Browsing by Author "Ford, Nathan"

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    AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa
    (BioMed Central Ltd., 2010) Chu, Kathryn; Mahlangeni, Gcina; Swannet, Sarah; Ford, Nathan; Boulle, Andrew; Van Cutsem, Gilles
    BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality.Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential.
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    Antiretroviral therapy outcomes among adolescents and youth in rural Zimbabwe
    (Public Library of Science, 2012) Bygrave, Helen; Mtangirwa, Judith; Ncube, Kwenzakwenkosi; Ford, Nathan; Kranzer, Katharina; Munyaradzi, Dhodho
    Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.
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    Antiretroviral treatment outcomes from a nurse-driven, community-supported HIV/AIDS treatment programme in rural Lesotho: observational cohort assessment at two years
    (BioMed Central Ltd, 2009) Cohen, Rachel; Lynch, Sharonann; Bygrave, Helen; Eggers, Evi; Vlahakis, Natalie; Hilderbrand, Katherine; Knight, Louise; Pillay, Prinitha; Saranchuk, Peter; Goemaere, Eric; Makakole, Lipontso; Ford, Nathan
    INTRODUCTION:Lesotho has the third highest HIV prevalence in the world (an adult prevalence of 23.2%). Despite a lack of resources for health, the country has implemented state-of-the-art antiretroviral treatment guidelines, including early initiation of treatment (<350 cells/mm3), tenofovir in first line, and nurse-initiated and managed HIV care, including antiretroviral therapy (ART), at primary health care level.PROGRAMME APPROACH:We describe two-year outcomes of a decentralized HIV/AIDS care programme run by Doctors Without Borders/Medecins Sans Frontieres, the Ministry of Health and Social Welfare, and the Christian Health Association of Lesotho in Scott catchment area, a rural health zone covering 14 clinics and one district hospital. Outcome data are described through a retrospective cohort analysis of adults and children initiated on ART between 2006 and 2008.DISCUSSION AND EVALUATION:Overall, 13,243 people have been enrolled in HIV care (5% children), and 5376 initiated on ART (6.5% children), 80% at primary care level. Between 2006 and 2008, annual enrolment more than doubled for adults and children, with no major external increase in human resources. The proportion of adults arriving sick (CD4 <50 cells/mm3) decreased from 22.2% in 2006 to 11.9% in 2008. Twelve-month outcomes are satisfactory in terms of mortality (11% for adults; 9% for children) and loss to follow up (8.8%). At 12 months, 80% of adults and 89% of children were alive and in care, meaning they were still taking their treatment; at 24 months, 77% of adults remained in care. CONCLUSION: Despite major resource constraints, Lesotho is comparing favourably with its better resourced neighbour, using the latest international ART recommendations. The successful two-year outcomes are further evidence that HIV/AIDS care and treatment can be provided effectively at the primary care level. The programme highlights how improving HIV care strengthened the primary health care system, and validates several critical areas for task shifting that are being considered by other countries in the region, including nurse-driven ART for adults and children, and lay counsellor-supported testing and counselling, adherence and case management.
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    Assessing the effectiveness of the ART programme in the Western Cape Province of South Africa through triangulation of context-appropriate population level routine monitoring and surveillance systems
    (2023) Osler, Margaret; Boulle, Andrew; Ford, Nathan
    Background After a decade of free antiretroviral therapy (ART) provision, countries continued facing challenges both in trying to meet the ever-increasing pool of eligible people needing HIV treatment, and efficiently monitoring programme effectiveness to improve patient care and service delivery. Concerns about the feasibility of further treatment expansion were being debated with trials showing benefit, but with ongoing uncertainty as to whether those benefits would be realised in resource-limited settings with fragile health systems. Key questions underpinning this thesis were how to robustly develop, implement, monitor and use routine health information systems to explore pertinent epidemiological questions, including real-world effectiveness of the ART programme, determinants of ongoing morbidity and mortality, and the impact of guideline changes. Methods The thesis includes a health systems review of the implementation of person-level information systems for HIV care, followed by a number of cohort analyses based on the public-sector health services in the Western Cape, South Africa. The study population consists of people living with HIV, who had at least one CD4 test or HIV-care visit, and who were ≥16 years of age. The cohort analyses utilized a population-wide linked dataset containing all available digital data from fixed health facilities, laboratory, pharmacy, and death registry systems. The first analysis described temporal trends in the CD4 distributions over 10 years, with longitudinal categorization of ART status of people with extremely advanced HIV disease (AHD). Two analyses used a regression discontinuity design to consider the causal impact of guideline changes, while the last two analyses explored important longer-duration determinants of morbidity and mortality in a survival analysis cohort framework, including through the use of flexible parametric survival models. Results Developing a tiered suite of interoperable information solutions enabled each health facility to independently evolve from paper to offline and then hybrid/online electronic registers when dependencies such as electricity, stable networks and resources allowed them to. The largest proportion of people with severe AHD (CD4 <50 cells/µL) came from those already on ART in more recent years, in comparison to people first presenting or not eligible for ART. Of those on ART with severe AHD, more than three-quarters had a confirmed treatment interruption (>3 months) and/or viraemia within the previous year. The biggest benefits (based on24-month survival) when increasing eligibility thresholds for ART were seen during earlier guideline changes which expanded access at lower CD4 count thresholds (from CD4 <200/µL to CD4 <350/µL); however, at a patient level, benefits from ART were seen at all three eligibility threshold changes (200, 350 and 500 cells/µl). Deferring treatment for people ineligible lead to, on average, >2 years delay prior to starting ART, increasing risk of AHD and death. The greatest increases in ART initiations and decreases in mortality happened between guideline changes, reflecting large increases in ART access prior to formal expansion of access through guideline changes. As the ART programme has matured, men living with HIV continue to have poorer access to ART, a greater risk of TB, are more likely to interrupt treatment and have inferior clinical outcomes compared to woman, especially between diagnosis and the first five years on ART. Women, however, carried the larger absolute mortality burden, due to the greater numbers living with HIV. Almost two-thirds of the ART cohort interrupted treatment for >4 months at least once, increasing their risk of death by 27%, compared to people who had never interrupted ART. Each additional interruption was associated with further increases in mortality. Conclusions Pragmatic interoperable offline/hybrid/online health information systems can be successfully implemented at scale in lower resource settings to improve patient care, provide information on interventions and inform policy and resource allocation. Programmatic ART outcomes did improve during expansion of ART eligibility including into the time-period of the treat-all policy when CD4 count criteria were removed. More people accessed ART over time, independent of guideline changes, improving population HIV outcomes. The guidelines changes were nonetheless shown to be effective at an individual level. The number of people with AHD has not decreased however due to ART experienced patients returning to care after interruptions with considerable immune deterioration. Recommendations focused on improving systems for retention, re-engagement, and AHD and are most likely applicable to similar public-sector settings in Southern Africa.
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    Cesarean section rates and indications in sub-Saharan Africa: a multi-country study from Medecins sans Frontieres
    (Public Library of Science, 2012) Chu, Kathryn; Cortier, Hilde; Maldonado, Fernando; Mashant, Tshiteng; Ford, Nathan; Trelles, Miguel
    Objectives The World Health Organization considers Cesarean section rates of 5-15% to be the optimal range for targeted provision of this life saving intervention. However, access to safe Cesarean section in resource-limited settings is much lower, estimated at 1-2% reported in sub-Saharan Africa. This study reports Cesarean sections rates and indications in Democratic Republic of Congo, Burundi, and Sierra Leone, and describe the main parameters associated with maternal and early neonatal mortality. METHODS: Women undergoing Cesarean section from August 1 2010 to January 31 2011 were included in this prospective study. Logistic regression was used to model determinants of maternal and early neonatal mortality. RESULTS: 1276 women underwent a Cesarean section, giving a frequency of 6.2% (range 4.1-16.8%). The most common indications were obstructed labor (399, 31%), poor presentation (233, 18%), previous Cesarean section (184, 14%), and fetal distress (128, 10%), uterine rupture (117, 9%) and antepartum hemorrhage (101, 8%). Parity >6 (adjusted odds ratio [aOR] = 8.6, P = 0.015), uterine rupture (aOR = 20.5; P = .010), antepartum hemorrhage (aOR = 13.1; P = .045), and pre-eclampsia/eclampsia (aOR = 42.9; P = .017) were associated with maternal death. Uterine rupture (aOR = 6.6, P<0.001), anterpartum hemorrhage (aOR = 3.6, P<0.001), and cord prolapse (aOR = 2.7, P = 0.017) were associated with early neonatal death. CONCLUSIONS: This study demonstrates that target Cesarean section rates can be achieved in sub-Saharan Africa. Identifying the common indications for Cesarean section and associations with mortality can target improvements in antenatal services and emergency obstetric care.
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    CMV retinitis screening and treatment in a resource-poor setting: three-year experience from a primary care HIV/AIDS programme in Myanmar
    (BioMed Central Ltd, 2011) Tun, NiNi; London, Nikolas; Kyaw, Moe; Smithuis, Frank; Ford, Nathan; Margolis, Todd; Drew, W Lawrence; Lewallen, Susan; Heiden, David
    BACKGROUND: Cytomegalovirus retinitis is a neglected disease in resource-poor settings, in part because of the perceived complexity of care and because ophthalmologists are rarely accessible. In this paper, we describe a pilot programme of CMV retinitis management by non-ophthalmologists. The programme consists of systematic screening of all high-risk patients (CD4 <100 cells/mm3) by AIDS clinicians using indirect ophthalmoscopy, and treatment of all patients with active retinitis by intravitreal injection of ganciclovir. Prior to this programme, CMV retinitis was not routinely examined for, or treated, in Myanmar. METHODS: This is a retrospective descriptive study. Between November 2006 and July 2009, 17 primary care AIDS clinicians were trained in indirect ophthalmoscopy and diagnosis of CMV retinitis; eight were also trained in intravitreal injection. Evaluation of training by a variety of methods documented high clinical competence. Systematic screening of all high-risk patients (CD4 <100 cells/mm3) was carried out at five separate AIDS clinics throughout Myanmar. RESULTS: A total of 891 new patients (1782 eyes) were screened in the primary area (Yangon); the majority of patients were male (64.3%), median age was 32 years, and median CD4 cell count was 38 cells/mm3. CMV retinitis was diagnosed in 24% (211/891) of these patients. Bilateral disease was present in 36% of patients. Patients with active retinitis were treated with weekly intravitreal injection of ganciclovir, with patients typically receiving five to seven injections per eye. A total of 1296 injections were administered. CONCLUSIONS: A strategy of management of CMV retinitis at the primary care level is feasible in resource-poor settings. With appropriate training and support, CMV retinitis can be diagnosed and treated by AIDS clinicians (non-ophthalmologists), just like other major opportunistic infections.
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    Correcting for mortality among patients lost to follow up on antiretroviral therapy in South Africa: a cohort analysis
    (Public Library of Science, 2011) Van Cutsem, Gilles; Ford, Nathan; Hildebrand, Katherine; Goemaere, Eric; Mathee, Shaheed; Abrahams, Musaed; Coetzee, David; Boulle, Andrew
    BACKGROUND: Loss to follow-up (LTF) challenges the reporting of antiretroviral treatment (ART) programmes, since it encompasses patients alive but lost to programme and deaths misclassified as LTF. We describe LTF before and after correction for mortality in a primary care ART programme with linkages to the national vital registration system. Methods and FINDINGS: We included 6411 patients enrolled on ART between March 2001 and June 2007. Patients LTF with available civil identification numbers were matched with the national vital registration system to ascertain vital status. Corrected mortality and true LTF were determined by weighting these patients to represent all patients LTF. We used Kaplan-Meier estimates and Cox regression to describe LTF, mortality among those LTF, and true LTF. Of 627 patients LTF, 85 (28.8%) had died within 3 months after their last clinic visits. Respective estimates of LTF before and after correction for mortality were 6.9% (95% confidence interval [CI] 6.2-7.6) and 4.3% (95% CI 3.5-5.3) at one year on ART, and 23.9% (95% CI 21.0-27.2) and 19.7% (95% CI 16.1-23.7) at 5 years. After correction for mortality, the hazard of LTF was reversed from decreasing to increasing with time on ART. Younger age, higher baseline CD4 count, pregnancy and increasing calendar year were associated with higher true LTF. Mortality of patients LTF at 1, 12 and 24 months after their last visits was respectively 23.1%, 30.9% and 43.8%; 78.0% of deaths occurred during the first 3 months after last visit and 45.0% in patients on ART for 0 to 3 months. CONCLUSIONS: Mortality of patients LTF was high and occurred early after last clinic visit, especially in patients recently started on ART. Correction for these misclassified deaths revealed that the risk of true LTF increased over time. Research targeting groups at higher risk of LTF (youth, pregnant women and patients with higher CD4 counts) is needed.
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    Density of healthcare providers and patient outcomes: evidence from a nationally representative multi-site HIV treatment program in Uganda
    (Public Library of Science, 2011) Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Zhang, Wendy; Hagopian, Amy; Ford, Nathan; Mills, Edward J
    Objective We examined the association between density of healthcare providers and patient outcomes using a large nationally representative cohort of patients receiving combination antiretroviral therapy (cART) in Uganda. Design We obtained data from The AIDS Support Organization (TASO) in Uganda. Patients 18 years of age and older who initiated cART at TASO between 2004 and 2008 contributed to this analysis. The number of healthcare providers per 100 patients, the number of patients lost to follow-up per 100 person years and number of deaths per 100 person years were calculated. Spearman correlation was used to identify associations between patient loss to follow-up and mortality with the healthcare provider-patient ratios. RESULTS: We found no significant associations between the number of patients lost to follow-up and physicians ( p  = 0.45), nurses ( p  = 0.93), clinical officers ( p  = 0.80), field officers ( p  = 0.56), and healthcare providers overall ( p  = 0.83). Similarly, no significant associations were observed between mortality and physicians ( p  = 0.65), nurses ( p  = 0.49), clinical officers ( p  = 0.73), field officers ( p  = 0.78), and healthcare providers overall ( p  = 0.73). CONCLUSIONS: Patient outcomes, as measured by loss to follow-up and mortality, were not significantly associated with the number of doctors, nurses, clinical officers, field officers, or healthcare providers overall. This may suggest that that other factors, such as the presence of volunteer patient supporters or broader political or socioeconomic influences, may be more closely associated with outcomes of care among patients on cART in Uganda.
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    Does direct observation of antiretroviral therapy improve outcomes for HIV/AIDS patients compared to non-observed therapy?: A systematic review and meta-analysis of randomized-controlled trials
    (2009) Ford, Nathan; Engel, Mark E
    Highly active antiretroviral therapy (HAART) has dramatically affected the course of HIV disease, resulting in a significant reduction in AIDS-related morbidity and mortality in both developed and developing countries.
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    Early adherence to antiretroviral medication as a predictor of long-term HIV virological suppression: five-year follow up of an observational cohort
    (Public Library of Science, 2010) Ford, Nathan; Darder, Marta; Spelman, Tim; Maclean, Emi; Mills, Edward; Boulle, Andrew
    Objective Previous studies have demonstrated a cross-sectional relationship between antiretroviral adherence and HIV virological suppression. We assessed the predictive value of baseline adherence in determining long-term virological failure. Design We assessed baseline adherence via an adherence questionnaire between administered to all consenting patients attending antiretroviral clinics in Khayelitsha township, South Africa, between May 2002 and March 2004. Virological status was ascertained after five years of follow up and multivariate analysis used to model associations of baseline variables and medication adherence with time to viral suppression or failure. RESULTS: Our adherence cohort comprised 207 patients, among whom 72% were female. Median age was 30 years and median CD4 count at initiation was 55 cells/mm 3 . We found no statistically significant differences between baseline characteristics and early adherence groups. Multivariate analysis adjusting for baseline CD4 and age found that patients with suboptimal baseline adherence had a hazard ratio of 2.82 (95% CI 1.19-6.66, p = 0.018) for progression to virological failure compared to those whose baseline adherence was considered optimal. CONCLUSIONS: Our longitudinal study provides further confirmation of adherence as a primary determinant of subsequent confirmed virological failure, and serves as a reminder of the importance of initial early investments in adherence counseling and support as an effective way to maximize long-term treatment success.
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    Effectiveness of patient adherence groups as a model of care for stable patients on antiretroviral therapy in Khayelitsha, Cape Town, South Africa
    (Public Library of Science, 2013) Luque-Fernandez, Miguel Angel; Cutsem, Gilles Van; Goemaere, Eric; Hilderbrand, Katherine; Schomaker, Michael; Mantangana, Nompumelelo; Mathee, Shaheed; Dubula, Vuyiseka; Ford, Nathan; Hernán, Miguel A
    BACKGROUND: Innovative models of care are required to cope with the ever-increasing number of patients on antiretroviral therapy in the most affected countries. This study, in Khayelitsha, South Africa, evaluates the effectiveness of a group-based model of care run predominantly by non-clinical staff in retaining patients in care and maintaining adherence. Methods and FINDINGS: Participation in "adherence clubs" was offered to adults who had been on ART for at least 18 months, had a current CD4 count >200 cells/ml and were virologically suppressed. Embedded in an ongoing cohort study, we compared loss to care and virologic rebound in patients receiving the intervention with patients attending routine nurse-led care from November 2007 to February 2011. We used inverse probability weighting to estimate the intention-to-treat effect of adherence club participation, adjusted for measured baseline and time-varying confounders. The principal outcome was the combination of death or loss to follow-up. The secondary outcome was virologic rebound in patients who were virologically suppressed at study entry. Of 2829 patients on ART for >18 months with a CD4 count above 200 cells/µl, 502 accepted club participation. At the end of the study, 97% of club patients remained in care compared with 85% of other patients. In adjusted analyses club participation reduced loss-to-care by 57% (hazard ratio [HR] 0.43, 95% CI = 0.21-0.91) and virologic rebound in patients who were initially suppressed by 67% (HR 0.33, 95% CI = 0.16-0.67). DISCUSSION: Patient adherence groups were found to be an effective model for improving retention and documented virologic suppression for stable patients in long term ART care. Out-of-clinic group-based models facilitated by non-clinical staff are a promising approach to assist in the long-term management of people on ART in high burden low or middle-income settings.
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    The first decade of antiretroviral therapy in Africa
    (BioMed Central Ltd, 2011) Ford, Nathan; Calmy, Alexandra; Mills, Edward
    The past decade has seen remarkable progress in increasing access to antiretroviral therapy in resource-limited settings. Early concerns about the cost and complexity of treatment were overcome thanks to the efforts of a global coalition of health providers, activists, academics, and people living with HIV/AIDS, who argued that every effort must be made to ensure access to essential care when millions of lives depended on it. The high cost of treatment was reduced through advocacy to promote access to generic drugs; care provision was simplified through a public health approach to treatment provision; the lack of human resources was overcome through task-shifting to support the provision of care by non-physicians; and access was expanded through the development of models of care that could work at the primary care level. The challenge for the next decade is to further increase access to treatment and support sustained care for those on treatment, while at the same time ensuring that the package of care is continuously improved such that all patients can benefit from the latest improvements in drug development, clinical science, and public health.
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    An integrated approach of community health worker support for HIV/AIDS and TB care in Angonia district, Mozambique
    (BioMed Central Ltd, 2009) Simon, Sandrine; Chu, Kathryn; Frieden, Marthe; Candrinho, Baltazar; Ford, Nathan; Schneider, Helen; Biot, Marc
    BACKGROUND:The need to scale up treatment for HIV/AIDS has led to a revival in community health workers to help alleviate the health human resource crisis in sub-Saharan Africa. Community health workers have been employed in Mozambique since the 1970s, performing disparate and fragmented activities, with mixed results. METHODS: A participant-observer description of the evolution of community health worker support to the health services in Angonia district, Mozambique. RESULTS: An integrated community health team approach, established jointly by the Ministry of Health and Medecins Sans Frontieres in 2007, has improved accountability, relevance, and geographical access for basic health services. CONCLUSION: The community health team has several advantages over 'disease-specific' community health worker approaches in terms of accountability, acceptability, and expanded access to care.
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    Keeping health staff healthy: evaluation of a workplace initiative to reduce morbidity and mortality from HIV/AIDS in Malawi
    (BioMed Central Ltd, 2011) Bemelmans, Marielle; van den Akker, Thomas; Pasulani, Olesi; Tayub, Nabila; Hermann, Katharina; Mwagomba, Beatrice; Jalasi, Winnie; Chiomba, Harriet; Ford, Nathan; Philips, Mit
    BACKGROUND: In Malawi, the dramatic shortage of human resources for health is negatively impacted by HIV-related morbidity and mortality among health workers and their relatives. Many staff find it difficult to access HIV care through regular channels due to fear of stigma and discrimination. In 2006, two workplace initiatives were implemented in Thyolo District: a clinic at the district hospital dedicated to all district health staff and their first-degree relatives, providing medical services, including HIV care; and a support group for HIV-positive staff. METHODS: Using routine programme data, we evaluated the following outcomes up to the end of 2009: uptake and outcome of HIV testing and counselling among health staff and their dependents; uptake and outcomes of antiretroviral therapy (ART) among health staff; and membership and activities of the support group. In addition, we included information from staff interviews and a job satisfaction survey to describe health workers' opinions of the initiatives. RESULTS: Almost two-thirds (91 of 144, 63%) of health workers and their dependents undergoing HIV testing and counselling at the staff clinic tested HIV positive. Sixty-four health workers had accessed ART through the staff clinic, approximately the number of health workers estimated to be in need of ART. Of these, 60 had joined the support group. Cumulative ART outcomes were satisfactory, with more than 90% alive on treatment as of June 2009 (the end of the study observation period). The availability, confidentiality and quality of care in the staff clinic were considered adequate by beneficiaries. CONCLUSIONS: Staff clinic and support group services successfully provided care and support to HIV-positive health workers. Similar initiatives should be considered in other settings with a high HIV prevalence.
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    Male gender predicts mortality in a large cohort of patients receiving antiretroviral therapy in Uganda
    (BioMed Central Ltd, 2011) Mills, Edward; Bakanda, Celestin; Birungi, Josephine; Chan, Keith; Hogg, Robert; Ford, Nathan; Nachega, Jean; Cooper, Curtis
    BACKGROUND:Because men in Africa are less likely to access HIV/AIDS care than women, we aimed to determine if men have differing outcomes from women across a nationally representative sample of adult patients receiving combination antiretroviral therapy in Uganda. METHODS: We estimated survival distributions for adult male and female patients using Kaplan-Meier, and constructed multivariable regressions to model associations of baseline variables with mortality. We assessed person-years of life lost up to age 55 by sex. To minimize the impact of patient attrition, we assumed a weighted 30% mortality rate among those lost to follow up. RESULTS: We included data from 22,315 adults receiving antiretroviral therapy. At baseline, men tended to be older, had lower CD4 baseline values, more advanced disease, had pulmonary tuberculosis and had received less treatment follow up (all at p < 0.001). Loss to follow up differed between men and women (7.5 versus 5.9%, p < 0.001). Over the period of study, men had a significantly increased risk of death compared with female patients (adjusted hazard ratio 1.43, 95% CI 1.31-1.57, p < 0.001). The crude mortality rate for males differed importantly from females (43.9, 95% CI 40.7-47.0/1000 person-years versus 26.9, 95% CI 25.4-28.5/1000 person years, p < 0.001). The probability of survival was 91.2% among males and 94.1% among females at 12 months. Person-years of life lost was lower for females than males (689.7 versus 995.9 per 1000 person-years, respectively). CONCLUSIONS: In order to maximize the benefits of antiretroviral therapy, treatment programmes need to be gender sensitive to the specific needs of both women and men. Particular efforts are needed to enroll men earlier into care.
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    Mortality after fluid bolus in children with shock due to sepsis or severe infection: a systematic review and meta-analysis
    (Public Library of Science, 2012) Ford, Nathan; Hargreaves, Sally; Shanks, Leslie
    Introduction Sepsis is one of the leading causes of childhood mortality, yet controversy surrounds the current treatment approach. We conducted a systematic review to assess the evidence base for fluid resuscitation in the treatment of children with shock due to sepsis or severe infection. METHODS: We searched 3 databases for randomized trials, quasi-randomized trials, and controlled before-after studies assessing children with septic shock in which at least one group was treated with bolus fluids. The primary outcome was mortality at 48 hours. Assessment of methodological quality followed the GRADE criteria. Relative risks (RRs) and 95% confidence intervals (CI) were calculated and data pooled using fixed-effects method. RESULTS: 13 studies met our inclusion criteria. No bolus has significantly better mortality outcomes at 48 hours for children with general septic shock (RR 0.69; 95%CI 0.54-0.89), and children with malaria (RR 0.64; 95%CI 0.45-0.91) when compared to giving any bolus. This result is largely driven by a single, high quality trial (the FEAST trial). There is no evidence investigating bolus vs no bolus in children with Dengue fever or severe malnutrition. Colloid and crystalloid boluses were found to have similar effects on mortality across all sub-groups (general septic shock, malaria, Dengue fever, and severe malnutrition). CONCLUSIONS: The majority of all randomized evidence to date comes from the FEAST trial, which found that fluid boluses were harmful compared to no bolus. Simple algorithms are needed to support health-care providers in the triage of patients to determine who could potentially be harmed by the provision of bolus fluids, and who will benefit.
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    Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa
    (Public Library of Science, 2010) Chu, Kathryn M; Boulle, Andrew M; Ford, Nathan; Goemaere, Eric; Asselman, Valerie; Van Cutsem, Gilles
    BACKGROUND: The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality. CONCLUSIONS: The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria.
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    Outcomes for efavirenz versus nevirapine-containing regimens for treatment of HIV-1 infection: a systematic review and meta-analysis
    (Public Library of Science, 2013) Pillay, Prinitha; Ford, Nathan; Shubber, Zara; Ferrand, Rashida A
    Introduction There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART). METHODS: We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I 2 statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds. RESULTS: Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I 2  = 0%) and observational studies (RR 0.65 [0.59-0.71] I 2  = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I 2  = 0%) and observational studies (RR 1.06 [1.00-1.12] I 2  = 68%). CONCLUSION: EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.
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    Priorities for developing countries in the global response to non-communicable diseases
    (BioMed Central Ltd, 2012) Maher, Dermot; Ford, Nathan; Unwin, Nigel
    The growing global burden of non communicable diseases (NCDs) is now killing 36 million people each year and needs urgent and comprehensive action. This article provides an overview of key critical issues that need to be resolved to ensure that recent political commitments are translated into practical action. These include: (i) categorizing and prioritizing NCDs in order to inform donor funding commitments and priorities for intervention; (ii) finding the right balance between the relative importance of treatment and prevention to ensure that responses cover those at risk, and those who are already sick; (iii) defining the appropriate health systems response to address the needs of patients with diseases characterized by long duration and often slow progression; (iv) research needs, in particular translational research in the delivery of care; and (v) sustained funding to support the global NCD response.
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    Provision and continuation of antiretroviral therapy during acute conflict: the experience of MSF in Central African Republic and Yemen
    (BioMed Central, 2018-07-02) Ferreyra, Cecilia; O’Brien, Daniel; Alonso, Beatriz; Al-Zomour, Abdulbasset; Ford, Nathan
    Background: Unstable settings present challenges for the effective provision of antiretroviral treatment (ART). In this paper, we summarize the experience and results of providing ART and implementing contingency plans during acute instability in the Central African Republic (CAR) and Yemen. Case presentation: In CAR, MSF has provided HIV care in three conflict-affected rural regions; these were put on hold throughout the acute phase of violence. “Run-away bags” containing 3 or 4 months of ART were distributed to patients at MSF facilities. Among 1820 HIV patients enrolled into care, 1440 (79%) initiated ART. By December 2016, 782 (54%) patients were still under ART, 354 (25%) have been lost to follow up and 182 (13%) had died. In 2013, when violence disrupted services, 683 patients were receiving ART. Between September–December 2013, 594 (87%) patients received runaway bags and by February 2014, 313 (53%) of these patients returned to the clinic. In Yemen, when violence erupted, patients received a health card that included a helpline to call in case of drug shortages in admission to emergency stocks; this was not possible in CAR due to lack of a functioning telephone network. One thousand six hundred fifty-five PLWHA have been enrolled in care and 1470 (89%) initiated ART; 1056 (72%) are still followed on ART, 126 (9%) were lost to follow up, and 288 (20%) died. In January 2011 clashes began and by April 2011 MSF medical activities were interrupted. Of the 363 patients receiving ART, 363 (100%) received emergency bags to cover 9 months and by February 2012, 354 (98%) patients returned to care. In March 2015 a new wave of conflict affected Yemen, forcing HIV activities to revert to contingency planning. Conclusions: This experience provides further evidence that provision of HIV treatment and emergency drug stocks can be successfully provided to most patients in both conflict-affected settings.