• Paediatric HIV care in sub-Saharan Africa: clinical presentation and 2-year outcomes stratified by age group

      Ben-Farhat, Jihane; Gale, Marianne; Szumilin, Elisabeth; Balkan, Suna; Poulet, Elisabeth; Pujades-Rodríguez, Mar (John Wiley & Sons Ltd, 2013-09)
      To examine age differences in mortality and programme attrition amongst paediatric patients treated in four African HIV programmes.
    • Paediatric HIV testing beyond the context of prevention of mother-to-child transmission: a systematic review and meta-analysis.

      Cohn, Jennifer; Whitehouse, Katherine; Tuttle, Julia; Lueck, Kristin; Tran, Trang (2016-10)
      Many HIV-positive children in low-income and middle-income countries remain undiagnosed. Although HIV testing in children at health facilities is recommended by WHO, it is not well implemented. This systematic review and meta-analysis examines the case-finding benefit of HIV screening in children aged 0-5 years in low-income and middle-income countries.
    • Paediatric HIV Treatment Failure: A Silent Epidemic

      Bernheimer, Jonathan M; Patten, Gem; Makeleni, Thembisa; Mantangana, Nompumelelo; Dumile, Nombasa; Goemaere, Eric; Cox, Vivian (International AIDS Society, 2015-07-23)
      Paediatric antiretroviral treatment (ART) failure is an under-recognized issue that receives inadequate attention in the field of paediatrics and within HIV treatment programmes. With paediatric ART failure rates ranging from 19.3% to over 32% in resource limited settings, a comprehensive evaluation of the causes of failure along with approaches to address barriers to treatment adherence are urgently needed. In partnership with the local Department of Health, a pilot programme has been established by Medecins Sans Frontieres (MSF) in Khayelitsha, South Africa, to identify and support paediatric HIV patients with high viral loads and potential treatment failure. Through detailed clinical and psychosocial evaluations and adherence support with an innovative counselling model, treatment barriers are identified and addressed. Demographic and clinical characteristics from the cohort show a delayed median start date for ART, prolonged viraemia including a large number of patients who have never achieved viral load (VL) suppression, a low rate of regimen changes despite failure, and a high percentage of pre-adolescent and adolescent patients who have not gone through the disclosure process. Stemming this epidemic of paediatric treatment failure requires programmatic responses to high viral loads in children, starting with improved "case finding" of previously undiagnosed HIV-infected children and adolescents. Viral load testing needs to be prioritized over CD4 count monitoring, and flagging systems to identify high VL results should be developed in clinics. Clinicians must understand that successful treatment begins with good adherence, and that simple adherence support strategies can often dramatically improve adherence. Moreover, appropriate adherence counselling should begin not when the child fails to respond to treatment. Establishing good adherence from the beginning of treatment, and supporting ongoing adherence during the milestones in these children's lives is key to sustaining treatment success in this vulnerable HIV-infected patient population.
    • The Partec CyFlow Counter could provide an option for CD4+ T-cell monitoring in the context of scaling-up antiretroviral treatment at the district level in Malawi.

      Fryland, M; Chaillet, P; Zachariah, R; Barnaba, A; Bonte, L; Andereassen, R; Charrondière, S; Teck, R; Didakus, O; Médecins sans Frontières-Luxembourg, Thyolo District, Malawi. (Elsevier, 2006-10)
      A study was conducted in rural Malawi to verify (a) whether the Partec CyFlow Counter((R)) for CD4+ T-cell lymphocyte counting in HIV-positive individuals could be introduced into a district hospital laboratory and (b) whether it would produce CD4 counts of acceptable quality. CD4+ cell counting was performed using the Partec CyFlow Counter and the results were compared with a reference method (FACsCount). A total of 311 blood samples were analysed and the correlation coefficient for the CyFlow Counter was 0.92 (95% CI 0.89-0.95). Mean CD4 counts using the Partec and the reference methods were 308.2 cells/microl and 316.9 cells/microl, respectively. The mean difference in CD4 count values was -8.68 cells/microl (95% CI -18.8 to 1.4). Mean intra-run variation was -6.84 cells/microl (95% CI -12.9 to 0.79). In the district laboratory setting, the instrument could accommodate up to 75 blood samples per technician per day. After being trained, local laboratory staff found the CyFlow Counter procedures simple to run and the instrument easy to manipulate. The Partec CyFlow Counter produces sufficiently reliable results and the instrument appears robust under field conditions. It could provide a new option for introducing routine CD4+ cell monitoring at the district level in the context of scaling-up antiretroviral therapy in Malawi.
    • Patient and health-care worker experiences of an HIV viral load intervention using SMS: A qualitative study.

      Venables, E; Ndlovu, Z; Munyaradzi, D; Martinez-Perez, G; Mbofana, E; Nyika, P; Chidawanyika, H; Bygrave, H; Garone, D (Public Library of Science, 2019-04-11)
      Mobile Health or mHealth interventions, including Short Message Service (SMS), can help increase access to care, enhance the efficiency of health service delivery and improve diagnosis and treatment for HIV. Text messaging, or SMS, allows for the low cost transmission of information, and has been used to send appointment reminders, information about HIV counselling and treatment, messages to encourage adherence and information on nutrition and side-effects. HIV Viral Load (VL) monitoring is recommended by the WHO and has been progressively adopted in many settings. In Zimbabwe, implementation of VL is routine and has been rolled out with support of Médecins Sans Frontières (MSF) since 2012. An SMS intervention to assist with the management of VL results was introduced in two rural districts of Zimbabwe. After completion of the HIV VL testing at the National Microbiology Reference Laboratory in Harare, results were sent to health facilities via SMS. Consenting patients were also sent an SMS informing them that their viral load results were ready for collection at their nearest health facilities. No actual VL results were sent to patients. A qualitative study was conducted in seven health-care facilities using in-depth interviews (n = 32) and focus group discussions (n = 5) to explore patient and health-care worker experiences of the SMS intervention. Purposive sampling was used to select participants to ensure that male and female patients, as well as those with differing VL results and who lived differing distances from the clinics were included. Data were transcribed, translated from Shona into English, coded and thematically analysed using NVivo software. The VL SMS intervention was considered acceptable to patients and health-care workers despite some challenges in implementation. The intervention was perceived by health-care workers as improving adherence and well-being of patients as well as improving the management of VL results at health facilities. However, there were some concerns from participants about the intervention, including challenges in understanding the purpose and language of the messages and patients coming to their health facility unnecessarily. Health-care workers were more concerned than patients about unintentional HIV disclosure relating to the content of the messages or phone-sharing. This was an innovative intervention in Zimbabwe, in which SMS was used to send VL results to health-care facilities, and notifications of the availability of VL results to patients. Interventions such as this have the potential to reduce unnecessary clinic visits and ensure patients with high VL results receive timely support, but they need to be properly explained, alongside routine counselling, for patients to fully benefit. The findings of this study also have potential policy implications, as if implemented well, such an SMS intervention has the potential to help patients adopt a more active role in the self-management of their HIV disease, become more aware of the importance of adherence and VL monitoring and seek follow-up at clinics when results are high.
    • Patient experiences of ART adherence clubs in Khayelitsha and Gugulethu, Cape Town, South Africa: A qualitative study.

      Venables, E; Towriss, C; Rini, Z; Nxiba, X; Cassidy, T; Tutu, S; Grimsrud, A; Myer, L; Wilkinson, L (Public Library of Science, 2019-06-20)
      BACKGROUND: Globally, 37 million people are in need of lifelong antiretroviral treatment (ART). With the continual increase in the number of people living with HIV starting ART and the need for life-long retention and adherence, increasing attention is being paid to differentiated service delivery (DSD), such as adherence clubs. Adherence clubs are groups of 25-30 stable ART patients who meet five times per year at their clinic or a community location and are facilitated by a lay health-care worker who distributes pre-packed ART. This qualitative study explores patient experiences of clubs in two sites in Cape Town, South Africa. METHODS: A total of 144 participants took part in 11 focus group discussions (FGDs) and 56 in-depth interviews in the informal settlements of Khayelitsha and Gugulethu in Cape Town, South Africa. Participants included current club members, stable patients who had never joined a club and club members referred back to clinician-led facility-based standard care. FGDs and interviews were conducted in isiXhosa, translated and transcribed into English, entered into NVivo, coded and thematically analysed. RESULTS: The main themes were 1) understanding and knowledge of clubs; 2) understanding of and barriers to enrolment; 3) perceived benefits and 4) perceived disadvantages of the clubs. Participants viewed membership as an achievement and considered returning to clinician-led care a 'failure'. Moving between clubs and the clinic created frustration and broke down trust in the health-care system. CONCLUSIONS: Adherence clubs were appreciated by patients, particularly time-saving in relation to flexible ART collection. Improved patient understanding of enrolment processes, eligibility and referral criteria and the role of clinical oversight is essential for building relationships with health-care workers and trust in the health-care system.
    • Patient needs and point-of-care requirements for HIV load testing in resource-limited settings

      Usdin, Martine; Guillerm, Martine; Calmy, Alexandra; Medecins Sans Frontieres Access Campaign, Paris, France; University of Liverpool School of Public Health, Liverpool, United Kingdom; Department of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland (2010-04-15)
      Medecins Sans Frontieres (MSF) is an international, independent medical nongovernmental organization. One way in which MSF acts to improve patient care is to assist in the identification and development of adapted and appropriate tools for use in resource-limited settings. One strategy to achieve this goal is through active collaborations with scientists and developers, to make some of the field needs known and to help define the medical strategy behind the implementation of new diagnostic tests. Tests used in the field need to be effective in often extreme conditions and must also deliver high-quality, reliable results that can be used in the local context. In this article, we discuss some patient and health care provider needs for human immunodeficiency virus (HIV) load measurement in resource-limited settings. This is just one of the areas in which effective, quality tools are desperately needed, not only by MSF and other international nongovernmental organizations, but also by many other health service providers. We hope that, by clearly defining the needs of patients in MSF clinics-as well as we can assess this-and by explaining why these tools are needed, how they should perform, and how their results can be integrated into a program, we will encourage the development of such tools and hasten their implementation in areas where they are so urgently needed.
    • Patient retention and attrition on antiretroviral treatment at district level in rural Malawi.

      Massaquoi, M; Zachariah, R; Manzi, M; Pasulani, O; Misindi, D; Mwagomba, B; Bauernfeind, A; Harries, A D; Médecins Sans Frontières, Thyolo District, Thyolo, Malawi. (Published by Elsevier, 2009-06)
      We report on rates of patient retention and attrition in the context of scaling-up antiretroviral treatment (ART) within a district hospital and its primary health centres in rural Malawi. 'Retention' was defined as being alive and on ART or transferred out, whereas 'attrition' was defined as died, lost to follow-up or stopped treatment. A total of 4074 patients were followed-up for 1803 person-years: 2904 were at the hospital and 1170 at health centres. Approximately 85% of patients were retained in care, both at hospital and health centres, with a retention rate per 100 person-years of 185 and 211, respectively [adjusted hazard ratio (HR) 1.18, 95% CI 1.10-1.28, P=0.001). Attrition rates per 100 person-years were similar: 33 and 36, respectively (adjusted HR 1.17, 95% CI 0.97-1.4, P=0.1). At health centres the incidence of loss to follow-up was significantly lower than at the hospital (adjusted HR 0.24, P<0.001, risk reduction 77%), but the rate of reported deaths was higher at health centres (adjusted HR 2.2, 95% CI 1.76-2.72, P<0.001). As Malawi continues to extend the coverage (and equity) of ART, including in rural areas, attention is needed to reduce losses to follow-up at hospital level and reduce mortality at primary care level.
    • 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; et al. (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; et al. (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.
    • Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi.

      Nicholas, S; Poulet, E; Wolters, L; Wapling, J; Rakesh, A; Amoros, I; Szumilin, E; Gueguen, M; Schramm, B (John Wiley & Sons, 2019-08-01)
      INTRODUCTION: Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi. METHODS: We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. RESULTS AND DISCUSSION: Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed. CONCLUSIONS: Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.
    • 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; et al. (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).