Risk factors for high early mortality in patients on antiretroviral therapy in a rural district of Malawi

Ministry of Health, Malawi, Lilongwe, Central Region, Malawi
AIDS (Impact Factor: 5.55). 11/2006; 20(18):2355-60. DOI: 10.1097/QAD.0b013e32801086b0
Source: PubMed


Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality.
A cross-sectional analytical study set in Thyolo district, Malawi.
Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined.
A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P </= 0.001) and decreasing CD4 cell counts (chi for trend = 72.4, P </= 0.001). Individuals who were severely malnourished [body mass index (BMI) < 16.0 kg/m] had a six times higher risk of dying in the first 3 months than those with a normal nutritional status.
Among individuals starting ART, the BMI and clinical staging could be important screening tools for use to identify and target individuals who, despite ART, are still at a high risk of early death.

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Available from: Simon D Makombe
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    • "Although increased availability of first line HAART in LMICs has significantly reduced mortality and morbidity amongst people living with HIV/AIDS (PLA), undernutrition and weight loss persist [17,23,24]. Both act as strong predictors of excessive early mortality [35,37,40,41]; possibly through poor immune reconstitution secondary to deficient nutritional status in PLA. With the rapid scale-up of ART programs, concerns have also been growing about the sustainability and effectiveness of such programs [14]. "
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    ABSTRACT: Over 850 million people worldwide and 200 million adults in Sub-Saharan Africa suffer from malnutrition. Countries most affected by HIV are also stricken by elevated rates of food insecurity and malnutrition. HIV infection and insufficient nutritional intake are part of a vicious cycle that contributes to immunodeficiency and negative health outcomes. However, the effect of the overlap between HIV infection and undernutrition on the immune response following antiretroviral initiation remains unclear. A possible explanation could be the lack of consensus concerning the definition and assessment of nutritional status. Our objectives are to investigate the existence of an association between undernutrition and immune response at antiretroviral treatment initiation and the following year in low- and middle-income countries where malnutrition is most prevalent.Methods/design: Our systematic review will identify studies originating from low- and middle-income countries (LMICs) published from 1996 onwards, through searches in MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and grey literature. No language restrictions will be applied. We will seek out studies of any design investigating the association between the nutritional status (for example, undernourished versus well nourished) and the immune response, either in terms of CD4 count or immune failure, in seropositive patients initiating antiretroviral therapy or in their first year of treatment. Two reviewers will independently screen articles, extract data and assess scientific quality using standardized forms and published quality assessment tools tailored for each study design. Where feasible, pooled measures of association will be obtained through meta-analyses. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. This protocol has been registered in the PROSPERO database (registration number: CRD42014005961). Undernutrition and weight loss are prevalent amongst highly active antiretroviral therapy (HAART)-treated patients in LMICs and contribute to excess early mortality. A possible intermediate pathway could be poor immune reconstitution secondary to deficient nutritional status. In the face of limited access to second line treatments, raising HIV resistance and cut backs to HIV programs, it is crucial to identify the factors associated with suboptimal response and therapeutic failure in order to better customize the care strategies employed in LMICs.
    Full-text · Article · Feb 2014 · Systematic Reviews
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    • "Low baseline CD4 cell count and perhaps more aggressive HIV have been reported in Africa.1,2,12,26,28 Although people living with HIV/AIDS in sub-Saharan Africa tend to start HAART much later compared to other settings, the effects of time-dependent prognostic factors on ART outcomes are more widely investigated in Europe and North America. "
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    ABSTRACT: CD4 T lymphocytes remain the surrogate measure for monitoring HIV progress in resource-limited settings. The absolute CD4 cell counts form the basis for antiretroviral therapy (ART) initiation and monitoring among HIV-infected adults. However, the rate of CD4 cell change differs among patients, and the factors responsible are inadequately documented. This study investigated the relationship between HIV severity and ART outcomes among ART-naïve Ugandans, with the primary outcome of complete immunological recovery among patients of different baseline CD4 counts. Patients' records at two HIV/ART sites - the Joint Clinic Research Centre (JCRC) in the Kampala region and Mbarara Hospital in Western Uganda - were reviewed. Records of 426 patients - 68.3% female and 63.2% from JCRC - who initiated ART between 2002 and 2007 were included. HIV severity was based on baseline CD4 cell counts, with low counts considered as severe immunosuppression, while attaining 418 CD4 cells/μL signified complete immunological recovery. Incidence rates of complete immunological recovery were calculated for, and compared between baseline CD4 cell categories: <50 with ≥50, <100 with ≥100, <200 with ≥200, and ≥200 with ≥250 cells/μL. The incidence of complete immunological recovery was 158 during 791.9 person-years of observation, and patients with baseline CD4 ≥ 200 cells/μL reached the end point of immunological recovery 1.89 times faster than the patients with baseline CD4 < 200 cells/μL. CD4 cell change also differed by time, sex, and site, with a faster increase observed during the first year of treatment. CD4 cell increase was faster among females, and among patients from Mbarara. Initiating ART at an advanced HIV stage was the main reason for poor immunological recovery among Ugandans. Earlier ART initiation might lead to better immunological responses.
    Full-text · Article · Dec 2013 · HIV/AIDS - Research and Palliative Care
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    • "The few studies of this topic that are available have indicated that, in Southern and Eastern Africa, fewer men than women have been accessing ART (5–8). In addition, other studies have shown that men start using ART late, when HIV is already advanced (9, 10). Similar observations have been made in Tanzania (11–14), but these studies fell short of explaining the cause of the gender gap. "
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