Article

Lawn SD, Harries AD, Anglaret X, Myer L, Wood R. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa

aDesmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa bClinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK cHIV Unit, Ministry of Health, Malawi dFamily Health International, Malawi Country Office, Lilongwe, Malawi eProgramme PAC-CI, Abidjan, Ivory Coast, France fINSERM, Unité 897, Centre de Recherche Epidémiologie et Biostatistique, Bordeaux, France gInfectious Diseases Epidemiology Unit, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa hDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
AIDS (London, England) (Impact Factor: 5.55). 11/2008; 22(15):1897-908. DOI: 10.1097/QAD.0b013e32830007cd
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ABSTRACT

Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, however, early mortality rates in sub-Saharan Africa are very high; between 8 and 26% of patients die in the first year of antiretroviral treatment, with most deaths occurring in the first few months. Patients typically access antiretroviral treatment with advanced symptomatic disease, and mortality is strongly associated with baseline CD4 cell count less than 50 cells/mul and WHO stage 4 disease (AIDS). Although data are limited, leading causes of death appear to be tuberculosis, acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome. Mortality rates are likely to depend not only on the care delivered by antiretroviral treatment programmes, but more fundamentally on how advanced disease is at programme enrollment and the quality of preceding healthcare. In addition to improving delivery of antiretroviral treatment and providing it free of charge to the patient, strategies to reduce mortality must include earlier diagnosis of HIV infection, strengthening of longitudinal HIV care and timely initiation of antiretroviral treatment. Health systems delays in antiretroviral treatment initiation must be minimized, especially in patients who present with advanced immunodeficiency.

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    • "However, high mortality in the first few months of ART remains a major concern [1,2] . Consistent risk factors for early mortality include low CD4 count, advanced WHO disease stage, the presence of opportunistic infections such as tuberculosis (TB), and malnutrition, usually indicated by low body mass index (BMI) [1,3,4]. Food insecurity, though widespread in much of Africa, is unlikely to be the main cause of low BMI among HIVinfected Africans. "
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    ABSTRACT: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/μL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART. Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/μL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients. PACTR201106000300631, registered on 1st June 2011.
    Full-text · Article · Jan 2015
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    • "Timely presentation at services and minimisation of delays in initiation of treatment have been identified as potentially important contributory factors to reducing the high levels of early mortality observed in treatment programmes for HIV/AIDS [1,2]. Recent research carried out among people living with HIV/AIDS has led to wider recognition of the important contribution of mental disorder, in particular, depression, to HIV clinical outcomes. "
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    ABSTRACT: Background Successful linkage to care is increasingly recognised as a potentially important factor in determining the success of Antiretroviral Therapy treatment programmes. However, the role of psychological factors during the early part of the continuum of care has so far been under-investigated. The objective of the Umeed study was to evaluate the impact of Common Mental Disorder (CMD), hazardous alcohol use and low cognitive functioning upon attendance for post-test counselling and linkage to care among people attending for HIV-testing in Goa, India. Methods The study was a prospective cohort design. Participants were recruited at the time of attending for testing and were asked to complete a baseline interview covering sociodemographic characteristics and mental health exposures. HIV status, post-test counselling (PTC) and Antiretroviral Treatment (ART) Centre data were extracted from clinical records. Results Among 1934 participants, CMD predicted non-attendance for PTC (adjusted OR = 0.51, 0.21-0.82). There was tentative evidence of an association between hazardous alcohol use and non-attendance for PTC (adjusted OR = 0.69, 0.45-1.02). There was no evidence of an association between CMD caseness and attendance for ART. However, post-hoc analyses showed an association between increasing symptoms of CMD and non-attendance. Conclusions Although participation rates were high (86%), non-participation was a possible source of bias. Cognitive tests had not been previously validated in a young population in Goa. The context in which cognitive testing took place may have contributed to the high prevalence of low scores. Findings suggest the need to move towards a broader conceptualisation of the interrelationship between mental health and HIV. It may be important to consider the impact of symptoms of depression and anxiety at every stage of the continuum of care, including immediately after diagnosis and when initiating contact with treatment services.
    Full-text · Article · Jun 2014 · BMC Psychiatry
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    • "However the quality of pre-ART care that they received was poor – as they remained without a recent CD4 count. It is essential that pre-ART patients have regular CD4 counts and that ART is initiated as soon as indicated to decrease morbidity and mortality associated with low CD4 counts [3], [5], [21]. Other studies confirm poor retention in and quality of pre-ART care as patients still initiate ART at low baseline CD4 counts (below 200 cells/mm3) [5]. "
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    ABSTRACT: Few studies have evaluated access to and retention in pre-ART care. To evaluate the proportion of People Living With HIV (PLWH) in pre-ART and ART care and factors associated with retention in pre-ART and ART care from a community cohort. A cross sectional survey was conducted from February - April 2011. Self reported HIV positive, negative or participants of unknown status completed a questionnaire on their HIV testing history, access to pre-ART and retention in pre-ART and ART care. 872 randomly selected adults who reported being HIV positive in the ZAMSTAR 2010 prevalence survey were included and revisited. 579 (66%) reconfirmed their positive status and were included in this analysis. 380 (66%) had initiated ART with 357 of these (94%) retained in ART care. 199 (34%) had never initiated ART of whom 186 (93%) accessed pre-ART care, and 86 (43%) were retained in pre-ART care. In a univariable analysis none of the factors analysed were significantly associated with retention in care in the pre-ART group. Due to the high retention in ART care, factors associated with retention in ART care, were not analysed further. Retention in ART care was high; however it was low in pre-ART care. The opportunity exists, if care is better integrated, to engage with clients in primary health care facilities to bring them back to, and retain them in, pre-ART care.
    Full-text · Article · May 2014 · PLoS ONE
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