Participants and study site
Eligible participants were all adults aged 18 or over with HIV who met the eligibility criteria for antiretroviral therapy according to the Malawian national HIV treatment guidelines (WHO clinical stage III or IV or any WHO stage with a CD4 count <250/mm3) and who were starting treatment with a BMI <18.5. Exclusion criteria were pregnancy and lactation or participation in another supplementary feeding programme. The study took place at the antiretroviral therapy clinic of Queen Elizabeth Central Hospital in Blantyre, Malawi, from January 2006 to April 2007.
Blantyre is the major commercial city of Malawi, with a population of 1
000 and an estimated HIV prevalence of 27% in adults in 2004.16
Clinical care for adults at this clinic is provided by the department of medicine of the College of Medicine, University of Malawi. The only available first line antiretroviral therapy regimen is a generic, fixed dose combination of nevirapine, stavudine, and lamivudine. Routine prophylaxis with co-trimoxazole before and during antiretroviral therapy had not been fully implemented at the time of the study. It was approved as a standard treatment by the Ministry of Health in 2006, but the logistics to implement this policy were not in place until 2007.
This was a randomised, investigator blinded, controlled effectiveness trial of supplementary feeding with either corn-soy blend or fortified spread. Randomisation took place with sealed, unmarked opaque envelopes that were allocated to participants in an area separate from the research and treatment room by using block randomisation of 50 numbers. The envelopes contained a card with a unique number from 1 to 500. A designated staff member matched the number with the food assignment and dispensed the appropriate food during the intervention period. Participants were not blinded to the food assignment because the blended flour was distinct in appearance compared with the peanut paste. All the other staff members, including the clinicians managing the antiretroviral therapy programme and the nutritionist, were blinded to the dietary assignment. The food supplements were distributed monthly in conjunction with clinic follow-up visits, and each of the study participants remained within the group to which they were assigned for the duration of the study. Food supplements were started at the same time as antiretroviral therapy and given for a period of 14 weeks. Participants returned for follow-up two weeks after the start of the study and monthly thereafter.
Our primary outcomes were changes in the BMI and the fat-free body mass after 14 weeks. Secondary outcomes were nutritional status, defined as well nourished (BMI ≥18.5), moderately wasted (BMI 16-<18.5), severely wasted (BMI <16), death, alive/nutritional status unknown, and lost to follow-up. Additional secondary outcomes were quality of life, serum albumin concentration, haemoglobin concentration, CD4 count, HIV viral load, and adherence to antiretroviral therapy.
The sample size of 450 enabled detection of a difference in BMI and fat-free body mass of 0.5 kg between the two groups with 95% specificity and 80% power. We allowed for 15% attrition because of pregnancy, losses to follow-up, and death.
On enrolment, we obtained informed consent and demographic, clinical status, quality of life, and anthropometric measurements; measurements included weight, height, mid-upper arm circumference, waist circumference, and bioelectrical impedance. Participants had their bioelectrical impedance measured when they presented to the clinic for care, without regard to ambient conditions or the time of day. Those who seemed clinically ill were assumed to be at risk for dehydration, and a bioelectrical impedance measurement was not recorded.
Clinical officers supervised provision of antiretroviral therapy. Participants were subsequently seen at the clinic on four occasions during the study: after two, six, 10, and 14 weeks. During each visit trained study staff assessed clinical status, administered questionnaires on quality of life and adherence to antiretroviral therapy, and measured body weight, bioelectrical impedance, and waist and mid-upper arm circumferences. They collected information on quality of life with a locally adapted version of the 14 item CDC health related quality of life assessment.17
Adherence to treatment was measured with a local, previously validated questionnaire that consisted of four questions: did you miss a tablet the day, week, month, or ever before.18
Bioelectrical impedance measurements were done with the Quaatum 2000 device (RJL Systems, Clinton Township, Michigan). All measurements were carried out with standardised procedures.
Researchers took blood samples at enrolment and at 14 weeks to measure serum albumin concentration, haemoglobin concentration, CD4 count (FacsCount, Becton-Dickinson, Franklin Lakes, NJ, USA), and HIV viral load (Roche Amplicor; Roche, Basel. Switzerland; detection level 48 copies/ml).
Participants’ diets on enrolment were assessed with a 24 hour dietary recall the day before enrolment. In addition, for each of the foods that the participants consumed the day before enrolment they were asked whether the foods were consumed daily, weekly, or monthly. Dietary intakes were assessed with three different methods: the total number of different foods consumed, whether animal products were consumed or not, and a 12 point dietary diversity score that has previously been validated and correlated with household food security.19
Participants who failed to return for a scheduled clinic visit for antiretroviral therapy were visited at home within two months, and information regarding clinical status, compliance with treatment, and body weight and composition was collected. If the participant had died, the date and circumstances of death were ascertained by interviews with the closest relatives. Participants who could not be located were considered lost to follow-up.
After the supplementary feeding period ended social scientists from the University of Malawi, who were not involved in any other aspect of the study, led open ended focus group discussions to explore the use, acceptability, and sharing of the food supplements and to assess dietary compliance; groups averaged eight randomly selected study participants from both supplementary feeding groups.
Table 1 shows the nutritional compositions of the two supplementary foods. Both supplementary foods provided the same level of energy because different amounts were used; the energy per unit higher in the fortified spread; neither provided amounts of micronutrients that significantly exceeded the estimated average requirement. The supplements were produced locally in accordance with international food safety specifications. The ready-to-use fortified spread was supplied in 245 g plastic bottles, and participants received one bottle a day. The amounts of each supplement given provided about 50% of the daily estimated average energy requirement, based on WHO nutritional guidelines that take into account that symptomatic adults with HIV/AIDS need 30% more energy than healthy individuals.20
Both groups of participants were advised to consider the food supplements as part of their medical treatment and told that the food should not be shared with others.
Table 1 Nutrients provided by two food supplements, expressed as amount per day and compared with estimated average requirement (EAR) for adults
The data were doubly entered on an Excel database. We calculated fat-free body mass using the equations developed by Kotler et al for wasted adults with HIV.21
These equations were used in our setting without validation. We calculated means and standard deviations for continuous parameters and used Fisher’s exact test (two outcomes) or χ2
test (three or more outcomes) to compare dichotomous variables between participants in each supplement group. We used Student’s t
test to compare continuous variables. P<0.05 was considered significant for all comparisons.
BMI was measured at four subsequent points after enrolment (after two, six, 10, and 14 weeks), so the participant’s recovery was assessed during each of these four distinct time intervals. We calculated the rate of change in BMI during each of these intervals for each participant. To determine whether the rates of change in BMI during the 14 week feeding period differed between the two food groups, we compared the mean change in BMI during each interval for each food group using Student’s t
test. Weight gain during recovery from wasting follows an exponential decay pattern22
; when individuals are more wasted they regain weight faster, and as they approach a normal BMI, the rate of weight gain decreases. Given this, we used the mean values for change in BMI for each food group from this study to determine the shape of the BMI recovery curve, using an exponential modeling program (GraphPad Prism 3.03).
We assessed the association between death and demographic, anthropometric, and immunological characteristics by Cox regression modeling. The covariates considered were sex, age, type of supplementary food, receipt of co-trimoxazole, BMI, fat-free body mass, CD4 count, haemoglobin concentration, and albumin concentration at enrolment. Participants who were given co-trimoxazole as prophylaxis at any time during the study period were considered as having received it in the regression analysis. SPSS version 13.0 (Chicago, IL) statistical software was used.
Participants were stratified into thirds for the three different measures of dietary intake, and we compared the change in BMI for those receiving fortified spread and corn-soy blend between each third to determine whether supplementary feeding was more beneficial among participants with more food insecurity.