• Payment for antiretroviral drugs is associated with a higher rate of patients lost to follow-up than those offered free-of-charge therapy in Nairobi, Kenya.

      Zachariah, R; Van Engelgem, I; Massaquoi, M; Kocholla, L; Manzi, M; Suleh, A; Philips, M; Borgdorff, M; Médecins Sans Frontières - Brussels, Medical Department (Operational Research), 68 Rue de Gasperich, L-1617, Luxembourg. (Elsevier, 2008-03)
      This retrospective analysis of routine programme data from Mbagathi District Hospital, Nairobi, Kenya shows the difference in rates of loss to follow-up between a cohort that paid 500 shillings/month (approximately US$7) for antiretroviral drugs (ART) and one that received medication free of charge. A total of 435 individuals (mean age 31.5 years, 65% female) was followed-up for 146 person-years: 265 were in the 'payment' cohort and 170 in the 'free' cohort. The incidence rate for loss to follow-up per 100 person-years was 47.2 and 20.5, respectively (adjusted hazard ratio 2.27, 95% CI 1.21-4.24, P=0.01). Overall risk reduction attributed to offering ART free of charge was 56.6% (95% CI 20.0-76.5). Five patients diluted their ART regimen to one tablet (instead of two tablets) twice daily in order to reduce the monthly cost of medication by half. All these patients were from the payment cohort. Payment for ART is associated with a significantly higher rate of loss to follow-up, as some patients might be unable to sustain payment over time. In resource-limited settings, ART should be offered free of charge in order to promote treatment compliance and prevent the emergence of drug resistance.
    • Pediatric Access and Continuity of HIV Care Before the Start of Antiretroviral Therapy in Sub-Saharan Africa

      Bastard, M; Poulet, E; Nicolay, N; Szumilin, E; Balkan, S; Pujades-Rodriguez, M (Wolters Kluwer, 2016-09-01)
      The number of HIV-infected children starting antiretroviral treatment (ART) has increased in resource-limited settings during the past decades. However, there are still few published data on the characteristics of pediatric patients at program enrolment and on the dynamics of dropping out before the start of ART.
    • Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa

      Barnett, W; Patten, G; Kerschberger, B; Conradie, K; Garone, DB; Van Cutsem, G; Colvin, CJ (Health and Medical Publishing Group, 2013-12)
    • Performance of cepheid GeneXpert HIV-1 viral load plasma assay to accurately detect treatment failure: a clinical meta-analysis

      Sacks, JA; Fong, Y; Gonzalez, MP; Andreotti, M; Baliga, S; Garrett, N; Jordan, J; Karita, E; Kulkarni, S; Mor, O; Mosha, F; Ndlovu, Z; Plantier, JC; Saravanan, S; Scott, L; Peter, T; Doherty, M; Alexander, H; Vojnov, L (Wolters Kluwer Health / Lippincott Williams & Wilkins, 2019-07-02)
      Background: Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies. Methods: Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml). Results: Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02–0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2–96.3) and specificity was 80.56% (95% CI: 64.6–90.4). Conclusion: The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.
    • Performance of FASTPlaqueTB and a modified protocol in a high HIV prevalence community in South Africa.

      Trollip, A P; Albert, H; Mole, R; Marshall, T; van Cutsem, G; Coetzee, D; Biotec Laboratories South Africa Ltd, Cape Town, South Africa. andre.trollip@bioteclabs.co.za (2009-06)
      Modifications in the FASTPlaqueTB test protocol have resulted in an increase in the analytical limits of detection. This study investigated whether the performance of a modified prototype was able to increase the detection of smear-negative, culture-positive sputum samples as compared to the first generation FASTPlaqueTB test. Modifications to the FASTPlaqueTB did result in increased detection of smear-negative samples, but this was associated with a decrease in the specificity of the test. Before the FASTPlaqueTB can be considered as a viable replacement for smear microscopy and culture for the identification of tuberculosis, further work is required to resolve the performance issues identified in this study.
    • Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial).

      Borand, Laurence; Madec, Yoann; Laureillard, Didier; Chou, Monidarin; Marcy, Olivier; Pheng, Phearavin; Prak, Narom; Kim, Chindamony; Lak, Khemarin Kim; Hak, Chanroeun; Dim, Bunnet; Nerrienet, Eric; Fontanet, Arnaud; Sok, Thim; Goldfeld, Anne E; Blanc, François-Xavier; Taburet, Anne-Marie (Public Library of Science, 2014)
      To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.
    • Pooled HIV-1 Viral Load Testing Using Dried Blood Spots to Reduce the Cost of Monitoring Antiretroviral Treatment in a Resource-Limited Setting

      Pannus, Pieter; Fajardo, Emmanuel; Metcalf, Carol; Coulborn, Rebecca M; Durán, Laura T; Bygrave, Helen; Ellman, Tom; Garone, Daniela; Murowa, Michael; Mwenda, Reuben; Reid, Tony; Preiser, Wolfgang; *Médecins Sans Frontières, Southern Africa Medical Unit, Cape Town, South Africa; †Médecins Sans Frontières, Thyolo, Malawi; ‡Ministry of Health, Health Technical Support Services, Diagnostics, District Management Office, Thyolo, Malawi; §Ministry of Health, Lilongwe, Malawi; ‖Médecins Sans Frontières, Operational Research Unit, Brussels, Belgium; and ¶Division of Medical Virology, Stellenbosch University, and National Health Laboratory Service, Tygerberg, South Africa. (Lippincott Williams & Wilkins, 2013-10-01)
      : Rollout of routine HIV-1 viral load monitoring is hampered by high costs and logistical difficulties associated with sample collection and transport. New strategies are needed to overcome these constraints. Dried blood spots from finger pricks have been shown to be more practical than the use of plasma specimens, and pooling strategies using plasma specimens have been demonstrated to be an efficient method to reduce costs. This study found that combination of finger-prick dried blood spots and a pooling strategy is a feasible and efficient option to reduce costs, while maintaining accuracy in the context of a district hospital in Malawi.
    • Population Differences in Death Rates in HIV-Positive Patients with Tuberculosis.

      Ciglenecki, I; Glynn, J R; Mwinga, A; Ngwira, B; Zumla, A; Fine, P E M; Nunn, A; Médecins Sans Frontières, Geneva, Switzerland. iza_ciglenecki@yahoo.com (International Union Against TB and Lung Disease, 2007-10)
      SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality.
    • Population-level HIV incidence estimates using a combination of synthetic cohort and recency biomarker approaches in KwaZulu-Natal, South Africa

      Grebe, E; Welte, A; Johnson, LF; van Cutsem, G; Puren, A; Ellman, T; Etard, JF; Huerga, H (Public Library of Science, 2018-09-13)
      There is a notable absence of consensus on how to generate estimates of population-level incidence. Incidence is a considerably more sensitive indicator of epidemiological trends than prevalence, but is harder to estimate. We used a novel hybrid method to estimate HIV incidence by age and sex in a rural district of KwaZulu-Natal, South Africa.
    • Positive spill-over effects of ART scale up on wider health systems development: evidence from Ethiopia and Malawi

      Rasschaert, Freya; Pirard, Marjan; Philips, Mit P; Atun, Rifat; Wouters, Edwin; Assefa, Yibeltal; Criel, Bart; Schouten, Erik J; Van Damme, Wim (2011)
    • Potential Impact of Multiple Interventions on HIV Incidence in a Hyperendemic Region in Western Kenya: a Modelling Study

      Blaizot, S; Maman, D; Riche, B; Mukui, I; Kirubi, B; Ecochard, R; Etard, JF (BioMed Central, 2016-04-29)
      Multiple prevention interventions, including early antiretroviral therapy initiation, may reduce HIV incidence in hyperendemic settings. Our aim was to predict the short-term impact of various single and combined interventions on HIV spreading in the adult population of Ndhiwa subcounty (Nyanza Province, Kenya).
    • Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

      Bedell, RA; van Lettow, M; Meaney, C; Corbett, EL; Chan, AK; Heyderman, RS; Anderson, ST; Akesson, A; Kumwenda, M; Zachariah, R; Harries, AD; Ramsay, AR (Wiley-Blackwell, 2018-01-01)
      BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). METHODS: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. RESULTS: Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. CONCLUSION: High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.
    • Predictors of Raised Viral Load during Antiretroviral Therapy in Patients with and without Prior Antiretroviral Use: A Cross-Sectional Study

      Greig, Jane E.; du Cros, Philipp A; Mills, Clair; Ugwoeruchukwu, Wilfred; Etsetowaghan, Andrew; Grillo, Adetola; Tayo-Adetoro, Adetoro; Omiyale, Kunle; Spelman, Tim; O'Brien, Daniel P.; Manson Unit, Médecins Sans Frontières, London, United Kingdom. jane.greig@london.msf.org (PLoS, 2013-08-14)
      In Lagos, Nigeria, Médecins Sans Frontières (MSF) and the Ministry of Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based clinic. We performed a cross-sectional study to compare factors associated with raised viral load between patients with ("experienced") and without ("naïve") prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also examined factors influencing ARV adherence in experienced patients prior to clinic entry.
    • Preferred antiretroviral drugs for the next decade of scale up

      Andrieux-Meyer, Isabelle; Calmy, Alexandra; Cahn, Pedro; Clayden, Polly; Raguin, Gilles; Katlama, Christine; Vitoria, Marco; Levin, Andrew; Lynch, Sharonann; Goemaere, Eric; Ford, Nathan; Médecins Sans Frontières, Geneva, Switzerland. (2012-09-18)
      Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer-term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.
    • Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007)

      Micol, Romain; Buchy, Philippe; Guerrier, Gilles; Duong, Veasna; Ferradini, Laurent; Dousset, Jean-Philippe; Guerin, Philippe J; Balkan, Suna; Galimand, Julie; Chanroeun, Hak; Lortholary, Olivier; Rouzioux, Christine; Fontanet, Arnaud; Leruez-Ville, Marianne; Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France; Laboratoire de Virologie, Universite Rene Descartes, Hopital Necker-Enfants Malades, Paris, France; Unite de virologie, Institut Pasteur du Cambodge, Phnom Penh, Cambodia; Medecins Sans Frontieres, Hopital Prea Bath Norodom Sihanouk, Phnom Penh, Cambodia; Medecins Du Monde, Hopital Kosamak, Phnom Penh, Cambodia; Epicentre, Paris, France; Medecins Sans Frontieres, Paris, France; Service des Maladies Infectieuses et Tropicales, Hopital Calmette, Phnom Penh, Cambodia; Universite Rene Descartes, Service des Maladies Infectieuses et Tropicales, Centre d’Infectiologie Necker–Pasteur, Hopital Necker–Enfants Malades, Paris, France (2009-08-01)
      BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality.
    • Preventing HIV-1: lessons from Mwanza and Rakai.

      Matthys, F; Boelaert, M (Elsevier, 1999-05-01)
    • The prevention of mother-to-child HIV transmission programme and infant feeding practices.

      Hilderbrand, K; Goemaere, E; Coetzee, D; Infectious Diseases and HIV/AIDS Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town. (2003-10)
      Since the first cases of HIV transmission through breast-feeding were documented, a fierce debate has raged on appropriate guidelines for infant feeding in resource-poor settings. A major problem is determining when it is safe and feasible to formula-feed, as breast-milk protects against other diseases. A cross-sectional survey of 113 women attending the programme for the prevention of mother-to-child transmission in Khayelitsha, Cape Town, was conducted. Over 95% of women on the programme formula-fed their infants and did not breast-feed at all. Seventy per cent of women said that their infant had never had diarrhoea, and only 3% of children had had two episodes of diarrhoea. Focus groups identified the main reasons for not breast-feeding given by women to their families and those around them. Formula feeding is safe and feasible in an urban environment where sufficient potable water is available.
    • Prevention of mother-to-child transmission of HIV and the health-related Millennium Development Goals: time for a public health approach.

      Schouten, Erik J; Jahn, Andreas; Midiani, Dalitso; Makombe, Simon D; Mnthambala, Austin; Chirwa, Zengani; Harries, Anthony D; van Oosterhout, Joep J; Meguid, Tarek; Ben-Smith, Anne; Zachariah, Rony; Lynen, Lutgarde; Zolfo, Maria; Van Damme, Wim; Gilks, Charles F; Atun, Rifat; Shawa, Mary; Chimbwandira, Frank; Department of HIV and AIDS, Ministry of Health, Lilongwe, Malawi. eschouten@msh.org (2011-07-16)
    • Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings

      Spaar, A; Graber, C; Dabis, F; Coutsoudis, A; Bachmann, L; McIntyre, J; Schechter, M; Prozesky, H W; Tuboi, S; Dickinson, D; Kumarasamy, N; Pujdades-Rodriquez, M; Sprinz, E; Schilthuis, H J; Cahn, P; Low, N; Egger, M; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; Horten Centre for Patient-oriented Research and Knowledge Transfer, University Hospital of Zurich, Zurich, Switzerland; Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED), Université Victor Segalen, Bordeaux, France; Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa; Perinatal HIV Research Unit (PHRU), Soweto, South Africa; Rio HIV Cohort, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Tygerberg Academic Hospital, Cape Town, South Africa; Independent Surgery, Gaborone, Botswana; Y R Gaitonde Centre for AIDS Research and Education (YRG Care), Chennai, India; Epicentre, Paris, France; South Brazil HIV Cohort (SOBRHIV), Hospital de Clinicas, Porto Alegre, Brazil; Heineken Medical Services, Amsterdam, The Netherlands; Fundación Huesped, Buenos Aires, Argentina (2010-05-13)
      Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.
    • Programmatic outcomes and impact of rapid public sector antiretroviral therapy expansion in adults prior to introduction of the WHO treat-all approach in rural Eswatini.

      Boulle, A; Teck, R; Lukhele, N; Rusch, B; Telnov, A; Mabhena, E; Pasipamire, L; Ciglenecki, I; Schomaker, M; Kerschberger, B (John Wiley & Sons, 2019-04-01)
      To assess long-term antiretroviral therapy (ART) outcomes during rapid HIV programme expansion in the public sector of Eswatini (formerly Swaziland). This is a retrospectively established cohort of HIV-positive adults (≥16 years) who started first-line ART in 25 health facilities in Shiselweni (Eswatini) between 01/2006 and 12/2014. Temporal trends in ART attrition, treatment expansion and ART coverage were described over 9 years. We used flexible parametric survival models to assess the relationship between time to ART attrition and covariates. Of 24 772 ART initiations, 6% (n = 1488) occurred in 2006, vs. 13% (n = 3192) in 2014. Between these years, median CD4 cell count at ART initiation increased (113-265 cells/mm Programmatic outcomes improved during large expansion of the treatment cohort and increased ART coverage. Changes in ART programming may have contributed to better outcomes.