Browsing by Author "Chiasera JM"

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Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia.
(2011-Apr-10) Koethe JR; Blevins M; Nyirenda C; Kabagambe EK; Shepherd BE; Wester CW; Zulu I; Chiasera JM; Mulenga LB; Mwango A; Heimburger DC; Centre for Infectious Diseases Research in Zambia, Plot 1275 Lubuto Road, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described. METHODS: An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m2 or CD4+ lymphocyte counts of less than 50 cells/mm3, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality. RESULTS: Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p<0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not. CONCLUSIONS: The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.
Serum Phosphate Predicts Early Mortality among Underweight Adults Starting ART in Zambia: A Novel Context for Refeeding Syndrome?
(2013) Koethe JR; Blevins M; Nyirenda CK; Kabagambe EK; Chiasera JM; Shepherd BE; Zulu I; Heimburger DC; Centre for Infectious Diseases Research in Zambia, Plot 1275 Lubuto Road, P.O. Box 34681, Lusaka 10101, Zambia ; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, A2200-MCN, 1161 21st Avenue South, Nashville, TN 37232-2582, USA ; Vanderbilt Institute for Global Health, 2525 West End Avenue, Suite 750, Nashville, TN 37203, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Serum phosphate predicts early mortality in adults starting antiretroviral therapy in Lusaka, Zambia: a prospective cohort study.
(2010-May-18) Heimburger DC; Koethe JR; Nyirenda C; Bosire C; Chiasera JM; Blevins M; Munoz AJ; Shepherd BE; Potter D; Zulu I; Chisembele-Taylor A; Chi BH; Stringer JS; Kabagambe EK; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. douglas.heimburger@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Patients starting antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression. METHODOLOGY/PRINCIPAL FINDINGS: An observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI) <16 kg/m(2) or CD4(+) lymphocyte count <50 cells/microL, or both, was followed prospectively during the first 12 weeks of ART. Detailed health and dietary intake history, review of systems, physical examination, serum metabolic panel including phosphate, and serum ferritin and high-sensitivity C-reactive protein (hsCRP) were monitored. The primary outcome was mortality. Baseline serum phosphate was a significant predictor of mortality; participants alive at 12 weeks had a median value of 1.30 mmol/L (interquartile range [IQR]: 1.04, 1.43), compared to 1.06 mmol/L (IQR: 0.89, 1.27) among those who died (p<0.01). Each 0.1 mmol/L increase in baseline phosphate was associated with an incremental decrease in mortality (AHR 0.83; 95% CI 0.72 to 0.95). The association was independent of other metabolic parameters and known risk factors for early ART-associated mortality in sub-Saharan Africa. While participant attrition represented a limitation, it was consistent with local program experience. CONCLUSIONS/SIGNIFICANCE: Low serum phosphate at ART initiation was an independent predictor of early mortality among HIV patients starting ART with severe malnutrition or advanced immunosuppression. This may represent a physiologic phenomenon similar to refeeding syndrome, and may lead to therapeutic interventions that could reduce mortality.