Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial

Abstract

BackgroundMalnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality.MethodsThe study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m2 who were referred for ART based on CD4 count <350 cells/μL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART.ResultsFollow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80–1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55–0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19–2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10–1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/μL (95% CI, 4–46) higher in the LNS-VM compared to the LNS arm (P = 0.02).ConclusionsHigh-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients.Trial registrationPACTR201106000300631, registered on 1st June 2011.

Malnutrition status and associated factors among HIV-positive patients enrolled in ART clinics in Zimbabwe

“…Second, the addition of micronutrient supplements to ART may provide increased nutritional recovery among HIV-positive patients with undernutrition [49,50] and also more importantly improve adherence to ART among foodinsecure adults as has been shown in Zambia [51] though no significant gains were observed with respect to weight and CD4 cell count response. However, despite improved health and ART adherence, perceptions among foodinsecure HIV-positive adults participating in one Kenyan food supplementation program highlighted the inevitability of sharing food disbursements with people outside their families thus depleting the food available for them [52].…”

“…Table 1 shows the socio-demographic characteristics of the 1,242 HIV-positive adults who were enrolled in this study. There were 849 (68%) females and the overall median age of all participants was 41 years (IQR, [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. Slightly more study participants resided in the rural areas (n = 699, 56%) compared to urban areas (n = 543, 44%).…”

A longitudinal study of systemic inflammation and recovery of lean body mass among malnourished HIV-infected adults starting antiretroviral therapy in Tanzania and Zambia

“…As part of the main study, we recruited 1876 patients (17) .This number was sufficient to detect, at 129 5% significance, 90% power and 25% attrition by 12 weeks due to death or loss to follow-up, The intra-individual changes in serum CRP from baseline to 6 weeks were inversely associated 191 with changes in several of the body composition measurements over the same period ( Table 4).…”

Acute Thymic Involution and Mechanisms for Recovery

“…Recently, the impact of nutritional intervention on the T cell subpopulation was investigated in malnourished adult HIV patients, and a lipid-based nutrient supplement with vitamins and minerals did not affect mortality or morbidity. However, it led to a significant increase in the CD4 + T cell population (Chisenga et al 2015;Filteau et al 2015).…”