1. Supplementary and
Supplementary and
Therapeutic Feeding in
Therapeutic Feeding in
Adults Living with HIV
Adults Living with HIV
Mark J Manary MD
Washington University School of Medicine and Medical
College of Malawi
Global Harvest Alliance

3. people with HIV?
people
Why might food be given to
• 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

4. 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.

5. 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 Kenya
Clients and Adult pre-ART Clients in Kenya
Kenya 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

6. Kenya Findings
Kenya 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.

7. 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 trial
blinded, controlled trial
Ndekha 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

8. Malawi Findings
Malawi 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.

9. 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, Zambia
Insecure Adults in Lusaka, Zambia
Cantrell 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

10. Zambia Findings
Zambia 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

11. Nutritional Supplementation in HIV-Infected
Nutritional Supplementation in HIV-Infected
Individuals in South India: A Prospective
Individuals in South India: A Prospective
Interventional Study
Interventional Study
Swaminathan 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.

12. Indian Findings
Indian 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.

13. The Impact of Food Assistance on Weight Gain and
The Impact of Food Assistance on Weight Gain and
Disease Progression among HIV-Infected
Disease Progression among HIV-Infected
Individuals Accessing AIDS Care and Treatment
Individuals Accessing AIDS Care and Treatment
Services in Uganda
Services in Uganda
Rawat 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

14. Ugandan Findings
Ugandan 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.

15. A Randomized Trial of Multivitamin Supplements
A Randomized Trial of Multivitamin Supplements
and HIV Disease Progression and Mortality
and HIV Disease Progression and Mortality
Fawzi 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.

16. Tanzanian Findings
Tanzanian 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.

17. 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 Trial
A Prospective, Double-Blinded, Placebo-Controlled Trial
Kaiser, 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

18. Findings
Findings
• 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.

19. Food Assistance is Associated with Improved
Food Assistance is Associated with Improved
Body Mass Index, Food Security And Attendance
Body Mass Index, Food Security And Attendance
At Clinic in an HIV Program in Central Haiti:
At Clinic in an HIV Program in Central Haiti:
A Prospective Observational Cohort Study
A Prospective Observational Cohort Study
Ivers 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

20. Haitian Findings
Haitian 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 .

21. 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 evidence
and evidence
Tirivayi 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

22. Welfare Findings
Welfare 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.