Nutritional status, specifically maintenance of protein stores, impacts on the individual's ability to survive with HIV infection by reducing a person's total immune system which in turn increases a person's total energy demands (Steenkamp & Danabauser, 2001). Malnutrition increases susceptibility to infection and is an important factor in fuelling the HIV epidemic in poor countries (Garbus, 2001; MacDougall, 2002). Once HIV infection occurs, this may further aggravate nutritional status by interfering with caloric intake, nutrient absorption and energy expenditure (Donald & Kotle, 2002).
Malnutrition associated with HIV infection can be separated into two categories; starvation and cachexia (Steenkamp & Danabauser, 2001). In starvation the body does not receive the quantity and quality of nutrients required due to lack of food intake or inability to absorb nutrients. Cachexia, on the other hand, is severe weight loss due to changes in metabolism in response to HIV infection. Cachexia is characterized by greater loss of lean body mass mostly in muscles and major organs such as liver, heart, lungs and kidneys (Kotler, 1992). The metabolic changes of cachexia are thought to be regulated by the same chemical messengers that control immune function.
In HIV infected children the clinical picture is complicated by metabolic demands underlying growth and development. The required caloric intake of normally growing children with HIV infection is about one third higher than the standard requirement (MacDougall, 2002). Both the resting energy expenditure (REE) and the total energy expenditure (TEE) are increased in HIV infected individuals and have recently been correlated with viral load (MacDougall, 2002).
Dietary therapy is an important adjunct in the clinical care of patients infected with HIV. It is believed that achieving and maintaining optimal balanced dietary therapy will improve the individuals' immune function; reduce the incidence of complications associated with HIV infection; attenuate the progression of HIV infection; improve the quality of life and ultimately reduce mortality associated to HIV infection (Donald & Kotle, 2002). These effects should also lead to a reduction in the overall cost of health care.
In this review the concept of a balance diet is used to refer to a regular intake of nutritious meals that contain all the essential nutrients that cannot be synthesised in adequate quantities by the body. Nutritional interventions refer to strategies used to promote a balanced diet. A balanced diet should be adequate for growth, energy needs, nitrogen equilibrium, repair of worn out tissues and maintenance of normal health. A balanced diet can be maintained by eating a combination of various food groups such as appropriate staples, sugars, legumes, animal products, fruits, vegetables, nuts, fats and oils (Food and Agriculture Organization, 2002).
There is an urgent need to systematically review the existing research on the effectiveness of macronutrients for improving outcomes in persons with HIV infection, especially those living in developing countries. This evidence will guide health professionals in managing malnutrition associated with HIV infection. The effects of dietary therapy should be evaluated at each stage of HIV infection.
The objective of this review is to evaluate the effectiveness of various nutritional interventions with macronutrients such a balanced diet, proteins, carbohydrates, and lipids given orally in reducing morbidity and mortality in adults and children living with HIV infection worldwide.
Criteria for considering studies for this review
Types of studies
Randomized controlled trials (RCTs) that evaluate the effectiveness of various nutritional interventions, such as a balanced diet and specific macronutrients versus no nutritional therapy in the management of individuals living with HIV infection. Studies will be included regardless of the setting in which they were administered.
Studies in pregnant women will not be included.
This review will also exclude studies that have assessed the effects of micronutrient supplementation and parenteral nutrients on outcomes in HIV/AIDS. A Cochrane review examining the effects of micronutrients in reducing morbidity and mortality among HIV infected children and adults is underway (Irham, Visser, Siegfried & Rollins, 2002).
Types of participants
Children or adults living with HIV/AIDS worldwide, regardless of the stage of the disease.
Types of intervention
1. Balanced nutritional therapy given orally to individuals living with HIV infection over a period of time. Balanced diet includes macronutrients such as carbohydrates, proteins, fats, vitamins and mineral salts given in the form of food or snacks to meet the nutritional requirement of a person living with HIV infection.
2. High energy diet including lipids and sugars given to compensate for the specific individual's' energy demands.
3. High protein diet specifically designed to address or cater to the individual's' protein demands.
Only studies offering the above interventions for at least 4 weeks will be considered.
No nutritional therapy.
Types of outcome measures
1. All causes of mortality.
2. Mortality related to HIV infection and other HIV related conditions.
3. Morbidity (frequency, types and duration of episodes of opportunistic infections, hospital admissions and other types of illnesses related to HIV infection as reported in each study).
1. Disease progression according to WHO or CDC staging system as recorded in each study.
2. Indices of viral load.
3. Markers of immune response (absolute CD4+ T-lymphocyte count and CD4+ percent of total lymphocytes).
4. Nutritional status measurements such as body weight, body mass index (BMI), energy expenditure, biochemical markers such as serum albumin.
5. Dietary intake and appetite.
Search methods for identification of studies
See: Cochrane HIV/AIDS Group methods used in reviews.
See: Collaborative Review Group search strategy.
We will develop a comprehensive, unbiased search strategy to ensure that as many relevant studies as possible are included in the review. An attempt will be made to identify all relevant studies regardless of language or publication status (published or unpublished, in press or in progress).
We will search The Cochrane HIV/AIDS Group specialized trials register, the Cochrane Controlled Trials Register published in the Cochrane Library, MEDLINE, EMBASE, LILACS ( La LiteraturaLatinamericano y del caribe de Informacion en Ciencias de la Salud), and AIDSLINE for relevant trials using topic search terms in combination with the search strategy developed by The Cochrane Collaboration and detailed in the Cochrane Reviewers Handbook (Clarke 2001). These search strategies will be combined with the optimal search strategy for RCTs designed by the UK Cochrane centre (Clarke 2001). Search terms will include: balanced diet or nutrition or supplementation or protein or carbohydrates or lipids or malnutrition or cachexia and HIV infection or AIDS or AIDS wasting syndrome.
We will search conference proceedings for relevant abstracts. The proceedings to be serached include International AIDS conferences, International conferences on HIV/AIDS in Africa, International conferences on Nutrition and HIV infection, International conferences on Dietetics, International Association of Physicians in AIDS Care, International conferences on Retroviruses and Opportunist infections, National HIV/AIDS nutrition conference.
We will check reference list of all relevant articles that are obtained including those from previously published systematic reviews. Additional potential relevant articles will be retrieved and assessed for possible inclusion in the review.
We will also consult colleagues and research organizations in the field of HIV/AIDS and diet for ongoing research and recent trials that are not yet published, completed trials that were never published and unpublished technical reports and dissertations.
Methods of the review
See: Collaborative Review Group Guidelines
We (SM and DM) will screen all citations and abstracts. We will independently apply the prespecified selection criteria to identify the relevant studies. If there is uncertainty concerning eligibility of a particular study, we will obtain the full article. We will resolve our differences by discussing them with the third reviewer (JV). Where disagreements cannot be resolved, we will seek clarification from the study authors before reaching a decision. We will exclude all studies that do not meet the criteria, stating the reasons for exclusion.
Assessment of the methodological quality
We (SM and DM) will independently assess the methodological quality of the included trails using the following criteria;
(1) Generation of allocation sequence will be considered adequate if methods such as tables of random numbers, computer generated random or coin tossing were used. We will use a classification derived from the Jadad scale, viz. A = truly random, B = quasi random, C = alternate, D = unclear (Jadad, 1996).
(2) Concealment of allocation will be considered adequate if methods such as central randomization, sequentially numbered, sealed opaque envelopes were used classifying into the following categories - A = adequate, B = inadequate. C = unclear.
(3) Blinding. Studies will be assessed for blinding of investigators and/or outcome assessors. A = yes, B = no, C = unclear.
(4) Completeness of follow-up: We will record the adequacy of follow-up. A >80% B< =80%, C =unclear.
We will classify trials as having a low risk of bias if all the above criteria are met. Moderate risk of bias if one, or more criteria partially met; high risk of bias if one or more criteria are not met. The third reviewer will review the application of the assessment criteria if there is discrepancy between the findings of the two reviewers. When necessary, we will contact trial authors for clarification.
SM and DM will independently extract data using a standardized data extraction form. We will collect and code data relating to study design, participant characteristics, interventions and outcomes and enter them into Review Manager (RevMan). Discrepancies between data extracted by the two reviewers will be resolved by discussion and if required referral to the third reviewer (JV)
We will analyze data using RevMan. We will calculate relative risk, or risk difference for dichotomous data and weighted mean difference or standardized mean difference for continuous data. We will asssess precision using 95% confidence interval. We will test for heterogeneity between studies using Chi-square test of homogeneity.
We will assess heterogeneity through visual examination of the forest plot and by statistical Chi -square for heterogeinity using a 10% level of significance. In the absence of homogeneity of treatment effects, a random effect model will be used. Clinical heterogeneity is anticipated based on the age of participants. We will therefore conduct separate analyses for children and adults. We will also explore heterogeneity based on sex, socioecomomic status, ethnicity and stage of HIV infection. To assess the likelihood of publication bias, we will examine a funnel plot for asymmetry.
If possible we will conduct a sensitivity analysis to determine the degree to which the results are influenced by the adequacy of allocation concealment.
Potential conflict of interest
We declare that we have no affiliation with or involvement in any organization or entity with a different financial interest in the subject matter of review for example employment, consultancy, stock ownership, honoraria or expert testimony.
This protocol was developed with the guidance and mentorship program organized by the HIV/AIDS Group.
Sources of support
External sources of support
- SOUTH AFRICAN COCHRANE CENTER SOUTH AFRICA
- COCHRANE HEALTH PROMOTION AND PUBLIC HEALTH FIELD AUSTRALIA
Internal sources of support
- UNIVERSITY OF NATAL, DURBAN SOUTH AFRICA