Body mass index, immune recovery and survival: an important but understudied relationship

Abstract

The relationship between HIV and malnutrition, which often coexist geographically, is complex and poorly understood in terms of the origins and causes of malnutrition in both treated and untreated HIV disease. Undernutrition impacts on optimal immune function; HIV in itself causes wasting. Energy requirements increase by approximately 10% in asymptomatic HIV-infected adults to maintain body weight and physical activity [1], partly explained by increased resting energy expenditure [2–4]; energy requirements are higher for symptomatic patients or those with opportunistic infections [1]. However, despite the success of increasing availability and effectiveness of highly active antiretroviral treatment (HAART) in reducing mortality at individual and population level, malnutrition and HIV-related wasting continue to increase mortality risk in treated and untreated individuals [5,6]. The study by Koethe et al.[7] in this issue of AIDS adds to the scientific evidence of the complex interplay between nutrition and HAART-related immune response. This is one of few studies reporting on the association between body mass index (BMI), CD4 cell levels and survival in 33 097 adult patients initiating antiretroviral treatment (ART) in a resource-limited government programme in Zambia. Patients were stratified according to their initial BMI and further by change in their CD4 cell count from baseline to 6 months. A low baseline BMI, together with an increase in CD4 cell count below 100 cells/μl 6 months post-treatment initiation, was independently negatively associated with survival. Compared to the reference group of patients with highest baseline BMI at least 18.5 kg/m2 and a CD4 cell count increase of at least 300 cells/μl in 6 months, those in the lowest BMI category (<16 kg/m2) with a CD4 cell count increase of 0–99 cells/μl at 6 months were nearly four times as likely to die; those in the same BMI class who experienced a CD4 decline were at approximately six times increased risk. However, patients with a CD4 recovery of at least 100 cells/μl were not at increased hazard for mortality irrespective of their baseline BMI. With the rapid global scale-up of HIV treatment, concerns around sustainability of programmes and an urgent need to seriously address ‘task shifting’, robust algorithms to identify patients at risk of poorer clinical outcomes who warrant more careful and frequent follow-up are required. This study highlights the importance of supporting all patients with low initial BMI, and in particular those with a low initial BMI who do not demonstrate a CD4 cell count increase of over 100 cells/μl after 6 months on ART. The study addresses BMI and not micronutrients. Currently, patients in this government programme with a poor nutritional state are prescribed multivitamins, but the authors indicate that there is no formal nutritional programme to deal with macronutrient insufficiency; a situation similar to many settings in sub-Saharan Africa. The authors acknowledge that issues of causality were not addressed; and the question remains what is most important to survival– an improved CD4 cell count increase, increased calories, or both. Whilst awaiting further research and given the close association between HIV and nutrition, nutritional interventions should be an integral part of all HIV treatment programmes. However, nutritional issues are often ignored in the urgency to roll-out HIV treatment, with counsellors, nurses and physicians receiving little training or guidance on monitoring and managing the nutritional aspects of HIV. A Cochrane database systematic review (soon to be updated) concluded that the current evidence base on the effectiveness of macronutrient supplementation interventions for HIV-infected people is extremely limited [8]; further research is required on the best ways to address undernutrition in HIV-infected patients. Given the current global economic situation and associated rising costs, food insecurity will continue to increase and fewer resources will be available for nutritional interventions in HIV programmes. However, HIV drug treatment may be suboptimal without close attention to nutrition; we ignore the nutritional aspects of HIV at our peril.