Mark Manary

Supplementary and Supplementary and Therapeutic Feeding in Therapeutic Feeding in Adults Living with HIVAdults Living with HIV Mark J Manary MD

Washington University School of Medicine and Medical College of Malawi

Global Harvest Alliance

Why might food be given to Why might food be given to peoplepeople with HIV? with HIV?• To treat adult malnutrition – individuals with

low body mass index may benefit from special diets

• To treat micronutrient deficiency – which may slow disease progression either before or after onset of ART

• To promote general welfare among a vulnerable group of people

Treatment of malnutrition Treatment of malnutrition in HIV infected people in HIV infected people • Primary cause of weight loss in HIV patients thought to be

anorexia caused by elevated inflammatory cytokines, IL-1, IL-6, and TNF-α .

• A 2005 World Health Organization review recommended that daily energy intake should be increased by 10% for patients with asymptomatic HIV infection and by 20%-50% for patients recovering from opportunistic infections

• Low BMI at the start of ART is an independent predictor of early mortality in several analyses from sub-Saharan Africa

• Early evidence suggests that food supplementation programs

can help to improve patient retention and ART adherence.

Randomized Controlled Trial of the Impacts of Randomized Controlled Trial of the Impacts of Supplementary Food on Malnourished Adult ART Supplementary Food on Malnourished Adult ART Clients and Adult pre-ART Clients in KenyaClients and Adult pre-ART Clients in KenyaKenya Medical Research Institute (KEMRI) and the Food and Nutrition Technical Assistance (FANTA) Project at the Academy

for Educational Development (AED) Report June 2011.

• Randomized controlled trial evaluated the impact of six months of supplementary food on nutritional and clinical outcomes for two groups: Adult PLHIV with BMI < 18.5 kg/m2 scheduled to begin ART within 5 weeks of recruitment and malnourished and nutritionally vulnerable HIV-infected adults not eligible for ART.

• Evaluated the impact of supplementary food on nutritional and clinical status, treatment progress, and quality of life

• Subjects were randomized to receive nutrition counseling and 1350 kcal /day from fortified blended food or nutrition counseling alone, in addition to standard care

Kenya FindingsKenya Findings• Among Pre-ART patients

– Group who received food achieved significantly greater increases in body mass index (BMI) and hemoglobin levels during the six months of food supplementation than patients who did not receive food.

– CD4 counts of group receiving supplementary food increased modestly while CD4 counts of their peers who were not receiving food declined—effect statistically significant at three months but not at six or twelve months

• Among patients on ART– food supplementation led to significantly greater improvements in nutritional

status through three months, but not beyond– CD4 counts of ART clients increased significantly, but there were no significant

differences between the food and no-food groups in CD4 counts• Food supplementation increased clinic attendance among both pre-ART and ART

clients• Findings suggest that food supplementation delivered in clinical settings can

confer significant benefits to malnourished and nutritionally vulnerable adult PLHIV, especially pre-ART clients.

Supplementary feeding with either ready-to-use fortified Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trialblinded, controlled trialNdekha MJ 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 May 22;338:b1867. doi: 10.1136/bmj.b1867.

• Randomized investigator blind controlled trial investigated effect of two different nutritional supplements on the BMI of wasted adults with HIV who were starting ART.

• Study took place at the antiretroviral therapy clinic of Queen Elizabeth Central Hospital in Blantyre, Malawi, from January 2006 to April 2007

• 491 patients enrolled and randomized to receive either a fortified spread of corn soy blend.

• Primary outcomes were changes in BMI and fat-free body mass after 14 weeks. Secondary outcomes were nutritional status, quality of life, serum albumin concentration, hemoglobin concentration, CD4 count, HIV viral load, and adherence to antiretroviral therapy

Malawi FindingsMalawi Findings• Mean BMI at enrollment was 16.5• Patients in the fortified spread group had a greater

increase in BMI and fat-free body mass than those in the corn soy group at 14 wks.

• The mortality rate was 27% for those receiving fortified spread and 26% for those receiving corn-soy blend. No significant differences in the CD4 count, HIV viral load, assessment of quality of life, or adherence to antiretroviral therapy were noted between the two groups.

A Pilot Study of Food Supplementation to Improve A Pilot Study of Food Supplementation to Improve Adherence to Antiretroviral Therapy Among Food-Adherence to Antiretroviral Therapy Among Food-Insecure Adults in Lusaka, ZambiaInsecure Adults in Lusaka, ZambiaCantrell RA, 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 Oct 1;49(2):190-5.

• Analysis comparing adherence (assessed by medication possession ratio), CD4, and weight gain outcomes among HIV patients receiving food supplementation with those enrolled at the control clinics not receiving food.

• 636 food- insecure adults initiating ART and enrolled in in the voluntary home-based adherence support program were included in analysis

• Four clinics provided food supplementation, and 4 acted as controls

Zambia FindingsZambia Findings• Food supplementation was associated with better

adherence to therapy. Two hundred fifty-eight of 366 (70%) patients in the food group achieved a medication possession ratio of 95% or greater versus 79 of 166 (48%) among controls

• Significant differences were not found for weight gain or CD4 cell response in between the control and food supplementation groups

Nutritional Supplementation in HIV-InfectedNutritional Supplementation in HIV-InfectedIndividuals in South India: A ProspectiveIndividuals in South India: A ProspectiveInterventional StudyInterventional StudySwaminathan S,et al. Nutritional supplementation in HIV-infected individuals in South India: a prospective interventional

study. Clin Infect Dis. 2010 Jul 1;51(1):51-7.

• Prospective interventional study of 636 ART-naïve HIV-infected adults attending Tuberculosis Research Centre clinics in South India from June 2005 through December 2007

• Patients at all clinics received nutritional counseling and standard care, patients at 2 clinics also received macronutrient providing 400 cal and 15 g of protein daily.– The high-calorie, high-protein macronutrient supplement

Indiamix, which was provided by the World Food Program in India, is a blended, fortified mixture of whole wheat and soya bean flour fortified with vitamins A, B1, B2, B12, and C as well as niacin and folic acid but no iron.

• Study outcomes included changes in weight, BMI, body composition and immune status (CD4 cell count) at 6 months.

Indian FindingsIndian Findings• A total of 10% of patients died, and 30% discontinued

participation in the study for various reasons, such as distaste for food, nausea, early satiety, inability to cook, and/or embarrassment regarding carrying the supplement home. A total of 361 patients completed 6 months of supplementation

• 36% of men and 30% of women were severely malnourished, with a BMI <18.5 at baseline.

• Significant increases in body weight, BMI, MUAC, fat-free mass, and body cell mass were observed in the supplement group but not in the control group at 6 months; gains were greater in patients with CD4 cell counts < 200 cells/mL

• Macronutrient supplementation did not result in significantly increased weight compared with standard care.

The Impact of Food Assistance on Weight Gain andThe Impact of Food Assistance on Weight Gain andDisease Progression among HIV-InfectedDisease Progression among HIV-InfectedIndividuals Accessing AIDS Care and TreatmentIndividuals Accessing AIDS Care and TreatmentServices in UgandaServices in UgandaRawat R et al. 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 Jun 7;10:316.

• Data from The AIDS Support Organization (TASO) in Uganda analyzed to compare outcomes among food assistance (FA) recipients to a control group among 14,481 HIV-infected clients.

• Estimated the impact of FA using propensity score matching with difference-in-difference (DID) estimates. This statistical procedure compares the change over time in the outcomes of interest for FA TASO clients with the change over time to matched comparison TASO clients.

• Estimated the overall and conditional effects of FA on weight and disease progression by one or more WHO stages

Ugandan FindingsUgandan Findings• Final sample for analysis included 14, 481 observations, 23%

of whom reported receiving food assistance• FA resulted in a significant mean weight gain over one year

period. Impact was conditional on anti-retroviral therapy (ART) receipt and disease stage at baseline.

• FA resulted in mean weight gain of 0.36 kg among individuals not receiving ART compared to their matched controls..

• Individuals with the most advanced disease at baseline (WHO stage IV) had the highest weight gain of 1.9 kg.

• Impact of FA on disease progression was minimal. Individuals receiving FA were 2% less likely to progress by one or more WHO stage compared to their matched controls in 1 year

• There were no significant impacts on either outcome (weight gain or disease progression) among individuals receiving ART.

A Randomized Trial of Multivitamin Supplements A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortalityand HIV Disease Progression and MortalityFawzi WW, et al. A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality. N Engl J Med.

2004 Jul 1;351(1):23-32.

• Double-blind, placebo-controlled trial in Dar es Salaam, Tanzania to examine effects of daily supplements of vitamin A (preformed vitamin A and beta carotene), multivitamins (vitamins B, C, and E), or both on progression of HIV disease

• 1078 HIV-infected pregnant women enrolled• Primary aims were to compare the effects of multivitamins, vitamin A

alone, and both with those of placebo.• Compared effects of the supplements on T-cell counts (CD4+, CD8+, and

CD3+), viral load, and individual signs of disease, including conditions ascertained by study physicians at clinic visits, such as thrush, gingival erythema, angular cheilitis, oral ulcers, and acute upper respiratory tract infection.

Tanzanian FindingsTanzanian Findings• 24.7 percent of women who received multivitamins had

progression to World Health Organization (WHO) stage 4 disease or died as compared to 31.1 percent who received placebo (P=0.04)

• Multivitamin regimen was also associated with reductions in the relative risk of death related to the acquired immunodeficiency syndrome, progression to WHO stage 4,or progression to stage 3 or higher.

• Those in the multivitamin group also had significantly higher CD4+ and CD8+ cell counts and significantly lower viral loads.

• Group that received vitamin A alone did not have significantly different results than those that received placebo.

Micronutrient Supplementation Increases CD4 Count in HIV-Micronutrient Supplementation Increases CD4 Count in HIV-Infected Individuals on Highly Active Antiretroviral Therapy: Infected Individuals on Highly Active Antiretroviral Therapy: A Prospective, Double-Blinded, Placebo-Controlled TrialA Prospective, Double-Blinded, Placebo-Controlled TrialKaiser, JD. Micronutrient Supplementation Increases CD4 Count in HIV-Infected Individuals on Highly Active Antiretroviral

Therapy: A Prospective, Double-Blinded, Placebo-Controlled Trial. J Acquir Immune Defic Syndr. 2006 Aug 15;42(5):523-8.

• A prospective, randomized, double-blinded, placebo-controlled trial to examine immunologic, metabolic, and clinical effects of broad spectrum micronutrient supplementation in HIV-infected patients taking highly active antiretroviral therapy (HAART).

• 40 HIV-infected patients taking a stavudine and/or didanosine-based HAART regimen were randomized to receive micronutrients or placebo twice daily for 12 weeks

• Patients had a laboratory-monitoring panel, a clinical assessment, and a neurological examination every four weeks

FindingsFindings• The mean absolute CD4 count increased by an average of 65

cells in the micronutrient group versus a 6-cell decline in the placebo group at 12 weeks (P = 0.029)

• The absolute CD4 count increased by an average of 24% in the micronutrient group versus a 0% change in the placebo group (P = 0.01).

• Neuropathy scores improved in the micronutrient group by 42% compared with a 33% improvement in the placebo group—not statistically significant.

• Fasting serum glucose, insulin, and lipids were not adversely affected in the patients taking the micronutrients.

Food Assistance is Associated with ImprovedFood Assistance is Associated with ImprovedBody Mass Index, Food Security And AttendanceBody Mass Index, Food Security And AttendanceAt Clinic in an HIV Program in Central Haiti:At Clinic in an HIV Program in Central Haiti:A Prospective Observational Cohort StudyA Prospective Observational Cohort StudyIvers LC, 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 Aug 26;7:33.

• Prospective observational cohort study of 600 people living with HIV enrolled in HIV care in Partners In Health (PIH) programs in rural Haiti.

• Adults received twelve months of food assistance (FA) if they had HIV and any one of: co-infection with active TB, CD4 count less than 350 cells/mm3 in the prior three months, BMI less than 18.5 or severe socioeconomic circumstances– Ration consisted of 50 gm of cereal, 50 gm of dried legumes, 25 gm of

vegetable oil, 100 gm of corn-soya blend and 5 gm of iodized salt for each of 3 family members (approximately 949 kilocalories) per person per day.

• 300 eligible and 300 ineligible for FA were interviewed before rations were distributed, at 6 months and at 12 months. Data collected included demographics, BMI and food insecurity score (range 0 - 20).

• Multivariable analysis, linear regression and repeated measures logistic regression analysis were,used to compare the change from baseline between the two groups (FA and no FA) controlling for other factors

Haitian FindingsHaitian Findings• At 6 months, food security significantly improved in those

who received FA compared to those who did not (-3.55 vs -0.16; P < 0.0001)

• BMI decreased significantly less in the FA group than in the non-food assistance group (-0.20 vs -0.66; P = 0.020).

• At 12 months, FA was associated with improved food security (-3.49 vs -1.89, P = 0.011) and BMI (0.22 vs -0.67, P = 0.036).

• FA associated with improved adherence to monthly clinic visits at both 6 (P < 0.001) and 12 months (P = 0.033).

• Among those on ART, at 6 months, those receiving FA reported fewer difficulties taking their medications (14.4% vs. 28.1%, P = 0.001). At 12 months, this difference was no longer statistically significant .

Health and welfare effects of integrating AIDS Health and welfare effects of integrating AIDS treatment with food assistance in resource treatment with food assistance in resource constrained settings: A systematic review of theory constrained settings: A systematic review of theory and evidenceand evidenceTirivayi N, et al. Health and welfare effects of integrating AIDS treatment with food assistance in resource constrained settings:

A systematic review of theory and evidence. Soc Sci Med. 2011 Sep;73(5):685-92. Epub 2011 Jul 23.

• Systematic review of theory and evidence on the health and welfare effect of including food assistance with AIDS treatment

• PubMed, MEDLINE, Cochrane database of systematic reviews, Social Science Research Network, Economic Papers, Science Direct and the Google search engine used to conduct search from October 2009-August 2010.

• Studies had to meet the following inclusion criteria: – 1) Randomized controlled trials, case control studies or quasi-experimental studies. – 2) Descriptive or qualitative. – 3) Setting of the study is in resource constrained settings (developing countries). – 4) Focused on non-pregnant adult individuals. – 5) Assessed outcomes for ART patients and their households. – 6) Compared outcomes of food assistance recipients to non-recipients

• After screening, five studies were identified and included in the review

Welfare FindingsWelfare Findings• One study found a positive association between food

assistance and adherence to ART• Little evidence on welfare outcomes– Byron et al. (2008) found that patients reported

resumption of labor activities, increased dietary diversity and food consumption, food rations being shared within the household with preferential allocation to the AIDS patient.

• Further research with strong study designs needed to investigate health and welfare effects of integrating AIDS assistance with food assistance.