Christopher Nyirenda

Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia.

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/m2 (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/m2. 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.

Serum Phosphate Predicts Early Mortality in Adults Starting Antiretroviral Therapy in Lusaka, Zambia: A Prospective Cohort Study

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/m2 or CD4+ lymphocyte count <50 cells/µL, 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.

Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia

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 ≥18.5 kg/m2), 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/μl. 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/μl increase in the first 6 months of ART. A CD4+ cell count increase of at least 100 cells/μl 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.

Cardiometabolic risk factors among HIV patients on antiretroviral therapy.

BackgroundHIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk.MethodsAdult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90 days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and ‘other’ (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen.ResultsFrom baseline to 90 days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04 mmol/L for men and <1.30 mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ≥5.18 mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ≥3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ≥5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen.ConclusionOur results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen.

Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia

BackgroundA 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.MethodsAn 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.ResultsLower 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.ConclusionsThe 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.

Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa

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.

Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia—a new context for refeeding syndrome?

High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries.

Serum Phosphate Predicts Early Mortality among Underweight Adults Starting ART in Zambia: A Novel Context for Refeeding Syndrome?

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/m2, 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/m2 (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.

Plasma Fatty Acids in Zambian Adults with HIV/AIDS: Relation to Dietary Intake and Cardiovascular Risk Factors.

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.