The care and support of people living with HIV (PLHIV) has evolved rapidly with the widespread introduction of effective antiretroviral therapy (ART). Despite substantial improvements in morbidity and mortality, ART alone has not eliminated the need to be concerned about the nutritional status of PLHIV. Although uncontrolled or advanced HIV infection is associated with weight loss and severe wasting, numerous studies in low-resource settings have shown that clinical undernutrition [as indicated by low body mass index (BMI)] at the time of ART initiation is a strong and independent predictor of mortality.1–11 In addition, HIV infection exists in geographical areas where there is high prevalence of noncommunicable diseases (diabetes, cancer, and cardiovascular disease), food insecurity, and other endemic infections (e.g., malaria, TB, and diarrheal diseases). The overlap of these conditions, which all have significant nutritional consequences and often occur within the same patient, requires a comprehensive approach to nutritional assessment and care.
Although ART initiation is associated with weight gain12 and early weight gain on ART is associated with survival, particularly among those with low BMI at baseline,11,12 it remains unclear whether nutritional interventions to improve weight/BMI before or at ART initiation will improve subsequent clinical outcomes. In 2003, the World Health Organization (WHO) provided the following guidance on nutrient requirements for adults living with HIV/AIDS: (1) adequate nutrition, which is best achieved through consumption of a balanced healthy diet, is vital for health and survival for all individuals regardless of HIV status; (2) energy requirements are likely to increase by 10% to maintain body weight and physical activity in asymptomatic HIV-infected adults; and (3) during symptomatic HIV, and subsequently during AIDS, energy requirements increase by approximately 20%–30% to maintain adult body weight.13 However, this guidance was largely based on evidence from studies conducted in resource-rich settings before the widespread use of ART.
In 2006, Kenya initiated a Food by Prescription (FBP) program in which eligible PLHIV (generally based on an assessment of their nutritional status) were prescribed specialized food products to treat severe to moderate undernutrition. The specialized food products were provided to the individuals in fixed portions (to discourage household sharing) until they reached “nutritional recovery” based on another nutritional assessment. This FBP model was later scaled up nationally in Kenya and now has been adapted by more than a dozen other countries supported by the US President's Emergency Plan for AIDS Relief (PEPFAR). In 2009, to limit the inclination of FBP programs to focus mainly on the specialized food products, PEPFAR began promoting the term “NACS” (nutrition assessment, counseling, and support) to encompass the entire spectrum of interventions needed to identify, prevent, and treat malnutrition (including both undernutrition and overnutrition). The extent of the implementation of NACS interventions and the impact on clinical outcomes remain unclear.
The aim of this systematic review was to evaluate the body of evidence on the effectiveness of NACS interventions among HIV-infected adolescents and adults in clinical care in low-resource settings. The review focuses on 5 outcomes, as mentioned in the introductory article14: mortality, morbidity, retention in care, quality of life, and ongoing HIV transmission. This article is 1 of 13 articles in this supplement addressing specific HIV care and support interventions.
Literature searches were conducted in 6 medical literature databases [MEDLINE, EMBASE, Global Health, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Sociological Abstracts (SOCA), and African Index Medicus (AIM)] to identify articles relevant to NACS interventions from January 1995 to May 2014. The overall search strategy is described in detail in the introduction to this supplement.14Table 1 shows the lists of intervention-specific search terms used for each database. Although unpublished studies, clinical trial registries or grey literature (e.g., government or organization reports) were not searched, one relevant unpublished report was identified by the United States Agency for International Development (USAID) and was included in this review.15
Study Selection and Eligibility Criteria
All abstracts identified through the literature search were screened independently by at least 2 investigators on the basis of predetermined eligibility criteria with a low threshold to exclude irrelevant abstracts. Full-text articles were retrieved for all abstracts that were deemed eligible by at least one investigator. Articles were then evaluated independently by teams of 2 investigators to determine whether they met the criteria for inclusion. Cases in which there was disagreement between the reviewers were resolved by discussion and consensus. Reference lists of all full-text articles were manually screened for additional publications.
We included studies in HIV-positive adolescents and adults (>14 years) in clinical care in low-resource settings. Included studies had to address a NACS intervention and report effects on at least 1 of the 5 designated outcomes (stated above). We operationalized the definition of nutrition support as either conventional food or macronutrient supplements. Macronutrient supplements included specialized food products such as ready-to-use supplementary or therapeutic foods (RUSF/RUTF) and fortified blended flours that require cooking [e.g., corn soya blend (CSB), CSB+, or high-energy protein supplements]. For the purpose of this review, we did not include studies of livelihood or household food security interventions. In addition, given the recently updated Cochrane review of micronutrient supplementation in children and adults with HIV,16 we excluded micronutrient interventions from this review as well. Recognizing the ethical complications of conducting randomized clinical trials (RCTs) of food support in malnourished populations living in resource-limited settings, we included other study designs such as cohort studies, quasi-experimental designs, and single-arm studies.
For the morbidity outcome, we included effects on CD4+ cell counts, hemoglobin concentration, number of severe clinical events (death or hospitalization), and WHO stage. For the outcome of retention in HIV care, we included effects on ART adherence, and for quality of life outcomes, we included Karnofsky score, measures of functional ability (physical, emotional, or social), and perceived health. Although some may consider HIV viral load as a morbidity outcome, we considered effects on viral load as an indicator of risk of HIV transmission given the importance of HIV treatment and viral load suppression as a method of HIV prevention. Full-text articles from abstracts focusing only on nutrition-related outcomes (e.g., change in weight or BMI) were also retrieved and reviewed for any relevant secondary outcomes analyzed that may not have been included in the abstract. On full review, articles that did not meet these eligibility criteria were excluded from further analysis.
Data Synthesis and Presentation
Study data from included articles were abstracted using a standardized data collection form to record key data elements, including study design, study period, number of participants, details of NACS intervention, and relevant outcomes assessed. Standardized criteria were used to assess internal validity of individual studies based on study design. For RCTs and cohort studies, the following criteria were used: initial assembly of comparable groups; clear definition of interventions; maintenance of comparable groups over follow-up period (includes attrition, crossovers, adherence, and contamination); differential loss to follow-up or overall loss to follow-up rate; measurements of outcomes being equal, reliable, and valid (includes masking of outcome assessment); and appropriate statistical analysis (e.g., adjustment for confounders in cohort studies or intention to treat analysis for RCTs). Single group designs (before and after comparisons, use of historical controls, implicit comparisons) were also included in this review, and separate criteria were used to assess internal validity for each single group design.17 For before and after comparisons, the following criteria were used: intervention was the only change across the time period; influence of adjunctive therapies or interventions administered concurrently; presence of carryover effects from therapies administered before the intervention of interest; possibility of natural recovery, reduction, or disappearance of symptoms; patients selected into the study represented a relatively extreme subset of the patient population with respect to disease severity and symptoms; and whether patients with more or less favorable outcomes were lost to follow-up. For single group studies that used historical controls, we judged internal validity based on the following criteria: changes or differences in factors other than intervention across time periods, availability of information on the variability of effect estimates from the historical control group, and adequacy of reporting of data sources for historical response rates.
Assessment of external validity was based on our judgment of how well the study population reflected the target population of HIV-positive adolescents and adults in clinical care in low-resource settings and if the study results could be generalized beyond each study's specific eligibility criteria. In addition, we abstracted information on the key findings for the relevant outcomes, timing of the intervention by WHO staging/CD4 count and ART status, and any information on cost effectiveness. For each individual study, the overall quality of evidence was rated as strong, medium, or weak based on the criteria described above and as described in the introductory article.14
Data from all eligible studies were then grouped according to outcome, and the quality of the entire body of evidence for that outcome was rated as good, fair, or poor, also as described in the introductory article.14 Finally, the expected impact of the intervention by outcome was rated as high, moderate, low, or uncertain based on the magnitude of effect demonstrated in individual studies, the quality of the body of evidence, and consistency across the studies.
Figure 1 displays the summary of our literature search and study selection process. The literature search yielded 2292 potentially relevant abstracts that were screened, resulting in a total of 60 studies that were considered for full-text retrieval. After reviewing the full texts, 39 were subsequently excluded because they did not meet the eligibility requirements stated above. The remaining 21 studies are included in this systematic review. Table S1 (see Supplemental Digital Content, http://links.lww.com/QAI/A641) summarizes the study design, sample size, key findings, and quality of evidence rating for each of these 21 studies.
There were 7 studies that examined the effect of an NACS intervention on mortality. Only 1 used a randomized design18; however, this trial did not have a control group. Instead, the comparison was between an RUSF and CSB. Mortality rates were high in both groups (26%–27%), and there was no difference in survival between the groups after 14 weeks. There were 2 cohort studies that compared mortality rates between PLHIV receiving a food supplement and PLHIV in communities that were not yet receiving food supplements due to a phased rollout of the food supplementation program. In one study, participants received a monthly ration of CSB, vegetable oil, maize meal, and beans,19 whereas in the other study, participants received an RUTF (Plumpy'Nut; Nutriset SAS, Malaunay, France).20 Neither study found a significant difference in mortality between those receiving food supplements and those who did not. The remaining 4 studies all used a single-arm design compared with historical controls. Three of these studies observed no difference in mortality rates,21–23 whereas the fourth study reported a significantly lower mortality rate for those on nutrition support (mortality ratio = 0.19, P < 0.05).24 Overall, we rated the body of evidence for mortality outcomes as “fair” and concluded that rolling out NACS will have an uncertain impact on mortality (see Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A641).
Change in CD4+ Cell Counts
We identified 12 studies that examined the impact of a NACS intervention on change in CD4+ cell count, which we considered to be a surrogate outcome for morbidity. Four of these studies were RCTs: 3 comparing one type of food supplement against another type of food supplement,18,25,26 and one unpublished report comparing 12 months of nutrition counseling alone to 12 months of nutrition counseling plus 6 months of food support (300 g/d of fortified blended flour).15 The results from these 4 trials were mixed. In a small study randomizing 26 PLHIV to spirulina (a blue-green alga with a very high protein content) and 26 PLHIV to soya beans, the authors reported that, on average, the spirulina group had a statistically significant larger increase in CD4+ cell counts than the soya bean group (+99 vs. +46 cells per cubic millimeter, P < 0.05).25 All participants initiated ART at the same time they were enrolled in the trial. In a Kenya Medical Research Institute (KEMRI) trial, participants were stratified by ART (n = 626) or pre-ART (n = 432) status.15 Although change in CD4+ counts did not differ between the food and no-food groups for those on ART, there was a small but statistically significant difference among those in the pre-ART strata. CD4+ counts increased by 7 cells per cubic millimeter in the food group, whereas it decreased by 33 cells per cubic millimeter in the no-food group (P = 0.04). The remaining 2 trials both found no difference in increase in CD4+ count when comparing an RUSF with either CSB or CSB+.18,26
There were 6 cohort studies examining the effect of a food supplement on change in CD4+ counts.19,20,27–30 Four of these found no effect.19,27,29,30 In a study conducted in India, Nyamathi et al28 reported that high-protein supplements plus intense support from accredited social health activists (ASHAs) resulted in significant improvements in CD4+ cell counts after 6 months compared with usual care. However, since the intervention group received weekly intense monitoring of ART adherence from ASHAs along with the high-protein supplements, the larger increase in CD4+ cell counts cannot be directly attributed to the effect of the protein supplement alone. In Ethiopia, Sadler et al20 found that participants at sites offering a food support program and prescribed Plumpy Nut showed an increase in CD4+ count of 75 cells per cubic millimeter more than participants at sites that did not offer the food support program, and this difference was most significant for those who were not on ART. However, pre- and post-CD4 data were only available for a small subset of participants in this study (21% of FBP group and 8% of control group). Overall, we rated the body of evidence for change in CD4 outcomes as “poor” and concluded that rolling out NACS will have an uncertain impact on CD4+ cell counts (see Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A641).
Other Morbidity Outcomes
Five studies included results on morbidity outcomes other than change in CD4+ counts. These outcomes included effects on hemoglobin concentrations,29,31 number of severe clinical events (including hospitalizations and death),23 change in WHO stage,24,32 and number of self-reported HIV-related symptoms.29 One of these studies was an RCT in Nigeria comparing 6 months of nutrition counseling with a control group who were not provided nutrition counseling. The authors reported a significantly higher hemoglobin concentration in participants who were assigned to monthly, individualized dietary and food hygiene counseling sessions compared with controls (12.1 vs. 11.2 mg/dL, P = 0.0015),31 suggesting that individualized counseling to improve intake of iron-rich foods that are locally available and affordable can help to improve or prevent HIV-related anemia. In Uganda, Rawat et al29 found no effect of food supplementation on hemoglobin concentrations in the overall cohort but reported a more significant impact among the subset of individuals with CD4 counts >350 cells per cubic millimeter. In the same study, Rawat et al found a significant reduction in the number of reported HIV-related symptoms in those receiving a food supplement compared with propensity score matched controls. In an earlier cohort, Rawat et al32 reported that participants not on ART and given household food rations were slightly less likely to progress to a worse WHO stage than propensity score matched controls, whereas there was no impact of food on WHO stage among those on ART. In the 2 single-arm studies, one found higher rates of clinical events (hospitalization or death) in those given an RUSF or CSB compared with historical controls,23 whereas the other found no difference in improvement in WHO stage among those given a family food ration compared with historical controls.24 Overall, we rated the body of evidence for other morbidity outcomes as “poor” and concluded that rolling out NACS will have an uncertain impact on morbidity (see Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A641).
Retention in Care
Seven studies examined the effect of food supplementation on adherence to ART, which was the only outcome related to retention in care that came up in the literature search. Most of these studies found that food supplementation had a positive impact on adherence as measured by medication possession ratio,19,33 pill counts,24,28 or clinic visit attendance.26 There were 2 RCTs in this group but neither found an effect on adherence.18,34 However, both trials were comparing RUSF versus CSB/CSB+ (i.e., neither trial had a no-food control group); therefore, it is not surprising that no differences in ART adherence were observed between the 2 trial arms. Overall, we rated the body of evidence for adherence outcomes as “fair” and concluded that rolling out NACS will have an uncertain impact on ART adherence (see Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A641).
Quality of Life
Seven studies examined the effect of food supplementation on quality of life. Two of these were single-arm studies with a before–after design,35,36 and both reported improvements in quality of life measures (ability to walk, Karnofsky score, and proportion “fully active”) from pre-RUTF to post-RUTF. The 2 RCTs of RUSF versus CSB/CSB+ also found improvements in quality of life in both study arms given food support.18,34 The RCT of 12 months of nutrition counseling plus food supplementation versus nutrition counseling alone in Kenya found a greater improvement in perceived health after 1 month of food supplementation in those who were pre-ART.15 However, this effect did not persist at later time points, nor was any effect observed among those on ART. The results from the 2 cohort studies were mixed. In Haiti, there was no effect of a food support program on quality of life after 12 months.26 In contrast, the cohort study in Ethiopia found that the food support group showed greater improvements in functional status compared with controls, although only a very small number of the original participants had this outcome assessed.20 Overall, we rated the body of evidence for this outcome as “fair” and concluded that rolling out NACS will have an uncertain impact on quality of life (see Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A641).
Prevention of HIV Transmission
Only 3 studies assessed the impact of food supplementation on the outcome of ongoing transmission, which we operationalized as HIV viral load levels. Two were RCTs comparing 2 types of food supplements,18,25 and the third was a single-arm before–after study.37 In all studies, ART was initiated at the same time as the food supplements so changes in viral load are difficult to interpret. Azabji-Kenfack et al found that participants randomized to a spirulina supplement had a significantly larger decrease in log viral load after 12 weeks compared with those randomized to soya beans. This was a small trial (n = 52) and therefore results should be replicated in a larger trial before firm conclusions can be made. Overall, we rated the body of evidence for this outcome as “poor” and concluded that rolling out NACS will have an uncertain impact on HIV viral load (see Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A641).
A 2007 Cochrane review examined the effects of macronutrient supplementation on morbidity and mortality in PLHIV and found no relevant clinical trials in low-resource settings.38 Our article updates this review of clinical trials and expands the scope to include other study designs that could inform our research question (e.g., cohort studies, quasi-experimental designs, and single-arm studies). We identified 21 articles, published between 2005 and 2014, reporting data on the clinical impact of a NACS intervention among PLHIV in resource-limited settings. Based on our review of the literature, we conclude that the data are inconclusive regarding the impact of NACS programming on all 5 outcomes of interest and that significant knowledge and research gaps remain.
Our review highlights the fact that the overall quality of evidence for the impact of NACS on clinical outcomes is extremely weak, predominantly due to the fact that very few studies were designed to directly address our questions of interest (Table 2). Although NACS encompasses the entire spectrum of nutritional interventions, all but one of the studies we reviewed evaluated only a single component of NACS, i.e., providing therapeutic and/or supplementary foods to those with severe to moderate undernutrition. Furthermore, within the realm of food support programs, very few of the studies were adequately designed to evaluate the effectiveness of food support on clinical outcomes in PLHIV.
Although RCTs would be the ideal study design to test the effectiveness of food support, they are difficult to conduct in resource-limited settings given the ethical considerations of randomizing nutritionally compromised individuals to a study arm that does not provide optimal nutrition services. Only 1 of the 4 studies we identified with randomized food support could directly address our questions of interest. This was the study by KEMRI, which compared nutrition counseling plus food support to nutrition counseling alone.15 The other RCTs compared one type of food support to another,18,25,34 and although most were well-conducted studies, the lack of a proper control group (one without food support) limits the ability to attribute any effects on outcomes to food support in general.
Several studies used a quasi-experimental (nonrandomized) prospective (cohort) study design, taking advantage of the common programmatic context in which food support programs are rolled out across a country in phases. These researchers were able to compare individuals living in districts/villages receiving food support with individuals living in districts/villages not yet receiving food support.19,20,29 Similarly, others conducted cohort studies comparing patients from clinics that distributed food support with patients from clinics (some within the same district) that did not distribute food support.30,33 This type of study assumes that clinics providing food support are similar to clinics not providing food support, an assumption that is oftentimes not met. The third type of cohort study design compared individuals within the same clinic or district who were eligible for food support to those who were not eligible for food support.26,27,32 This type of design, however, is somewhat weaker as those who are eligible for food support are likely to be sicker, more food insecure, and/or more nutritionally compromised at baseline compared to those who are not eligible for food support. Two of these studies accounted for this noncomparability of study groups by using propensity score matching, a method of statistical analysis that compares food support recipients with nonrecipients who most closely match their (measured) baseline characteristics,27,32 whereas the third study used traditional multivariate techniques to adjust for baseline differences. All of these designs and analytic strategies circumvent the ethical considerations of randomizing individuals to food versus no food, but they are still limited by their inability to adjust and control for unmeasured differences that are likely to exist between groups.
The third type of study design we encountered were those that used a single-arm design, either comparing outcomes before and after food intervention35–37 or comparing results with historical controls.21–23,37 Again, these types of study designs are far from ideal in that changes other than the intervention may occur during the intervention period (before/after design) or across time periods (historical controls). This makes it impossible to attribute findings to the effect of the intervention alone. However, these types of studies can be useful for generating hypotheses or demonstrating the feasibility and acceptability of an intervention.
In addition to study design, many of the studies we reviewed were further limited by the choice of populations in terms of disease stage and timing of intervention with respect to ART. For example, our review suggests that giving food to PLHIV is unlikely to have an impact on mortality. However, the studies evaluating mortality as an outcome enrolled populations that were either extremely advanced in their disease at the time of ART initiation or were stable on ART with therefore already low mortality rates. It would be difficult to expect NACS to provide a significant short-term survival advantage in either of these extreme circumstances. It may be more realistic to expect a survival advantage for PLHIV given food support at earlier stages of disease (before severe wasting) or to follow participants for a longer period after ART initiation.
In terms of morbidity, our review suggests no benefit of food supplementation on CD4 levels; however, many of the studies evaluated the effects of food support on changes in CD4 counts at the time of ART initiation or among subjects who were on ART for varying lengths of time. Since ART has such a strong and direct effect on CD4 counts at initiation, it is not surprising that additional benefits of food support are not observed during this stage of clinical care.
There is evidence from our review that food rations may help to improve ART adherence, although most of the studies used indirect measures of ART adherence such as clinic or pharmacy visits; therefore, it is not surprising that the promise of food motivated patients to attend their scheduled visits. What remains unknown is what happens to adherence between clinic visits, how long the promise of food will continue to be a motivating factor, and whether different types of food support could make a difference in adherence rates (i.e., whether a less palatable food supplement would have less effect on adherence).
Limited data are available examining the effect of food rations on ART adherence using the best measure of adherence, namely HIV viral load. Furthermore, the 3 studies examining the effect of food support on HIV viral load were difficult to interpret. In all 3, participants initiated ART at the same time they were given food support so it is impossible to distinguish the effects of ART versus food. Food support could provide PLHIV with nutrients essential for mounting an immune response to retard viral replication, but none of the studies were designed to determine the effects of food support on viral replication beyond the effects of ART.
Typically, approximately 10%–15% of adult patients entering clinical care and treatment require food support for an average of 3–5 months to achieve a BMI >18.5. Although providing FBP to these clinically undernourished patients remains a medical need per WHO guidance (irrespective of HIV status), the far greater scope of NACS lies in the long-term assessment and counseling of patients to manage their diets and lifestyles to tolerate and adhere to their medications, restore their immune response and health, and prevent the early onset of noncommunicable diseases. As stated earlier, none of the studies we reviewed evaluated a comprehensive NACS program. Given the expansion of ART eligibility criteria and the expected decline in proportions of adult PLHIV who will present with clinical wasting, the longer term effectiveness of nutrition assessment, counseling and other types of support, including economic strengthening, livelihood and food security support linked to adherence to clinical care and treatment, remains an important research gap. Although ART leads to initial weight recovery among those who are undernourished, many PLHIV on ART continue to gain weight with the belief that being heavier is healthier; but obesity can further elevate their risk for cardiovascular disease, stroke, and diabetes associated with HIV infection and chronic use of ARVs. Nutrition assessment and counseling could play an important role in the chronic care and treatment of PLHIV who now have life expectancies of decades, rather than months or years. Although nutrition assessment and counseling can be effective in improving energy intake, weight, and body composition,39 there is no evidence yet that it has any effect on long-term survival or other clinical/functional outcomes in PLHIV in resource-limited settings. Additional studies are needed to assess the effects of nutrition assessment and counseling over the short and longer term.
We identified only 1 study that focused on nutrition counseling as an intervention. This was the trial by Alo et al, which tested the effectiveness of monthly, individualized nutrition counseling in Nigeria. The authors found that hemoglobin concentrations, the only outcome of this study that was relevant to our review, were significantly higher among those who were counseled versus controls. While promising, this was a relatively small study (n = 84); therefore, results need to be replicated to include other clinical outcomes in larger populations before any firm conclusions can be drawn.
A scientific and data-driven approach to improve counseling techniques and modalities (e.g., individual vs group, frequency and duration of counseling, as well as the potential roles of different counselors including physicians, nurses, auxiliary and community health workers, and expert patients) is urgently needed to strengthen NACS, both at the level of the clinic and in the community. This would also include studies to develop and test nontraditional approaches to nutrition counseling that are less resource-intensive and replicable.
Programmatic Considerations for Implementation
NACS is a multisectoral, systems approach to integrating nutrition care within health services, linking clinics and communities, and embracing interventions that are nutrition-specific (those that address the immediate determinants of malnutrition) and nutrition-sensitive (those that address the underlying and systemic causes of malnutrition). NACS is a framework that provides opportunities to not only treat malnutrition but to prevent malnutrition across the continuum of care.
NACS also provides an important opportunity to connect patients in clinical care to economic strengthening and livelihood support to improve individual and household food security and resilience, which is a major concern among populations affected by HIV, particularly in low-resource settings. Thus, a successful model for nutrition counseling and other support in resource-limited settings could be more cost-effective, equitable, and sustainable in the long-term than traditional food support programs that focus solely on provision of specialized food products at the severe wasting end of the spectrum.
A number of issues pose challenges to effective implementation of NACS. Traditional methods of effective nutrition assessment and counseling can be complicated, as well as time- and resource-intensive. ART clinics are often understaffed, and the existing staff may feel unqualified or be unable to find the time to conduct proper nutrition assessment and provide adequate counseling to their clients, including counseling on adherence and retention in clinical care and treatment. The application of quality improvement approaches has been critical to finding efficiencies in service delivery, defining roles and responsibilities of staff, and establishing performance standards and supervision that allow integration of nutrition care within the clinical management of patients.
ART clinics also may not have the proper equipment or tools (e.g., scales and stadiometers) in working order to conduct nutrition assessments. Ministries of Health have been challenged to establish procurement, supply chain management and inventory control systems that can assure provision of appropriate therapeutic and supplementary foods to clinically malnourished adults and children. In addition, health systems are challenged to routinely and consistently provide micronutrient supplements for PLHIV whose diets are likely inadequate to meet vitamin and mineral requirements. Continued focus on quality improvement and strengthening procurement and supply chain systems will be key to assuring availability of necessary equipment and supplies.
The variable and largely poor quality of the studies we reviewed should not diminish concerns about nutrition status or the importance of NACS for PLHIV. There is an abundance of evidence that poor nutritional status at ART initiation is associated with increased mortality and other adverse outcomes. WHO, providing guidance on nutrition for adult PLHIV, underscores the importance of adequate nutrition, best achieved through consumption of a balanced healthy diet, as vital for health and survival for all individuals regardless of HIV status.13 By definition, essential nutrients are essential because of their established requirements for health, including immune function, which is significantly compromised by HIV infection. Studies addressing the need for food support among PLHIV should be appropriately designed to answer the questions of who should be prioritized to get the food, what the composition of the food should be, when they should get it, and for how long, particularly regarding early infection or as a long-term adjunct to ART to maintain nutritional status and improve clinical outcomes. In addition, as PLHIV are surviving longer, the impact of nutrition and the effectiveness of counseling to prevent or ameliorate noncommunicable diseases (heart disease, stroke, diabetes, osteoporosis, etc.) in resource-limited settings should also be at the forefront of research efforts.
The authors would like to thank Gail Bang and Emily Weyant for conducting the literature search for this review.
1. Liu E, Spiegelman D, Semu H, et al.. Nutritional status and mortality among HIV
-infected patients receiving antiretroviral therapy in Tanzania. J Infect Dis. 2011;204:282–290.
2. Calmy A, Pinoges L, Szumilin E, et al.. Generic fixed-dose combination antiretroviral treatment in resource-poor settings: multicentric observational cohort. AIDS. 2006;20:1163–1169.
3. Toure S, Kouadio B, Seyler C, et al.. Rapid scaling-up of antiretroviral therapy in 10,000 adults in Cote d'Ivoire: 2-year outcomes and determinants. AIDS. 2008;22:873–882.
4. Stringer JS, Zulu I, Levy J, et al.. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA. 2006;296:782–793.
5. Severe P, Leger P, Charles M, et al.. Antiretroviral therapy in a thousand patients with AIDS in Haiti. N Engl J Med. 2005;353:2325–2334.
6. Sieleunou I, Souleymanou M, Schonenberger AM, et al.. Determinants of survival in AIDS patients on antiretroviral therapy in a rural centre in the Far-North Province, Cameroon. Trop Med Int Health. 2009;14:36–43.
7. Marazzi MC, Liotta G, Germano P, et al.. Excessive early mortality in the first year of treatment in HIV
type 1-infected patients initiating antiretroviral therapy in resource-limited settings. AIDS Res Hum Retroviruses. 2008;24:555–560.
8. Zachariah R, Tayler-Smith K, Manzi M, et al.. Retention and attrition during the preparation phase and after start of antiretroviral treatment in Thyolo, Malawi, and Kibera, Kenya: implications for programmes? Trans R Soc Trop Med Hyg. 2011;105:421–430.
9. Srasuebkul P, Lim PL, Lee MP, et al.. Short-term clinical disease progression in HIV
-infected patients receiving combination antiretroviral therapy: results from the TREAT Asia HIV
observational database. Clin Infect Dis. 2009;48:940–950.
10. Barth RE, van der Meer JT, Hoepelman AI, et al.. Effectiveness of highly active antiretroviral therapy administered by general practitioners in rural South Africa. Eur J Clin Microbiol Infect Dis. 2008;27:977–984.
11. Koethe JR, Lukusa A, Giganti MJ, et al.. Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia. J Acquir Immune Defic Syndr. 2010;53:507–513.
12. Madec Y, Szumilin E, Genevier C, et al.. Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries. AIDS. 2009;23:853–861.
13. World Health Organization. Nutrient requirements for people living with HIV
/AIDS. Report of a technical consultation, Geneva, Switzerland, 13-15 May 2003.
14. Kaplan JE, Hamm TE, Forhan S, et al.. The impact of HIV
care and support interventions on key outcomes in low and Middle-Income countries: a literature review–introduction. J Acquir Immune Defic Syndr. 2015;68(suppl 3):S253–S256.
15. KEMRI. Randomized Controlled Trial of the Impacts of Supplementary Food on Malnourished Adult ART Clients and Adult Pre-ART Clients in Kenya, Final Report. 2012.
16. Irlam JH, Siegfried N, Visser ME, et al.. Micronutrient supplementation for children with HIV
infection. Cochrane Database Syst Rev. 2013;10:CD010666.
17. Ip S, Paulus JK, Balk EM, et al.. Role of Single Group Studies in Agency for Healthcare Research and Quality Comparative Effectiveness Reviews. Research White Paper. (Prepared by Tufts Evidence-based Practice Center under Contract No. 290-2007-10055-I). Rockville, MD: Agency for Healthcare Research and Quality; 2013.
18. Ndekha MJ, van Oosterhout JJ, Zijlstra EE, et al.. Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial. BMJ. 2009;338:b1867.
19. Cantrell RA, Sinkala M, Megazinni K, et al.. A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka, Zambia. J Acquir Immune Defic Syndr. 2008;49:190–195.
20. Sadler K, Bontrager E, Rogers B, et al.. Food by Prescription: Measuring the Impact and Cost-effectiveness of Prescribed Food on Recovery from Malnutrition and HIV
Disease Progression Among HIV
+ Adult Clients in Ethiopia. Boston,MA: Feinstein International Center, Friedman School of Nutrition
Science and Policy, Tufts University; 2012.
21. Bowie C, Kalilani L, Marsh R, et al.. An assessment of food supplementation to chronically sick patients receiving home based care in Bangwe, Malawi: a descriptive study. Nutr J. 2005;4:12.
22. Manary M, Ndekhat M, van Oosterhout JJ. Supplementary feeding in the care of the wasted HIV
infected patient. Malawi Med J. 2010;22:46–48.
23. van Oosterhout JJ, Ndekha M, Moore E, et al.. The benefit of supplementary feeding for wasted Malawian adults initiating ART. AIDS Care. 2010;22:737–742.
24. Serrano C, Laporte R, Ide M, et al.. Family nutritional support improves survival, immune restoration and adherence in HIV
patients receiving ART in developing country. Asia Pac J Clin Nutr. 2010;19:68–75.
25. Azabji-Kenfack M, Dikosso SE, Loni EG, et al.. Potential of spirulina platensis as a nutritional supplement in malnourished HIV
-infected adults in Sub-Saharan Africa: a randomised, single-blind study. Nutr Metab Insights. 2011;4:29–37.
26. Ivers LC, Chang Y, Gregory Jerome J, et al.. Food assistance is associated with improved body mass index, food security and attendance at clinic in an HIV
program in central Haiti: a prospective observational cohort study. AIDS Res Ther. 2010;7:33.
27. Chakravarty S. Harvesting Health: Fertilizer, Nutrition
and AIDS Treatment in Kenya. New York, NY: Graduate School of Arts and Sciences, Columbia University; 2009.
28. Nyamathi A, Sinha S, Ganguly KK, et al.. Impact of protein supplementation and care and support on body composition and CD4 count among HIV
-infected women living in rural India: results from a randomized pilot clinical trial. AIDS Behav. 2013;17:2011–2021.
29. Rawat R, Faust E, Maluccio JA, Kadiyala S. The impact of a food assistance program on nutritional status, disease progression, and food security among people living with HIV
in Uganda. J Acquir Immune Defic Syndr. 2014;66:e15–22.
30. Swaminathan S, Padmapriyadarsini C, Yoojin L, et al.. Nutritional supplementation in HIV
-infected individuals in South India: a prospective interventional study. Clin Infect Dis. 2010;51:51–57.
31. Alo C, Ogbonnaya LU, Azuogu BN. Effects of nutrition counseling
and monitoring on the weight and hemoglobin of patients receiving antiretroviral therapy in Ebonyi State, Southeast Nigeria. HIV
AIDS (Auckl). 2014;6:91–97.
32. Rawat R, Kadiyala S, McNamara PE. The impact of food assistance on weight gain and disease progression among HIV
-infected individuals accessing AIDS care and treatment services in Uganda. BMC Public Health. 2010;10:316.
33. Tirivayi N, Koethe JR, Groot W. Clinic-based food assistance is associated with increased medication adherence among HIV
-infected adults on long-term antiretroviral therapy in Zambia. J AIDS Clin Res. 2012;3:171.
34. Ivers LC, Teng JE, Jerome JG, et al.. A randomized trial of ready-to-use supplementary food versus corn-soy blend plus as food rations for HIV
-infected adults on antiretroviral therapy in rural Haiti. Clin Infect Dis. 2014;58:1176–1184.
35. Bahwere P, Sadler K, Collins S. Acceptability and effectiveness of chickpea sesame-based ready-to-use therapeutic food in malnourished HIV
-positive adults. Patient Prefer Adherence. 2009;3:67–75.
36. Greenaway KA, Jere EC, Zimba ME, et al.. Examining the integration of food by prescription into HIV
care and treatment in Zambia. Emerg Nutr Netw Field Exchange. 2012:30–31. Available at: http://fex.ennonline.net/42/examining
. Accessed February 4, 2015.
37. Scarcella P, Buonomo E, Zimba I, et al.. The impact of integrating food supplementation, nutritional education and HAART (Highly Active Antiretroviral Therapy) on the nutritional status of patients living with HIV
/AIDS in Mozambique: results from the DREAM Programme. Ig Sanita Pubbl. 2011;67:41–52.
38. Mahlungulu S, Grobler LA, Visser ME, et al.. Nutritional interventions for reducing morbidity and mortality in people with HIV
. Cochrane Database Syst Rev. 2007:CD004536.
39. Baldwin C, Weekes CE. Dietary advice with or without oral nutritional supplements for disease-related malnutrition in adults. Cochrane Database Syst Rev. 2011:CD002008.
nutrition; nutrition assessment; nutrition counseling; food supplement; HIV; systematic review
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