A number of additional randomised and quasi-randomised, controlled studies have compared two or more oral nutritional supplements with each other. The majority of these studies were conducted in the USA23–29, with three studies conducted in Africa30–32 and one study each conducted in Germany33, Switzerland34 and Spain35, respectively. The effects of various nutritional supplements on outcomes such as body weight, body composition, dietary intake, HIV-associated diarrhoea, immune parameters, viral load, quality of life and progression of the disease have been investigated in HIV-infected adults and children.
The studies are grouped by intervention investigated and discussed below.
Balanced nutritional supplements
Three small, randomised trials23, 24, 35 compared the effects of supplementation with standard nutritional formula (ENSURE®) and a peptide-based formula (ADVERA®) in adults (age: ±38 years, CD4+: 178−561, BMI: ±21), for time periods ranging from 6 weeks24 to 6 months23. The peptide-based formula used has a higher caloric density, 4%
more protein and 15% more fat (as a percentage of the total calories), and is enriched with n-3 polyunsaturated fatty acids. Two out of the three studies provided nutritional counselling to all participants23, 35.
After 6 weeks of supplementation no significant difference was noted in nutrient intake, body weight or body composition between the two groups24. However, both nutritional formulas significantly increased total energy (ENSURE® mean difference 15%
of needs.day-1, p<0.05; ADVERA® mean difference 7% of needs.day-1, p<0.05) and total protein intake (ENSURE® mean difference 15% of needs.day-1, p<0.05; ADVERA® mean difference 17% of needs.day-1, p<0.05) from baseline levels.
After three months of supplementation an increase in body weight from baseline values was noted for both formulas (ENSURE® 3.2%, p<0.05; ADVERA® 3.1%, p<0.05);
although this was mainly due to an increase in fat mass35. Compared with baseline values, CD4+ count remained stable in the standard formula group and increased significantly in the peptide-based formula group (576±403 vs 642±394 cells.mm-3, p<0.05)35.
After 6 months of supplementation, participants receiving the peptide-based formula gained a significantly greater amount of weight compared with those receiving the standard formula (mean difference between the two groups, post intervention = 5.5kg;
95% CI: 4.97 to 6.03). Furthermore, those receiving the peptide-based formula had significantly fewer unscheduled hospitalisations compared with the standard formula group (ADVERA® 0 visits vs ENSURE® 36 visits, p<0.05)23.
Medium-chain fatty acid-containing triglycerides (MCT) and long-chain fatty acid-containing triglycerides (LCT)
Two small, randomised controlled trials compared the effect of 12 days of supplementation with MCT- and LCT-based formulas on fat absorption and body weight in participants (age: 32–38 years, CD4+: 63−179, BMI: ±19) in the USA26, 27. Compared with ingestion of LCT formula, ingestion of MCT formula significantly increased fat absorption, in both studies (4.3±5.8 vs –1.1±5.8 g.day-1 fat absorption, p<0.04,26; 5.4±0.6 vs 12±2.6 g.day-1 faecal fat excretion, p<0.01,27). No significant change in body weight was noted in any of the participants in either of the studies.
A further trial compared the effect of supplements containing either peptides and MCTs or whole proteins and LCTs on body weight and body cell mass of HIV-infected individuals25. Throughout the 4 months, both the supplemented groups and the non-
supplemented control groups received a multivitamin and mineral supplement. No differences in percent change in body weight or body cell mass were noted within or between either of the groups.
Specific amino acids and polyunsaturated fatty acids
In a quasi-randomised, controlled trial, a six-week supplementation with fish oil bars enriched with n-3 polyunsaturated fatty acids, compared with safflower oil supplementation, resulted in a non-significant decrease in CD4+ cell count in HIV- infected individuals29. In a randomised, controlled trial, six months supplementation with either a standard nutritional supplement or a standard nutritional supplement enriched with arginine and n-3 polyunsaturated fatty acids resulted in an increase in total energy intake, body weight and fat mass34. No change was noted in immune or viral parameter over the six months in either of the groups34.
In a controlled, crossover phase trial, HIV-infected adults (N=10, age: 44±3.5, CD4+: 286±47, BMI: 22.3±0.8) receiving a standard formula (liquid formula containing 500 kcal/500ml of which 17% protein, 25% fat and 53% carbohydrates) enriched with arginine, α-linoleic acid and ribonucleic acid for 16 weeks gained a significantly greater amount of weight compared with those receiving the standard formula alone (mean difference in weight between the two groups post intervention 3.4kg 95% CI: 1.51 to 5.29)36. While no significant changes were noted in circulating lymphocytes, serum concentrations of tumor necrosis factor-alpha receptors, sTNFR 55 (mean difference 0.63 ng.ml-1; 95% CI: 0.39 to 0.87) and sTNFR 75 (mean difference 1.26 ng.ml-1 95% CI:
0.48 to 2.04), were significantly elevated following supplementation with the enriched formula compared with the standard formula36. While serum concentrations of sTNFR reflect TNF release and levels increase with HIV disease progression, sTNFR also act as neutalising agents limiting the systemic catabolic effects of TNF36.
In a randomised crossover trial, malnourished (HIV-infected participants (age:37±12 yrs, BMI: 18.6±1.3, CD4+: 176±203) were supplemented with a polymeric diet (consisting of whole proteins rather than specific amino acids) and regular food for two consecutive 45-day periods. Compared with regular food, supplementation with the polymeric diet resulted in significant improvements in body weight (mean difference 2.9kg 95% CI: 0.61 to 5.19) and fat-free mass (mean difference 1.59kg 95% CI: 0.09 to 3.09). No significant changes were noted in CD4+ or CD8+ cell count or plasma albumin levels37.
Ready-to-use therapeutic food in African children
The effect of ready-to-use therapeutic food has been investigated in malnourished HIV-infected and non-infected African children. Ready-to-use therapeutic food is an energy-dense liquid paste made from peanut butter, milk powder, oil, sugar, vitamins
and minerals. In a quasi-randomised, controlled trial, ready-to-use therapeutic food (energy content: 175kcal/kg/day) was compared with a ready-to-use therapeutic food supplement (energy content: 500kcal/day) and a blended maize/soy flour mix (energy content: 175kcal/kg/day) in severely malnourished (weight-for-height Z score: ± −1.8 to –2.8) HIV-infected children in Malawi (N=93, age: ±24 to 27 months)30. Fifty-six percent of the children reached 100% weight-for-height (by weight-for-height Z score standards based on children’s height at admission), with those receiving ready-to-use therapeutic food gaining weight more rapidly and being significantly more likely to reach 100%
weight-for-height (RR 1.62 95% CI: 1.01 to 2.59) than those receiving the ready-to-use therapeutic food supplement or the maize/soy flour mix. In an earlier quasi-randomised, controlled trial imported and locally produced ready-to-use therapeutic food was similarly effective in treating severe malnutrition (weight-for-height Z score: ± −2.1 to –2.2) in HIV-infected (N=78) and non-infected children (N=182)32.
In Zambia, 4 weeks supplementation with infant formula feed (Neocate, SHS International, Liverpool, United Kingdom) containing amino acids, maltodextrin and a combination of safflower oil, coconut oil and soya oil (energy content: 70 kcal/100ml;
vitamin and mineral content similar to that of breastmilk) resulted in significantly greater weight gain (weight-for-height Z score) in malnourished HIV-infected (N=106;
mean difference 1.0 95% CI: 0.87 to 1.13) and non-infected children (N=90; mean difference 0.39 95% CI: 0.28 to 0.5), compared with those in the control group31. The control group received a liquid feed containing a mixture of skimmed milk, sugar and vegetable oil (energy content: 100kcal/100ml; vitamin and mineral content not specified) for the first two weeks, following which they were fed a high-energy protein porridge (energy content: 400kcal/100ml).