Shabbar Jaffar

London School of Hygiene and Tropical Medicine, Londinium, England, United Kingdom

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Publications (159)1078.2 Total impact

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    ABSTRACT: Mortality in people in Africa with HIV infection starting antiretroviral therapy (ART) is high, particularly in those with advanced disease. We assessed the effect of a short period of community support to supplement clinic-based services combined with serum cryptococcal antigen screening. We did an open-label, randomised controlled trial in six urban clinics in Dar es Salaam, Tanzania, and Lusaka, Zambia. From February, 2012, we enrolled eligible individuals with HIV infection (age ≥18 years, CD4 count of <200 cells per μL, ART naive) and randomly assigned them to either the standard clinic-based care supplemented with community support or standard clinic-based care alone, stratified by country and clinic, in permuted block sizes of ten. Clinic plus community support consisted of screening for serum cryptococcal antigen combined with antifungal therapy for patients testing antigen positive, weekly home visits for the first 4 weeks on ART by lay workers to provide support, and in Tanzania alone, re-screening for tuberculosis at 6-8 weeks after ART initiation. The primary endpoint was all-cause mortality at 12 months, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISCRTN 20410413. Between Feb 9, 2012, and Sept 30, 2013, 1001 patients were randomly assigned to clinic plus community support and 998 to standard care. 89 (9%) of 1001 participants in the clinic plus community support group did not receive their assigned intervention, and 11 (1%) of 998 participants in the standard care group received a home visit or a cryptococcal antigen screen rather than only standard care. At 12 months, 25 (2%) of 1001 participants in the clinic plus community support group and 24 (2%) of 998 participants in the standard care group had been lost to follow-up, and were censored at their last visit for the primary analysis. At 12 months, 134 (13%) of 1001 participants in the clinic plus community support group had died compared with 180 (18%) of 998 in the standard care group. Mortality was 28% (95% CI 10-43) lower in the clinic plus community support group than in standard care group (p=0·004). Screening and pre-emptive treatment for cryptococcal infection combined with a short initial period of adherence support after initiation of ART could substantially reduce mortality in HIV programmes in Africa. European and Developing Countries Clinical Trials Partnership. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet 03/2015; 385(9983). DOI:10.1016/S0140-6736(15)60164-7 · 45.22 Impact Factor
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    ABSTRACT: Despite a recent decline, Zimbabwe still has the fifth highest adult HIV prevalence in the world at 14.7%; 56% of the population are currently living in extreme poverty. Cross-sectional population-based survey of 18-22 year olds, conducted in 30 communities in south-eastern Zimbabwe in 2007. To examine whether the risk of HIV infection among young rural Zimbabwean women is associated with socio-economic position and whether different socio-economic domains, including food sufficiency, might be associated with HIV risk in different ways. Eligible participants completed a structured questionnaire and provided a finger-prick blood sample tested for antibodies to HIV and HSV-2. The relationship between poverty and HIV was explored for three socio-economic domains: ability to afford essential items; asset wealth; food sufficiency. Analyses were performed to examine whether these domains were associated with HIV infection or risk factors for infection among young women, and to explore which factors might mediate the relationship between poverty and HIV. 2593 eligible females participated in the survey and were included in the analyses. Overall HIV prevalence among these young females was 7.7% (95% CI: 6.7-8.7); HSV-2 prevalence was 11.2% (95% CI: 9.9-12.4). Lower socio-economic position was associated with lower educational attainment, earlier marriage, increased risk of depression and anxiety disorders and increased reporting of higher risk sexual behaviours such as earlier sexual debut, more and older sexual partners and transactional sex. Young women reporting insufficient food were at increased risk of HIV infection and HSV-2. This study provides evidence from Zimbabwe that among young poor women, economic need and food insufficiency are associated with the adoption of unsafe behaviours. Targeted structural interventions that aim to tackle social and economic constraints including insufficient food should be developed and evaluated alongside behaviour and biomedical interventions, as a component of HIV prevention programming and policy.
    PLoS ONE 01/2015; 10(1):e0115290. DOI:10.1371/journal.pone.0115290 · 3.23 Impact Factor
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    ABSTRACT: Objectives In response to the lack of evidence-based guidance for how to continue scaling up antiretroviral therapy (ART) in ways that make optimal use of limited resources, to assess comparative studies of ART service delivery models implemented in sub-Saharan Africa.MethodsA systematic literature search and analysis of studies that compared two or more methods of ART service delivery using either CD4 count or viral load as a primary outcome.ResultsMost studies identified in this review were small and non-randomised, with low statistical power. Four of the 30 articles identified by this review conclude that nurse management of ART compares favourably to physician management. Seven provide evidence of the viability of managing ART at lower levels within the health system, and one indicates that vertical and integrated ART programmes can achieve similar outcomes. Five articles show that community/home-based ART management can be as effective as facility-based ART management. Five of seven articles investigating community support link it to better clinical outcomes. The results of four studies suggest that directly observed therapy may not be an important component of ART programmes.Conclusions Given that the scale-up of antiretroviral therapy represents the most sweeping change in healthcare delivery in sub-Saharan Africa in recent years, it is surprising to not find more evidence from comparative studies to inform implementation strategies. The studies reported on a wide range of service delivery models, making it difficult to draw conclusions about some models. The strongest evidence was related to the feasibility of decentralisation and task-shifting, both of which appear to be effective strategies.
    Tropical Medicine & International Health 07/2014; 19(10). DOI:10.1111/tmi.12366 · 2.33 Impact Factor
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    ABSTRACT: African health services have shortages of clinical staff. We showed previously, in a cluster-randomized trial, that a home-based strategy using trained lay-workers is as effective as a clinic-based strategy. It is not known whether home-based care is suitable for patients with advanced HIV disease. The trial was conducted in Jinja, Uganda. One thousand, four hundred and fifty-three adults initiating ART between February 2005 and January 2009 were randomized to receive either home-based care or routine clinic-based care, and followed up for about 3 years. Trained lay workers, supervised by clinical staff based in a clinic, delivered the home-based care. In this sub-analysis, we compared survival between the two strategies for those who presented with CD4 cell count less than 50 cells/μl and those who presented with higher CD4 cell counts. We used Kaplan-Meier methods and Poisson regression. Four hundred and forty four of 1453 (31%) participants had baseline CD4 cell count less than 50 cells/μl. Overall, 110 (25%) deaths occurred among participants with baseline CD4 cell count less than 50 cells/μl and 87 (9%) in those with higher CD4 cell count. Among participants with CD4 cell count less than 50 cells/μl, mortality rates were similar for the home and facility-based arms; adjusted mortality rate ratio 0.80 [95% confidence interval (CI) 0.53-1.18] compared with 1.22 (95% CI 0.78-1.89) for those who presented with higher CD4 cell count. HIV home-based care, with lay workers playing a major role in the delivery of care including providing monthly adherence support, leads to similar survival rates as clinic-based care even among patients who present with very low CD4 cell count. This emphasises the critical role of adherence to antiretroviral therapy.
    AIDS (London, England) 02/2014; 28(4):569-76. DOI:10.1097/QAD.0000000000000056 · 5.55 Impact Factor
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    ABSTRACT: Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0–1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4–11.1), high peripheral white blood cell count (>10 × 109 cells/L; OR, 8.7; 95% CI, 2.5–30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). Conclusions. CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.
    Clinical Infectious Diseases 12/2013; 58(5). DOI:10.1093/cid/cit794 · 8.89 Impact Factor
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    Tropical Medicine & International Health 11/2013; 19(1). DOI:10.1111/tmi.12230 · 2.33 Impact Factor
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    ABSTRACT: We report on the adherence experience of a group of people living with HIV on ART over six years in Uganda. Between 2005 and 2009, we followed up 41 participants who were also part of a clinical trial comparing home and facility based delivery of ART in Jinja, eastern Uganda. We conducted qualitative in-depth interviews at enrolment, 3, 6, 18 and 30 months to capture experiences with adherence over time. In 2011 we returned to these participants to find out how they were fairing with long term adherence. We managed to retrace 24 participants and interviewed them about their experience. We thematically analysed the data and compared findings over time. Initially there were few barriers to adherence and many followed the adherence guidance closely. By year six, relaxation of these rules was noticeable although self-reported adherence continued to be high. Alcohol consumption was more common than before. Some relatives of the participants who had died claimed that some deaths were a result of alcohol. While participants reported that ART had allowed them to reclaim independence and return to work the changes in work and social routines created new challenges for adherence. Side effects like lipodystrophy were not only causing some stigma but for some tested their faith in the drugs. Many participants reported resumption of sexual lives but apart from those who selected same status partners, disclosure to new partners was minimal. Good adherence practice to ART wanes over the long-term, and people who may have disclosed at initiation find it difficult to do so to new partners once they are healthy. Further adherence interventions and support with disclosure over the course of therapy may need to be considered. (Words: 283).
    PLoS ONE 10/2013; 8(10):e78243. DOI:10.1371/journal.pone.0078243 · 3.23 Impact Factor
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    ABSTRACT: Stigma is a barrier to HIV prevention and treatment. There is a limited understanding of the types of stigma facing people living with HIV (PLHIV) on antiretroviral therapy (ART). We describe the stigma trajectories of PLHIV over a 5-year period from the time they started ART. Longitudinal qualitative in-depth interviews were conducted with 41 members of The AIDS Support Organisation (TASO) from 2005 to 2008 in Jinja, Uganda, who were part of a pragmatic cluster-randomised trial comparing two different modes of ART delivery (facility and home). Participants were stratified by gender, ART delivery arm and HIV stage (early or advanced) and interviewed at enrolment on to ART and then after 3, 6, 18 and 30 months. Interviews focused on stigma and ART experiences. In 2011, follow-up interviews were conducted with 24 of the participants who could be traced. Transcribed texts were translated, coded and analyzed thematically. Stigma was reported to be very high prior to starting ART, explained by visible signs of long-term illnesses and experiences of discrimination and abuse. Early coping strategies included: withdrawal from public life, leaving work due to ill health and moving in with relatives. Starting ART led to a steady decline in stigma and allowed the participants to take control of their illness and manage their social lives. Better health led to resumption of work and having sex but led to reduced disclosure to employers, colleagues and new sexual partners. Some participants mentioned sero-sorting in order to avoid questions around HIV sero-status. A rise in stigma levels during the 18 and 30 month interviews may be correlated with decreased disclosure. By 2011, ART-related stigma was even more pronounced particularly among those who had started new sexual relationships, gained employment and those who had bodily signs from ART side-effects. This study has shown that while ART comes with health benefits which help individuals to get rid of previously stigmatising visible signs, an increase in stigma may be noticed after about five years on ART, leading to reduced disclosure. ART adherence counselling should reflect changing causes and manifestations of stigma over time.
    BMC Public Health 09/2013; 13(1):804. DOI:10.1186/1471-2458-13-804 · 2.26 Impact Factor
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    S Jaffar · A Amberbir · N Kayuni · C Musicha · M Nyirenda
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    ABSTRACT: The burden of non-communicable diseases in Africa is rising rapidly and implementation of evidence-based control strategies is needed urgently. Testing people for hypertension and diabetes will be an important component in the fight against these diseases, as voluntary counselling and testing was for HIV-infection. We discuss the below the areas where we believe evidence is needed to inform policy.
    Tropical Medicine & International Health 09/2013; 18(11). DOI:10.1111/tmi.12180 · 2.33 Impact Factor
  • Tropical Medicine & International Health 09/2013; 18:18-18. · 2.33 Impact Factor
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    ABSTRACT: Tout d'abord, nous sommes en désaccord avec le traitement de la recherche opérationnelle différemment de la recherche “académique” et comme nécessitant des normes et une apologie distinctes. Nous pensons que le débat serait plus clair si, au lieu des termes recherche «académique» et «opérationnelle», on parle plutôt de recherche dans des «tours d'ivoires» et dans le «monde réel» respectivement. Deuxièmement, même si nous partageons la préoccupation de Zachariah et al. de faire participer les gestionnaires de programmes, les décideurs et autres intervenants dans le processus de recherche, nous voyons la paternité d'auteur scientifique comme une incitation, mais pas seulement pour encourager les «l'octroi de permission». Nous voyons cela comme motivant un esprit de recherche, la promotion de la recherche et la participation active à la recherche, afin d'informer les prises de décisions dans le domaine de la médecine tropicale et de la santé internationale. En primer lugar, estamos en desacuerdo con el tratamiento de la investigación de operaciones como algo diferente a la investigación “académica “ y como algo que requiere de diferentes estándares y de una apología distintiva. Pensamos que la discusión sería más clara si en vez de investigación “académica” y “operativa”, nos refiriésemos a investigación de “torre de marfil” y de “mundo real” respectivamente. En segundo lugar, mientras compartimos la preocupación de Zachariah et al. de involucrar a los gestores de programa, a los políticos y a otros profesionales dentro del proceso de investigación, vemos la autoría científica como un incentivo, pero no solo para estimular la “concesión de permisos”; lo vemos como algo que motiva el espíritu de búsqueda, la promoción activa de y la participación en la investigación, para sustentar la toma de decisiones en el campo de la medicina tropical y de la salud internacional.
    Tropical Medicine & International Health 08/2013; 18(10). DOI:10.1111/tmi.12174 · 2.33 Impact Factor
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    ABSTRACT: In almost all countries, development of health systems that are responsive to the challenge of prevention and treatment of non-communicable diseases (NCDs) is a priority. NCDs consist of a vast group of conditions, but in terms of premature mortality, emphasis has been on cardiovascular disease, cancer, diabetes, and chronic respiratory diseases—diseases that were also the focus of the UN high-level meeting on NCDs, held in 2011. 1In 1990, there were 26·6 million deaths worldwide from NCDs (57·2% ...
    The Lancet 02/2013; 381(9867):690-7. DOI:10.1016/S0140-6736(13)60063-X · 45.22 Impact Factor
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    ABSTRACT: Shah Ebrahim and colleagues argue that more research on non-communicable diseases (NCDs) in both high-income countries and low- and middle-income countries can result in mutual benefits and will help better address the growing burden of NCDs.
    PLoS Medicine 01/2013; 10(1):e1001377. DOI:10.1371/journal.pmed.1001377 · 14.43 Impact Factor
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    ABSTRACT: Cryptococcal meningitis in Africa is associated with up to 70% mortality at 3 months and 500 000 deaths annually. We examined strategies to improve on fluconazole (FLU) monotherapy: addition of flucytosine (5-FC) and/or addition of short-course amphotericin B (AmB). In step 1, previously reported, patients were randomized to receive FLU 1200 mg per day with or without 5-FC 100 mg/kg per day for 14 days. In step 2, 43 patients were similarly randomized, with addition of AmB 1 mg/kg per day for 7 days to both arms. After 2 weeks, patients received FLU monotherapy and were followed to 10 weeks. The primary endpoint was rate of clearance of infection (early fungicidal activity, EFA). Secondary endpoints related to safety and mortality. Forty patients (25% with Glasgow Coma Scale <15) were analyzed. EFA for the triple combination arm was greater than that for AmB-FLU: -0.50 ± 0.15 log CFU/day vs. -0.38 ± 0.19 log colony forming units per day (P=0.03); and greater than that for step 1 with FLU-5-FC (-0.28 ± 0.17) or FLU alone (-0.11 ± 0.09). Combined analysis across steps revealed that addition of 5-FC and AmB had significant, independent additive effects on EFA, with trends toward fewer early deaths with addition of 5-FC (4/41 vs. 11/39, P = 0.05) and fewer deaths overall with addition of AmB (13/39 vs. 20/40, P = 0.1). Addition of 5-FC and short-course AmB to high-dose FLU significantly enhanced EFA and may be associated with favorable trends in survival. Both these strategies should be tested in a larger phase III study.
    AIDS (London, England) 04/2012; 26(11):1363-70. DOI:10.1097/QAD.0b013e328354b419 · 5.55 Impact Factor
  • Bart Van Rompaye · Shabbar Jaffar · Els Goetghebeur
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    ABSTRACT: While epidemiologic and clinical research often aims to analyze predictors of specific endpoints, time-to-the-specific-event analysis can be hampered by problems with cause ascertainment. Under typical assumptions of competing risks analysis (and missing-data settings), we correct the cause-specific proportional hazards analysis when information on the reliability of diagnosis is available. Our method avoids bias in effect estimates at low cost in variance, thus offering a perspective for better-informed decision making. The ratio of different cause-specific hazards can be estimated flexibly for this purpose. It thus complements an all-cause analysis. In a sensitivity analysis, this approach can reveal the likely extent and direction of the bias of a standard cause-specific analysis when the diagnosis is suspect. These 2 uses are illustrated in a randomized vaccine trial and an epidemiologic cohort study, respectively.
    Epidemiology (Cambridge, Mass.) 03/2012; 23(2):194-202. DOI:10.1097/EDE.0b013e3182454cad · 6.20 Impact Factor
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    ABSTRACT: The choice of research method relevant to the evaluation of delivery of a health intervention is not always straightforward. We use the evaluation of HIV and tuberculosis community treatment supporters in promoting adherence to treatment in Africa as a case study to illustrate the pros and cons of operational research and randomised controlled trials. The choice of this intervention for the case study reflects the importance of maximising the benefits of unprecedented efforts to scale-up treatments of these two epidemics. International policy supporting the role of community treatment supporters in tuberculosis is largely based on the findings of operational research studies. This reflects the advantages that operational research is less costly than randomised controlled trials, provides more rapid answers to policy questions, enables standard evaluation of the intervention in ‘real life’ conditions in several diverse settings and has in-built potential to influence policy and practice, because the research is conducted within health programmes. Recent evidence on the role of community treatment supporters in HIV is largely based on randomised trials. This reflects the advantages that randomised trials compared to operational research are more rigorous and generate a more convincing result. Operational research and randomised trials may be viewed as providing complementary findings to inform new policies and practice aimed at improving programme performance and patient outcomes. However, in practice, insufficient funds are likely to be made available for randomised trials to answer all the current research questions on delivery of programme interventions. In deciding on the type of research to evaluate a particular health intervention, dialogue is necessary with policy-makers to weigh up explicitly the trade-offs between research rigour and other factors such as cost, speed of implementation of research and speed of policy uptake and of change in programme practice. Le choix de la méthode de recherche appropriée pour l’évaluation de la délivrance d’une intervention de santé n’est pas toujours simple. Nous utilisons l’évaluation des partisans communautaires du traitement du VIH et la tuberculose pour la promotion de l’adhésion au traitement en Afrique, comme une étude de cas permettant d’illustrer les avantages et les inconvénients de la recherche opérationnelle et des essais contrôlés randomisés. Le choix de cette intervention pour l’étude de cas illustre l’importance de maximiser les avantages des efforts sans précédent pour le déploiement des traitements de ces deux épidémies. La politique internationale soutenant le rôle des partisans communautaires du traitement de la tuberculose est largement basée sur les résultats des études de recherche opérationnelle. Cela reflète les avantages de la recherche opérationnelle qui est moins coûteuse que les essais randomisés contrôlés, fournit plus rapidement des réponses à des questions de politique, permet une évaluation standard de l’intervention dans des conditions de «vie réelle» dans plusieurs contextes divers et englobe le potentiel d’influencer les politiques et les pratiques, puisque la recherche est menée au sein des programmes de santé. Des données récentes sur le rôle des partisans communautaires du traitement en matière de VIH sont largement basées sur des essais randomisés. Cela reflète les avantages que les essais randomisés, par rapport à la recherche opérationnelle sont plus rigoureux et génèrent un résultat plus convaincant, avec une plus grande généralisation des résultats. La recherche opérationnelle et les essais randomisés peuvent être considérés comme fournissant des résultats complémentaires pour informer de nouvelles politiques et pratiques visant à améliorer le rendement du programme et des résultats pour les patients. Cependant, dans la pratique, les fonds insuffisants sont susceptibles d’être mis à disposition des essais randomisés pour répondre à toutes les questions actuelles de recherche sur la délivrance des interventions de programme. En décidant du type de recherche pour évaluer une intervention particulière de santé, le dialogue est nécessaire avec les décideurs afin de peser explicitement sur les arbitrages entre la rigueur de la recherche et d’autres facteurs tels que le coût, la rapidité de l’implémentation de la recherche et la vitesse d’adoption de la politique et des changements dans les pratiques du programme. La elección del método de investigación más relevante para la evaluación de una intervención sanitaria no es siempre una tarea sencilla. Hemos utilizado la evaluación de los supervisores comunitarios del tratamiento para el VIH y la TB, en la promoción de la adherencia al tratamiento en África, como caso de estudio para ilustrar los pros y los contras de la investigación de operaciones y los ensayo aleatorizados y controlados. Escoger esta intervención como caso de estudio refleja la importancia de maximizar los beneficios de esfuerzos sin precedentes para llevar a una mayor escala los tratamientos para estas dos epidemias. Las políticas internacionales que apoyan el papel de los supervisores comunitarios del tratamiento de la TB están en gran parte basadas en hallazgos de estudios de investigación de operaciones. Ello es un reflejo del hecho de que la investigación de operaciones es menos costosa que los ensayos controlados y aleatorizados, da respuestas más rápidas a preguntas sobre políticas, permite la evaluación estándar de la intervención en condiciones de “la vida real” en diferentes emplazamientos, y tiene incorporada el potencial de influenciar tanto la política como la práctica, puesto que la investigación se lleva a cabo dentro de los programas sanitarios. La evidencia más reciente sobre el papel de los supervisores comunitarios del tratamiento del VIH está principalmente basada en ensayos aleatorizados. Ello es reflejo de las ventajas que tienen los ensayos aleatorizados en comparación con la investigación de operaciones, siendo más rigurosos y generando resultados más convincentes, con una mayor generalización de los hallazgos. Se puede considerar que la investigación de operaciones y los ensayos aleatorizados aportan hallazgos complementarios, que sirven para documentar nuevas políticas y prácticas, con el objetivo de mejorar el desempeño de los programas y los resultados para los pacientes. Sin embargo en la práctica, y en ausencia de fondos, estos suelen estar más disponibles para ensayos aleatorizados que respondan a todas las preguntas vigentes sobre la entrega de programas de intervención. A la hora de decidir el tipo de investigación para evaluar una intervención sanitaria en particular, es necesario establecer un diálogo con los políticos para sopesar explícitamente el compromiso entre el rigor de la investigación y otros factores tales como el coste, la rapidez de la implementación de la investigación, y la velocidad de acogida de la política y del cambio en la práctica de los programas.
    Tropical Medicine & International Health 12/2011; 17(3):264-271. DOI:10.1111/j.1365-3156.2011.02920.x · 2.33 Impact Factor
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    ABSTRACT: To define more rapidly effective initial antifungal regimens sustainable in resource-constrained settings. Cohort study in SW Uganda: Thirty HIV-seropositive, antiretroviral therapy-naïve, patients with first episode cryptococcal meningitis were treated with high dose fluconazole (1200 mg/d for 2 weeks, then 800 mg/d until ART started) plus amphotericin B (AmB, 1 mg/kg/d), with routine normal saline and potassium supplementation, for the initial 5 days. Outcome measures were early fungicidal activity (EFA), determined by serial quantitative CSF cultures, safety, and mortality. EFA was -0.30 ± 0.11 log CFU/day calculated over the first 2 weeks of treatment, with no reduction in the rate of clearance between days 5 and 14. There was no grade IV hypokalemia or elevated creatinine, and no grade III or IV anemia or elevation of ALT. AmB or high dose fluconazole were not stopped early in any patient. Mortality was 23% at 2, and 28% at 10 weeks. Short course AmB was associated with rapid clearance of infection and was well-tolerated, suggesting it could be used safely in many centres currently relying on fluconazole monotherapy. Phase III trials are needed in African centres to compare short course with the standard 2-week course of AmB.
    The Journal of infection 11/2011; 64(1):76-81. DOI:10.1016/j.jinf.2011.10.014 · 4.44 Impact Factor
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    ABSTRACT: HIV-associated cryptococcal meningitis is associated with an estimated 600 000 deaths worldwide per year. Current standard initial therapy consists of amphotericin B (AmB) plus flucytosine (5-FC), but 5-FC remains largely unavailable in Asia and Africa. Alternative, more widely available, and/or more effective antifungal combination treatment regimens are urgently needed. Eighty HIV-seropositive, antiretroviral naive patients presenting with cryptococcal meningitis were randomized to 4 treatment arms of 2 weeks duration: group 1, AmB (0.7-1 mg/kg) and 5-FC (25 mg/kg 4 times daily); group 2, AmB (0.7-1 mg/kg) and fluconazole (800 mg daily); group 3, AmB (0.7-1 mg/kg) and fluconazole (600 mg twice daily); and group 4, AmB (0.7-1 mg/kg) and voriconazole (300 mg twice daily). The primary end point was the rate of clearance of infection from the cerebrospinal fluid (CSF) or early fungicidal activity (EFA), as determined by results of serial, quantitative CSF cryptococcal cultures. There were no statistically significant differences in the rate of clearance of cryptococcal colony-forming units (CFU) in CSF samples among the 4 treatment groups; the mean (±standard deviation) EFA for treatment groups 1, 2, 3, and 4 were -0.41 ± 0.22 log CFU/mL CSF/day, -0.38 ± 0.18 log CFU/mL CSF/day, -0.41 ± 0.35 log CFU/mL CSF/day, and -0.44 ± 0.20 log CFU/mL CSF/day, respectively. Overall mortality was 12% (9 of 78 patients died) at 2 weeks and 29% (22 of 75 patients died) at 10 weeks, with no statistically significant differences among groups. There were few laboratory abnormalities related to the second agents given; in particular, there were no statistically significant (≥grade 3) increases in alanine transaminase level or decreases in neutrophil count. There was no statistically significant difference in EFA between AmB in combination with fluconazole and AmB plus 5-FC for the treatment of HIV-associated cryptococcal meningitis. AmB plus fluconazole (800-1200 mg/day) represents an immediately implementable alternative to AmB plus 5-FC. AmB plus voriconazole is an effective alternative combination in patients not receiving interacting medications.
    Clinical Infectious Diseases 11/2011; 54(1):121-8. DOI:10.1093/cid/cir745 · 8.89 Impact Factor
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    ABSTRACT: ABSTRACT: There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions. Participants starting ART between February 2005 and December 2006 in The AIDS Support (TASO) clinic in Jinja, Uganda, were enrolled into a cluster-randomised trial of home versus facility-based care and followed up to January 2009. The trial was integrated into normal service delivery with patients managed by TASO staff according to national guidelines. Rates of survival, virological failure, hospital admissions and CD4 count over time were similar between the two arms. Data for the present analysis were analysed using Cox regression analyses. 1453 subjects were enrolled with baseline median count of 108 cells/μl. Over time, 119 (8%) withdrew and 34 (2%) were lost to follow-up. 197/1453 (14%) died. Mortality rates (95% CI) per 100 person-years were 11.8 (10.1, 13.8) deaths in the first year and 2.4 (1.8, 3.2) deaths thereafter. The one, two and three year survival probabilities (95% CI) were 0.89 (0.87 - 0.91), 0.86 (0.84 - 0.88) and 0.85 (0.83 - 0.87) respectively. Low baseline CD4 count, low body weight, advanced clinical condition (WHO stages III and IV), not being on cotrimoxazole prophylaxis and male gender were associated independently with increased mortality. Tuberculosis, cryptococcal meningitis and diarrhoeal disease were estimated to be major causes of death. Practical and affordable interventions are needed to enable earlier initiation of ART and to reduce mortality risk among those who present late for treatment with advanced disease.
    AIDS Research and Therapy 10/2011; 8(1):39. DOI:10.1186/1742-6405-8-39 · 1.46 Impact Factor
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    ABSTRACT: As immune compromised HIV sero-positive people regain health after initiating antiretroviral treatment (ART), they may seek a return to an active 'normal' life, including sexual activity. The aim of the paper is to explore the changing sexual desires and behaviour of people on ART in Uganda over a 30 month period. This study employed longitudinal qualitative interviews with forty people starting ART. The participants received their ART, adherence education and counselling support from The AIDS Support Organisation (TASO). The participants were selected sequentially as they started ART, stratified by sex, ART delivery mode (clinic or home-based) and HIV progression stage (early or advanced) and interviewed at enrolment, 3, 6, 18 and 30 months of their ART use. Sexual desire changed over time with many reporting diminished desire at 3 and 6 months on ART compared to 18 and 30 months of use. The reasons for remaining abstinent included fear of superinfection or infecting others, fear that engaging in sex would awaken the virus and weaken them and a desire to adhere to the counsellors' health advice to remain abstinent. The motivations for resumption of sexual activity were: for companionship, to obtain material support, social norms around marriage, desire to bear children as well as to satisfy sexual desires. The challenges for most of the participants were using condoms consistently and finding a suitable sexual partner (preferably someone with a similar HIV serostatus) who could agree to have a sexual relationship with them and provide for their material needs. These findings point to the importance of tailoring counselling messages to the changing realities of the ART users' cultural expectations around child bearing, marriage and sexual desire. People taking ART require support so they feel comfortable to disclose their HIV status to sexual partners.
    BMC Public Health 08/2011; 11(1):633. DOI:10.1186/1471-2458-11-633 · 2.26 Impact Factor

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6k Citations
1,078.20 Total Impact Points


  • 1997–2015
    • London School of Hygiene and Tropical Medicine
      • • Faculty of Epidemiology and Population Health
      • • Department of Infectious Disease Epidemiology
      Londinium, England, United Kingdom
  • 2009–2010
    • Medical Research Council / Uganda Virus Research Institute
      Entebbe, Central Region, Uganda
  • 2008
    • University of Cape Town
      • Institute of Infectious Disease & Molecular Medicine (IIDMM)
      Cape Town, Province of the Western Cape, South Africa
  • 2004
    • Mahidol University
      • Department of Obstetrics and Gynecology
      Krung Thep, Bangkok, Thailand
  • 2002
    • University of Zimbabwe
      Salisbury, Harare, Zimbabwe
  • 2000
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan
    • University of Nottingham
      Nottigham, England, United Kingdom
  • 1998
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
  • 1995–1998
    • Medical Research Council Unit, The Gambia Unit
      Bakau, Banjul, Gambia