Nutritional Support to HIV Patients Starting ART.

Abstract

To the Editors: We welcome the systematic review1 on nutrition assessment, counseling, and support interventions among people with HIV/AIDS. The review emphasizes the need for well-conducted trials to inform policy makers but also mentions the ethical challenges of designing studies with unsupplemented control groups, and the possible role of duration and timing of supplementation. The authors searched literature databases from January 1995 to May 2014. Of 4 randomized food intervention trials identified, only 1 had an unsupplemented control group, and the report from that study does not seem to have been peer reviewed and published (KEMRI, 2012). In fact, another 2 randomized nutrition intervention trials could have been included if the authors had also searched databases of registered trials. The ARTFood trial, published in May 2014,2 randomized 282 HIV-infected Ethiopian patients [with body mass index (BMI) >17 kg/m2] to lipid-based nutrient supplements (LNS) with either whey or soy protein, for the first 3 months of antiretroviral therapy (ART) or the subsequent 3 months. As such, it was possible to have an unsupplemented comparison group over the first 3 months, but also, although with limited power, to explore the effect of early versus late supplementation. In addition, patients with BMI between 16 and 17 kg/m2 were randomized to receive LNS in the first 3 months of ART to support comparison of whey and soy. Those with BMI below 16 kg/m2 were excluded and referred to standard care of severe malnutrition. The primary outcome was accumulation of lean body mass, measured using the deuterium dilution technique, as well as grip strength and physical activity. After 3 months, those receiving LNS had increased weight by 2.05 kg in addition to the 0.87 kg weight gain among those receiving only ART. Of the 2.05 kg effect on weight, 0.90 kg was lean mass. Those only on ART had no increase in lean mass at all. The effect on lean mass was accompanied by an increase in grip strength, but not in physical activity. Interestingly, LNS with whey was associated with a marginally significant increase in CD4 count (25 cells/μL; 95% confidence interval: −2 to 53), and significant increments in CD3 and CD8. We found it justified to have an unsupplemented (delayed supplementation) control group for patients with a BMI above 17 kg/m2, not least because mortality during commencement of ART in Ethiopia is low but also because it is plausible that supplementation may be more beneficial when given with some delay. First, until inflammation has faded, the nutrients provided may not be absorbed and metabolized effectively to result in regain of muscles and organs, and recovery of immune and other body functions. Second, early supplementation may also result in refeeding hypophosphatemia. The latter was addressed in the NUSTART trial, which randomized 1815 malnourished (BMI <18.5 kg/m2) Tanzanian and Zambian adults starting ART to LNS either with no additional fortification or with high levels of vitamins and minerals (LNS-VM).3 There were no treatment group differences in mortality (primary outcome) but the additional vitamins and minerals in LNS-VM compared with LNS alone resulted in a greater increase in CD4 count by 12 weeks of ART (25 cells/μL; 95% confidence interval: 4 to 46), increases in some anthropometric measures, fewer episodes of low plasma phosphate but more episodes of high plasma phosphate and potassium.3,4 Therefore, although some clinical benefits were seen and hypophosphatemia was reduced, the LNS-VM may have been fortified with levels of potassium and phosphate in excess of what could be safely handled by these seriously ill malnourished patients. The ARTFood and NUSTART trials, together with previous studies included in the systematic review,1 suggest that there may be merit in integrating short course LNS into treatment of African patients starting ART, particularly if they are also malnourished. Issues about vitamin and mineral fortificant levels, timing of the LNS in relation to appetite changes at the start of ART,5 and duration of the intervention would need to be addressed. As discussed by Tang et al,1 such supplementation is only one component of the nutritional interventions required for people with HIV and needs to be combined with nutritional counseling and assessment interventions.