Browsing by Author "Koethe JR"

Now showing 1 - 10 of 10

A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.
(2010-Mar-12) Koethe JR; Westfall AO; Luhanga DK; Clark GM; Goldman JD; Mulenga PL; Cantrell RA; Chi BH; Zulu I; Saag MS; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604.
Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia.
(2010-Apr-01) Koethe JR; Lukusa A; Giganti MJ; Chi BH; Nyirenda CK; Limbada MI; Banda Y; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To describe the association between 6-month weight gain on antiretroviral therapy (ART) and subsequent clinical outcomes. DESIGN: A retrospective analysis of a large programmatic cohort in Lusaka, Zambia. METHODS: Using Kaplan-Meier analysis and Cox proportional hazards models, we examined the association between 6-month weight gain and the risk of subsequent death and clinical treatment failure. Because it is a known effect modifier, we stratified our analysis according to body mass index (BMI). RESULTS: Twenty-seven thousand nine hundred fifteen adults initiating ART were included in the analysis. Patients in the lower BMI categories demonstrated greater weight gain. In the post 6-month analysis, absolute weight loss was strongly associated with mortality across all BMI strata, with the highest risk observed among those with BMI <16 kg/m (adjusted hazard ratio 9.7; 95% CI: 4.7 to 20.0). There seemed to be an inverse relationship between weight gain and mortality among patients with BMI <16 kg/m. Similar trends were observed with clinical treatment failure. CONCLUSIONS: Weight gain after ART initiation is associated with improved survival and decreased risk for clinical failure, especially in the lower BMI strata. Prospective trials to promote weight gain after ART initiation among malnourished patients in resource-constrained settings are warranted.
Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia.
(2010-Aug-24) Koethe JR; Limbada MI; Giganti MJ; Nyirenda CK; Mulenga L; Wester CW; Chi BH; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To evaluate the relationship between early CD4(+) lymphocyte recovery on antiretroviral therapy (ART) and subsequent survival among low body mass index (BMI) HIV-1-infected adults. DESIGN: Retrospective analysis of a large programmatic cohort in Lusaka, Zambia. METHODS: We evaluated ART-treated adults enrolled in care for more than 6 months. We stratified this study population according to World Health Organization (WHO) malnutrition criteria: normal (BMI >or=18.5 kg/m(2)), mild (17.00-18.49), moderate (16.00-16.99), and severe (<16.0). We used Cox proportional hazards regression to estimate the subsequent risk of death associated with absolute CD4(+) cell count change over the first 6 months on ART. To account for effect modification associated with baseline CD4(+) cell count, a weighted summary measure was calculated. RESULTS: From May 2004 to February 2009, 56,612 patients initiated ART at Lusaka district clinics; of these, 33 097 (58%) were included in this analysis. The median change in 0-6 month CD4(+) cell count in each baseline BMI strata varied from 127 to 131 cells/microl. There was a statistically significant, inverse association between baseline BMI and the post 6-month hazard for mortality only among those patients with less than 100 cells/microl increase in the first 6 months of ART. A CD4(+) cell count increase of at least 100 cells/microl over the first 6 months of ART was not associated with a higher hazard for mortality, regardless of baseline BMI. CONCLUSIONS: Low baseline BMI and attenuated CD4(+) cell count response at 6 months had a compounding, negative impact on post 6-month survival. Specific guidelines for monitoring ART response using immunologic criteria may be warranted for low BMI patients.
Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting.
(2014) Koethe JR; Marseille E; Giganti MJ; Chi BH; Heimburger D; Stringer JS; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Division of Infectious Diseases, Vanderbilt University School of Medicine, 215 Light Hall, Nashville, TN 37232, USA.; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Vanderbilt Institute for Global Health, 2525 West End Ave., Nashville, TN 37203, USA.; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Department of Obstetrics and Gynecology, UNC Global Women's Health, University of North Carolina at Chapel Hill School of Medicine, 3009 Old Clinic Building CB #7570, Chapel Hill, NC 27599-7570, USA.; Health Strategies International, 555 59th Street, Oakland, CA 94609, USA.; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Department of Biostatistics, Vanderbilt University School of Medicine, 215 Light Hall, Nashville, TN 37232, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. METHODS: We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m(2)), moderate (16.00-16.99 kg/m(2)), and mild (17.00-18.49 kg/m(2)) malnutrition categories. RESULTS: 19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m(2) category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m(2) patients. Among BMI 17.00-18.49 kg/m(2) patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. CONCLUSIONS: Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata.
Macronutrient supplementation for malnourished HIV-infected adults: a review of the evidence in resource-adequate and resource-constrained settings.
(2009-Sep-01) Koethe JR; Chi BH; Megazzini KM; Heimburger DC; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Access to antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has expanded rapidly throughout sub-Saharan Africa, but malnutrition and food insecurity have emerged as major barriers to the success of ART programs. Protein-calorie malnutrition (a common form of malnutrition in the region) hastens HIV disease progression, and food insecurity is a barrier to medication adherence. Analyses of patient outcomes have identified a low body mass index after the start of ART as an independent predictor of early mortality, but the causes of a low body mass index are multifactorial (eg, normal anthropometric variation, chronic inadequate food intake, and/or wasting associated with HIV infection and other infectious diseases). Although there is much information on population-level humanitarian food assistance, few data exist to measure the effectiveness of macronutrient supplementation or to identify individuals most likely to benefit. In this report, we review the current evidence supporting macronutrient supplementation for HIV-infected adults, we report on clinical trials in resource-adequate and resource-constrained settings, and we highlight priority areas for future research.
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.
Plasma Fatty Acids in Zambian Adults with HIV/AIDS: Relation to Dietary Intake and Cardiovascular Risk Factors.
(2015) Nyirenda CK; Kabagambe EK; Koethe JR; Kiage JN; Chi BH; Musonda P; Blevins M; Bosire CN; Tsai MY; Heimburger DC; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37203, USA.; Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.; Centre for Infectious Disease Research in Zambia, 10101 Lusaka, Zambia ; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Ndola Central Hospital, School of Medicine, 10101 Ndola, Zambia ; School of Medicine, Copperbelt University, 10101 Ndola, Zambia ; Vanderbilt Institute for Global Health, Vanderbilt University, Nashville, TN 37203, USA.; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Nutritional Epidemiology Branch, Bethesda, MD 20850, USA.; Vanderbilt Institute for Global Health, Vanderbilt University, Nashville, TN 37203, USA ; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37203, USA.; Vanderbilt Institute for Global Health, Vanderbilt University, Nashville, TN 37203, USA ; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.; Vanderbilt Institute for Global Health, Vanderbilt University, Nashville, TN 37203, USA ; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37203, USA.; Centre for Infectious Disease Research in Zambia, 10101 Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Objective. To determine whether 24 hr dietary recalls (DR) are a good measure of polyunsaturated fatty acid (PUFA) intake when compared to plasma levels, and whether plasma PUFA is associated with markers of HIV/AIDS progression and cardiovascular disease (CVD) risk. Methods. In a cross-sectional study among 210 antiretroviral therapy-naïve HIV-infected adults from Lusaka, Zambia, we collected data on medical history and dietary intake using 24 hr DR. We measured fatty acids and markers of AIDS progression and CVD risk in fasting plasma collected at baseline. Results. PUFA intakes showed modest correlations with corresponding plasma levels; Spearman correlations were 0.36 (p < 0.01) for eicosapentaenoic acid and 0.21 (p = 0.005) for docosahexaenoic acid. While there were no significant associations (p > 0.05) between total plasma PUFA and C-reactive protein (CRP) or lipid levels, plasma arachidonic acid was inversely associated with CRP and triglycerides and positively associated with HDL-C, CD4+ T-cell count, and plasma albumin (p < 0.05). Plasma saturated fatty acids (SFA) were positively associated with CRP (β = 0.24; 95% CI: 0.08 to 0.40, p = 0.003) and triglycerides (β = 0.08; 95% CI: 0.03 to 0.12, p < 0.01). Conclusions. Our data suggest that a single DR is inadequate for assessing PUFA intake and that plasma arachidonic acid levels may modulate HIV/AIDS progression and CVD risk.
Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa.
(2013-Mar) Koethe JR; Blevins M; Bosire C; Nyirenda C; Kabagambe EK; Mwango A; Kasongo W; Zulu I; Shepherd BE; Heimburger DC; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression. DESIGN: A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models. SETTING: A public-sector HIV clinic in Lusaka, Zambia. SUBJECTS: One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/μl. RESULTS: Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/μl, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported. CONCLUSIONS: Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted.
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.