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Weight change at 1 mo of antiretroviral therapy and its association with subsequent mortality, morbidity, and CD4 T cell reconstitution in a Tanzanian HIV-infected adult cohort.

ABSTRACT: The development of low-cost point-of-care technologies to improve HIV treatment is a major focus of current research in resource-limited settings.We assessed associations of body mass index (BMI; in kg/m(2)) at antiretroviral therapy (ART) initiation and weight change after 1 mo of treatment with mortality, morbidity, and CD4 T cell reconstitution.A prospective cohort of 3389 Tanzanian adults initiating ART enrolled in a multivitamin trial was followed at monthly clinic visits (median: 19.7 mo). Proportional hazard models were used to analyze mortality and morbidity associations, whereas generalized estimating equations were used for CD4 T cell counts.The median weight change at 1 mo of ART was +2.0% (IQR: -0.4% to +4.6%). The association of weight loss at 1 mo with subsequent mortality varied significantly by baseline BMI (P = 0.011). Participants with ?2.5% weight loss had 6.43 times (95% CI: 3.78, 10.93 times) the hazard of mortality compared with that of participants with weight gains ?2.5%, if their baseline BMI was <18.5 but only 2.73 times (95% CI: 1.49, 5.00 times) the hazard of mortality if their baseline BMI was ?18.5 and <25.0. Weight loss at 1 mo was also associated with incident pneumonia (P = 0.002), oral thrush (P = 0.007), and pulmonary tuberculosis (P < 0.001) but not change in CD4 T cell counts (P > 0.05).Weight loss as early as 1 mo after ART initiation can identify adults at high risk of adverse outcomes. Studies identifying reasons for and managing early weight loss are needed to improve HIV treatment, with particular urgency for malnourished adults initiating ART. The parent trial was registered at clinicaltrials.gov as NCT00383669.

SUBMITTER: Sudfeld CR

PROVIDER: S-EPMC3652924 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Weight change at 1 mo of antiretroviral therapy and its association with subsequent mortality, morbidity, and CD4 T cell reconstitution in a Tanzanian HIV-infected adult cohort.

Sudfeld Christopher R CR Isanaka Sheila S Mugusi Ferdinand M FM Aboud Said S Wang Molin M Chalamilla Guerino E GE Giovannucci Edward L EL Fawzi Wafaie W WW

The American journal of clinical nutrition 20130501 6

<h4>Background</h4>The development of low-cost point-of-care technologies to improve HIV treatment is a major focus of current research in resource-limited settings.<h4>Objective</h4>We assessed associations of body mass index (BMI; in kg/m(2)) at antiretroviral therapy (ART) initiation and weight change after 1 mo of treatment with mortality, morbidity, and CD4 T cell reconstitution.<h4>Design</h4>A prospective cohort of 3389 Tanzanian adults initiating ART enrolled in a multivitamin trial was ...[more]

PMID: 23636235

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Project description:BackgroundLong-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery.Methods and findingsCD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4-17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n?=?914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization-recommended CD4 thresholds for starting ART in children ?5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled.ConclusionsAlthough younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and Prevention guidelines. In contrast, to maximise CD4 reconstitution in treatment-naïve children >10 y, ART should ideally be considered even if there is a low risk of immediate disease progression. Further exploration of the immunological mechanisms for these CD4 recovery profiles should help guide management of paediatric HIV infection and optimise children's immunological development. Please see later in the article for the Editors' Summary.

Project description:BackgroundCD4(+) T-lymphocyte count (CD4 count) is a standard method used to monitor HIV-infected patients during anti-retroviral therapy (ART). The World Health Organization (WHO) has pointed out or recommended that a handheld, point-of-care, reliable, and affordable CD4 count platform is urgently needed in resource-scarce settings.MethodsHIV-infected patient blood samples were tested at the point-of-care using a portable and label-free microchip CD4 count platform that we have developed. A total of 130 HIV-infected patient samples were collected that included 16 de-identified left over blood samples from Brigham and Women's Hospital (BWH), and 114 left over samples from Muhimbili University of Health and Allied Sciences (MUHAS) enrolled in the HIV and AIDS care and treatment centers in the City of Dar es Salaam, Tanzania. The two data groups from BWH and MUHAS were analyzed and compared to the commonly accepted CD4 count reference method (FACSCalibur system).ResultsThe portable, battery operated and microscope-free microchip platform developed in our laboratory (BWH) showed significant correlation in CD4 counts compared with FACSCalibur system both at BWH (r?=?0.94, p<0.01) and MUHAS (r?=?0.49, p<0.01), which was supported by the Bland-Altman methods comparison analysis. The device rapidly produced CD4 count within 10 minutes using an in-house developed automated cell counting program.ConclusionsWe obtained CD4 counts of HIV-infected patients using a portable platform which is an inexpensive (<$1 material cost) and disposable microchip that uses whole blood sample (<10 µl) without any pre-processing. The system operates without the need for antibody-based fluorescent labeling and expensive fluorescent illumination and microscope setup. This portable CD4 count platform displays agreement with the FACSCalibur results and has the potential to expand access to HIV and AIDS monitoring using fingerprick volume of whole blood and helping people who suffer from HIV and AIDS in resource-limited settings.

Dataset Information

Weight change at 1 mo of antiretroviral therapy and its association with subsequent mortality, morbidity, and CD4 T cell reconstitution in a Tanzanian HIV-infected adult cohort.

Publications

Weight change at 1 mo of antiretroviral therapy and its association with subsequent mortality, morbidity, and CD4 T cell reconstitution in a Tanzanian HIV-infected adult cohort.

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