1. Getting the Knack of NACS:
Nutrition Implications of HIV and ART
Alice Tang, Ph.D.
Tufts School of Medicine
Washington, DC
February 22-23, 2012

2. Learning Objectives
Review of scientific evidence:
1. To understand interactions between nutrition
and HIV
2. To understand the nutrition implications of ART

3. Outline
 Nutrition research prior to ART
 Nutrition research post-ART rollout
How do nutritional status and food insecurity affect:
• PLWHA at uptake/initiation of ART,
• PLWHA on ART (adherence), and
• Patient outcomes on ART (measured by indices
such as CD4 count, viral load, and mortality)

4. HIV – Nutrition Spiral
Insufficient dietary intake
Malabsorption and diarrhea
Impaired storage and altered metabolism
Malnutrition:
HIV Infection Protein-energy malnutrition
Micronutrient deficiencies
Nutritionally acquired immunodeficiency

5. Etiology of Malnutrition
in HIV infection
 Decreased Dietary Intake:
• Food
insecurity, depression, anxiety, anorexia, physical
symptoms that impair intake (oral
lesions, bloating, diarrhea, constipation)
 Malabsorption of micro- and macro- nutrients
• Antibiotic effects on intestinal flora, HIV-induced
mucosal changes, ARV effects, gastrointestinal
infections
 Altered Metabolism:
• Fever or inflammatory effects on basal metabolic
rate, hormonal deficiencies, ARV effects

6. Pre-ART: Focus on weight loss and
micronutrient deficiencies
 Weight loss and low micronutrient levels
associated with increased progression of disease
 Death associated with weight less than 66% of
ideal body weight
 Death associated with lean body mass falling below
54%
 As little as 3-5% weight loss associated with
mortality
Kotler, 1989; Chlebowski, 1989; Guenter, 1993; Palenicek,
1995; Wheeler,1996; Jones, 2003; Tang, 2005

7. 2003 World Health Organization
Dietary Recommendations for HIV
 Energy Requirements to maintain weight
• Increase by ~10% in asymptomatic HIV
• Increase by 20-30% in symptomatic HIV/AIDS
 Protein Requirements
• No evidence exists for increased needs
• ~10% increase with OI
 Micronutrient Requirements
• No evidence to support taking supplements
above DRI

8. Post-ART rollout:
How does Nutritional Status affect
ART outcomes?

9. What we know…
 Low BMI at ART initiation is associated with
increased mortality
 ART initiation is associated with weight gain
 Early weight gain on ART is associated with
survival, particularly when baseline BMI is low.

10. Baseline nutritional status predicts
ART survival
Author, Year Country N Mortality Predictors of Mortality
Severe, 2005 Haiti 1004 10% (6M) AIDS-defining illness, CD4≤50 cells/µl, low weight
13% (12M) (lowest quartile for sex)
Ferradini, 2006 Chiradzulu 1266 19% (8M) BMI<18.5, WHO stage IV, male sex, and baseline
district, Malawi CD4<50
Paton, 2006 Singapore 394 20% (29M) BMI<17, WHO Stage, non-HAART
Zachariah, 2006 Thyolo district, 1507 8% (3M) WHO stage IV, CD4≤50 cells/µl, and BMI<16 kg/m2
Malawi 13% (24M)
Stringer, 2006 Lusaka, Zambia 16,198 5% (3M) CD4 count, WHO stage, BMI<16 kg/m2, severe
anemia, and poor adherence to ART.
Calmy, 2006 11 countries 6861 7% (6M) Male gender, WHO stages III & IV, BMI<18 kg/m2,
(Africa, Asia, 10% (12M) CD4<15 cells/µl, Hgb<100 g/l.
Central America)
Erikstrup, 2007 Zimbabwe 196 HIV RNA level, HB, CD4 cell count, and CDC category
Barth, 2008 Elandsdoorn, 675 19% (12M) Karnofsky score ≤50, CD4<50
South Africa
Johannessen, 2008 Tanzania 320 18% (3M) Moderate/severe anemia, thrombocytopenia, and
30% (11M) BMI<16 kg/m2
Marazzi, 2008 Mozambique, 3456 53% (6M) BMI <18.0 kg/m2, Hgb, clinical staging, viral load,
Tanzania, Malawi and CD4 cell counts
Toure, 2008 Cote d’Ivoire, 10 211 15% (18M) Male gender, Age, CD4<150, WHO stages 3 and 4,
West Africa Hgb, BMI<18.5, type of care center
Srasuebkul, 2009 17 clinics in Asia- 1663 29% (20M) BMI≤18, mild to severe anemia, CD4≤200, age≤29
Pacific region

11. Koethe et al. JAIDS 2010

12. What we know…
 Low BMI at ART initiation is associated with
increased mortality
 ART initiation is associated with weight gain
 Early weight gain on ART is associated with
survival, particularly when baseline BMI is low.
[Madec, 2009; Olawumi, 2008; Ross-Degnan, 2010;
Saghayam, 2007; Tang, 2011]

13. ART initiation is associated
with weight gain
BMI<=17
BMI: >17 to <=18.5
BMI: >18.5 to <=20
BMI: >20
Madec et al, AIDS 2009

14. ART initiation is associated
with weight gain
BMI<=17
BMI: >17 to <=18.5
BMI: >18.5 to <=20
BMI: >20
Madec et al, AIDS 2009

15. What we know…
 Low BMI at ART initiation is associated with
increased mortality
 ART initiation is associated with weight gain
 Early weight gain on ART is associated with
survival, particularly when baseline BMI is low.

16. Baseline BMI and 6 month weight gain as a predictor of mortality
BMI<16.0 BMI 16.00-16.99
BMI>18.5
BMI 17.00-18.49
Koethe et al. JAIDS 2010

17. BMI and weight gain at M3* increases
mortality during 3-6 month period
* M3 = 3 months on ART
Madec et al, AIDS 2009

18. BMI and weight gain at M6* increases
mortality during 6-12 month period
*M6 = 6 months on ART
Madec et al, AIDS 2009

19. BMI and CD4 response
 No association between BMI and magnitude of
CD4 recovery
 CD4 response appears to modify the
association between BMI and mortality
• Low BMI and attenuated CD4 response (≤99
cells/mm3 increase or CD4 decline) is a
strong predictor of mortality.

20. BMI and CD4 response
Author, Year Country N BMI predicts CD4 response?
Paton, 2006 Singapore 394 No
Barth, 2008 Elandsdoorn, 675 Yes (BMI<17.1)
South Africa
Toure, 2008 Cote d’Ivoire, 10 211 No
West Africa
Koethe, AIDS, Lusaka, 56,612 Yes, but not clinically
2010 Zambia significant
Kiefer, 2011 Rwanda 537 F No
Tang Vietnam 100 M No
(Unpublished)

21. Koethe et al, AIDS 2010

22. BMI and CD4 response
 No association between BMI and magnitude of
CD4 recovery
 CD4 response appears to modify the
association between BMI and mortality
• Low BMI and attenuated CD4 response (≤99
cells/mm3 increase or CD4 decline) is a
strong predictor of mortality.

23. Adjusted hazard ratios of death, by
baseline BMI and CD4 change
6 months on ART Koethe et al, AIDS 2010

24. Knowledge Gaps
 What we know so far…
• Baseline nutritional status (BMI) predicts ART survival
• Weight changes appear to parallel the success of ART
• Weight and CD4 gains on ART associated with lower
risk of death
 What we don’t know…
 Will interventions to improve weight (BMI) prior to or at
ART initiation improve subsequent outcomes?
 Are baseline BMI and weight gain just a marker for
disease severity?
 Issues of timing – nutritional support and ART

25. How does Food Insecurity affect
ART outcomes?

26. What is Food Insecurity?
 Household level: Lack of access for all members at
all times to enough food to lead active, healthy
lives.
 Individual level: Inability to meet food needs at all
times in socially acceptable ways.
 Food insecurity leads to worse health outcomes
across a range of diseases (heart disease,
diabetes, obesity, and depression) [Seligman 2007;
Seligman 2010]

27. HIV and Food Insecurity:
What do we know?
 High prevalence of food insecurity in HIV infected
populations (nearly half of HIV+ urban poor) (Normen
2005; Kalichman 2010; Anema 2011; McMahon 2011)
 Globally, inadequate access to food and safe water can
be a barrier to ART uptake and adherence (Weiser 2010;
Chakrapani 2008; Franke 2010; Kalichman 2011; Nagata 2011)
 Food insecurity associated with incomplete viral
suppression, reduced CD4 response, and increased
mortality (Weiser 2008; Wang 2011; Kalichman 2010; McMahon
2011; Weiser 2009)
 See review articles by Weiser et al. 2011, Anema et al.
2009, and Ivers et al. 2009.

28. Food insecurity is a barrier to ART
uptake and adherence
 Reviewed by Bartlett, 2009 and Vervoort, 2007
 Food insecurity barriers:
• 76% feared developing too much appetite on ART but
not having enough to eat [Au, 2006].
• ART costs (e.g. transportation, registration and user
fees, and lost wages due to long waiting times)
undermine family welfare [Crane, 2006; Hardon, 2007].
• Long-term lifestyle changes: avoiding all alcohol and
smoking, eating sufficient quantities of food regularly,
and always having sex with condoms [Murray, 2009].
• Increased hunger, worse ARV side-effects w/o food,
counseling on need for food with ART, competing
demands between food and health care expenses,
forgetting to take ARV’s when working or searching for
food [Weiser, 2010].

29. Barriers to free ART for injecting
drug users (IDU) in India
 Lack of access to adequate/nutritious food
prevents IDUs from start taking ART
• They [IDUs] become afraid as they [counselor/doctor]
say that there would be side-effects.
• We are asked to take good food but we don‟t even have
food at times.
• We are afraid that something might happen if we take
[ART] without taking food.‟
Chakrapani, V., Velayudham, J., Michael, S., Shanmugam, M. (2008).
Barriers to free antiretroviral treatment access for injecting drug users in
Chennai, India. Indian Network for People living with HIV and AIDS
(INP+), Chennai, India.

30. Barriers to free ART for injecting
drug users (IDU) in India
 For homeless IDU getting food (and drugs) would
be a priority – not taking ART
• „He is on the roads [homeless IDU]. What will he do if
he is given ART? He doesn‟t have food to eat.
• For him [getting] food is more important than ART.
Chakrapani, 2008

31. Barriers to free ART for injecting
drug users (IDU) in India
 Food menu offered by counselors is “Only for
rich”
• Can the one on platform [homeless] drink hot
water? Can he take nutritious food such as nuts,
dates, dal? He would just nod his head to the
counselor while all these questions keep flashing in
his mind. He doesn‟t get admitted - neither does he
get ART. He thinks, “Oh! There is so much in this
[taking ART]. So let me continue doing whatever I
am doing now and die when I am going to”.‟
Chakrapani, 2008

32. HIV
• Loss of income • Stigma
• Loss of labor (farming) • Isolation
• Cost of ART ($ and time) • Depression
Food Insecurity
Physical: Psychosocial: Depression, Worry,
Under- (or over) nutrition Anxiety, Fear of Hunger, Stigma
Reduced Health and Function:
Malnutrition – exacerbates HIV
Adverse family and social interactions
Substance Abuse
Increased HIV risk behaviors
Inability to initiate/tolerate/adhere to ART
Ivers, 2009; Frega, 2010;Weiser, 2011;

33. HIV and nutrition nexus – which
approach should NACS programs take?
 Address direct biological effect of nutrition status
on HIV disease progression
• Increase energy intake
• Increase protein intake
• Micronutrient repletion
 Address social determinants of food insecurity
and barriers to adherence.

34. HIV and nutrition nexus – which
approach should NACS programs take?
Low BMI
Early mortality
on ART
Food
Insecurity Poor CD4 response,
incomplete viral
suppression

35. Conceptual model
Short-term food support
for substance users
in South India
Temporary food security
Ability to participate in mental health/other programs
Improvement in mental health
Improved health and function:
- Improved family and social interactions
- Decreased HIV risk behaviors
- Decreased alcohol use
- Improved nutritional status
- For HIV+’s: ability to start ART and
improved response to ART
Long-term food security