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: 6.56). 11/2008; 22(15):1897-908. DOI: 10.1097/QAD.0b013e32830007cd
Source: PubMed

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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    • "Risk factors for IRIS include disseminated OI disease; recent OI treatment; low baseline CD4 with rapid rise after starting cART; and high baseline HIV VL with rapid decline after starting cART [14] [17] [20] [21]. Paradoxical IRIS in HIV-positive patients with previously treated cryptococcal disease has been estimated between 4 and 30% and is associated with an exaggerated T-cell mediated production of interferon-gamma to pathogen specific antigens [10] [12] [18] [22] [23]. The most common presentations of cryptococcal IRIS are either meningitis or lymphadenitis [24]. "
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    ABSTRACT: Background. HIV-positive people starting combined antiretroviral therapy may develop immune reconstitution to latent or treated opportunistic infections. Immune reconstitution to cerebral Cryptococcus is poorly understood and can be fatal. Case Presentation. A 33-year-old Zimbabwean female presented with cryptococcal meningitis and newly diagnosed HIV with a CD4 count of 51 cells/μL (4%). She was treated with amphotericin and flucytosine. Combined antiretroviral therapy was started four weeks later and she showed early improvement. However, over the ensuing 18 months, her clinical course was marked by periodic worsening with symptoms resembling cryptococcal meningitis despite having achieved CD4 counts ≥400 cells/μL. Although initially treated for relapsing cryptococcal immune reconstitution syndrome, a brain biopsy taken 17 months after initial presentation showed budding Cryptococci. Conclusion. This unusually protracted case highlights the difficulties in differentiating relapsing cryptococcal meningitis from immune reconstitution and raises questions concerning the optimum timing of initiation of combined antiretroviral therapy in such patients.
    03/2014; 2014:164826. DOI:10.1155/2014/164826
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    • "Early mortality in the initial 90 days after antiretroviral therapy (ART) initiation is strikingly high among persons with low body mass index (BMI < 18.5 kg/m 2 ) compared to those with normal BMI [1] [2] [3] [4]. While a greater incidence of opportunistic infections and more advanced immunosuppression likely contributes to increased mortality in undernourished patients [5] [6], the loss of metabolically active tissue may negatively impact a range of critical physiologic processes and also contribute to these early deaths [7] [8] [9]. "
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    ABSTRACT: Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI <18.5 kg/m(2), 28 (19%) died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR) 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; P = 0.01) after adjusting for sex, age, and CD4(+) lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m(2) (OR 0.96, 95% CI: 0.76 to 1.21; P = 0.74). Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed.
    Journal of nutrition and metabolism 04/2013; 2013:545439. DOI:10.1155/2013/545439
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    • "Our case studies therefore suggest that a synergistic relationship may exist between timeous receipt of this grant and improved health outcomes on ART. Several studies have shown that the first six months to a year of treatment is crucial and determines whether the treatment will be successful; those who survive this period have a reduced risk of both morbidity and mortality (Bussmann et al., 2008; Lawn et al., 2008). Our case studies show that timely receipt of the disability grant enabled household members to respond to the nutritional and health care needs of the sick member during this decisive period. "
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    ABSTRACT: This paper explores the implications of the disability grant for household members’ well-being and adults’ success on ART (antiretroviral therapy). It uses case studies based on data from an in-depth qualitative study of 10 households in KwaZulu-Natal. Receipt of the disability grant ensured that the basic needs of the HIV-infected adult could be met by other household members, especially when the grant was received when the person first met the qualifying criteria and in conjunction with ART. Where treatment was effective, HIV-infected adults were able to make substantial contributions to the well-being of other members in addition to the financial support provided by the grant itself. Thus, early access to financial support in conjunction with commencing ART may lead to improved health outcomes and reduce poverty and vulnerability associated with illness in poor households. This synergistic relationship between social welfare and treatment may in turn contribute to greater cost-efficiency.
    Development Southern Africa 03/2013; 30(1):135-147. DOI:10.1080/0376835X.2013.755767 · 0.43 Impact Factor
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