infectious Diseases Epidemiology Research, University of Cape Town, Cape Town, South Africa fDepartment of HIV, University Hospitals of Geneva, Geneva, Switzerland. (2013-09-10)
    • 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.
    • Promoting adherence to antiretroviral therapy: the experience from a primary care setting in Khayelitsha, South Africa.

      Coetzee, D; Boulle, A; Hildebrand, K; Asselman, V; Van Cutsem, G; Goemaere, E; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. dcoetzee@phfm.uct.ac.za (2004-06)
      OBJECTIVE: To describe the approach used to promote adherence to antiretroviral therapy (ART) and to present the outcomes in the first primary care public sector ART project in South Africa. DESIGN: The study is a prospective open cohort, including all adult patients naive to previous ART who received antiretroviral treatment in Khayelitsha, from May 2001 to the end of 2002. Patients were followed until their most recent visit before 31 July 2003. METHODS: Plasma viral load was determined at 3, 6, 12, 18 and 24 months after ART was initiated, and CD4 cell counts 6-monthly. Kaplan-Meier estimates were determined for the cumulative proportions of patients surviving, and patients with viral load suppression and viral rebound. RESULTS: A total of 287 patients were initiated on triple therapy. The probability of survival was 86.3% at 24 months. The median CD4 cell count gain was 288 cells/microliters at 24 months. Viral load was less than 400 copies/ml in 89.2, 84.2 and 69.7% of patients at 6, 12 and 24 months, respectively. The cumulative probability of viral rebound (two consecutive HIV-RNA measurements above 400 copies/ml) after achieving an HIV-RNA measurement below 400 copies/ml was 13.2% at 18 months. CONCLUSION: The study shows that, with a standard approach to patient preparation and strategies to enhance adherence, a cohort of patients on ART can be retained in a resource-limited setting in a developing country. A high proportion of patients achieved suppression of viral replication. The subsequent probability of viral rebound was low.
    • 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; Quillet, C; Fontanet, A; Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France. (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 High Early Mortality in Patients on Antiretroviral Treatment in a Rural District of Malawi.

      Zachariah, R; Fitzgerald, M; Massaquoi, M; Pasulani, O; Arnould, L; Makombe, S D; Harries, A D; Medecins sans Frontieres, Operational Research, Brussels Operational Center, Belgium. zachariah@internet.lu (2006-11-28)
      OBJECTIVES: Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. DESIGN AND SETTING: A cross-sectional analytical study set in Thyolo district, Malawi. METHODS: Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. RESULTS: A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P
    • Safety of efavirenz in first-trimester of pregnancy: a systematic review and meta-analysis of outcomes from observational cohorts.

      Ford, Nathan; Mofenson, Lynne; Kranzer, Katharina; Medu, Lanre; Frigati, Lisa; Mills, Edward J; Calmy, Alexandra; Médecins Sans Frontières, South Africa Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa cPediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA dLondon School of Hygiene and Tropical Medicine, London, UK eFaculty of Health Sciences, Simon Fraser University, Vancouver, Canada fRed Cross Children's hospital, Cape Town, South Africa gFaculty of Health Sciences, University of Ottawa, Canada hGeneva University Hospital, HIV Unit, Service of Infectious Diseases, Geneva, Switzerland. (2010-05-14)
      INTRODUCTION
    • Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis

      Ford, Nathan; Calmy, Alexandra; Mofenson, Lynne; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; Médecins Sans Frontières, Geneva, Switzerland; Geneva University Hospital, HIV Unit, Service of Infectious Diseases, Geneva, Switzerland; Pediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA (Lippincott Williams & Wilkins, 2011-11-28)
      Evidence of the risk of birth defects with efavirenz use is limited. We updated a meta-analysis of birth defects in infants with first trimester efavirenz exposure up to July 2011. In 21 studies, there were 39 defects among live births in 1437 women receiving first trimester efavirenz [2.0%, 95% confidence interval (CI) 0.82-3.18]. The relative risk of defects comparing women on efavirenz-based (1290 live births) and nonefavirenz-based regimens (8122 live births) was 0.85 (95% CI 0.61-1.20). One neural tube defect was observed (myelomeningocele), giving an incidence of 0.07% (95% CI 0.002-0.39).