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

Learning Objectives

Review of scientific evidence:

1. To understand interactions between nutrition

and HIV

2. To understand the nutrition implications of ART

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)

HIV Infection

Insufficient dietary intake

Malabsorption and diarrhea

Impaired storage and altered metabolism

Malnutrition:

Protein-energy malnutrition

Micronutrient deficiencies

HIV – Nutrition Spiral

Nutritionally acquired immunodeficiency

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

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

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

Post-ART rollout:

How does Nutritional Status affect

ART outcomes?

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.

Baseline nutritional status predicts

ART survival

Author, Year Country N Mortality Predictors of Mortality

Severe, 2005 Haiti 1004 10% (6M)13% (12M)

AIDS-defining illness, CD4≤50 cells/µl, low weight (lowest quartile for sex)

Ferradini, 2006 Chiradzuludistrict, Malawi

1266 19% (8M) BMI<18.5, WHO stage IV, male sex, and baseline CD4<50

Paton, 2006 Singapore 394 20% (29M) BMI<17, WHO Stage, non-HAART

Zachariah, 2006 Thyolo district, Malawi

1507 8% (3M)13% (24M)

WHO stage IV, CD4≤50 cells/µl, and BMI<16 kg/m2

Stringer, 2006 Lusaka, Zambia 16,198 5% (3M) CD4 count, WHO stage, BMI<16 kg/m2, severeanemia, and poor adherence to ART.

Calmy, 2006 11 countries (Africa, Asia, Central America)

6861 7% (6M)10% (12M)

Male gender, WHO stages III & IV, BMI<18 kg/m2, CD4<15 cells/µl, Hgb<100 g/l.

Erikstrup, 2007 Zimbabwe 196 HIV RNA level, HB, CD4 cell count, and CDC category

Barth, 2008 Elandsdoorn, South Africa

675 19% (12M) Karnofsky score ≤50, CD4<50

Johannessen, 2008 Tanzania 320 18% (3M)30% (11M)

Moderate/severe anemia, thrombocytopenia, and BMI<16 kg/m2

Marazzi, 2008 Mozambique, Tanzania, Malawi

3456 53% (6M) BMI <18.0 kg/m2, Hgb, clinical staging, viral load, and CD4 cell counts

Toure, 2008 Cote d’Ivoire, West Africa

10 211 15% (18M) Male gender, Age, CD4<150, WHO stages 3 and 4, Hgb, BMI<18.5, type of care center

Srasuebkul, 2009 17 clinics in Asia-Pacific region

1663 29% (20M) BMI≤18, mild to severe anemia, CD4≤200, age≤29

Koethe et al. JAIDS 2010

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]

Madec et al, AIDS 2009

BMI<=17

BMI: >17 to <=18.5

BMI: >18.5 to <=20BMI: >20

ART initiation is associated

with weight gain

Madec et al, AIDS 2009

BMI<=17

BMI: >17 to <=18.5

BMI: >18.5 to <=20

BMI: >20

ART initiation is associated

with weight gain

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.

What we know…

BMI<16.0 BMI 16.00-16.99

BMI 17.00-18.49BMI>18.5

Koethe et al. JAIDS 2010

Baseline BMI and 6 month weight gain as a predictor of mortality

BMI and weight gain at M3* increases

mortality during 3-6 month period

Madec et al, AIDS 2009* M3 = 3 months on ART

Madec et al, AIDS 2009

BMI and weight gain at M6* increases

mortality during 6-12 month period

*M6 = 6 months on ART

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.

BMI and CD4 response

Author, Year Country N BMI predicts CD4 response?

Paton, 2006 Singapore 394 No

Barth, 2008 Elandsdoorn, South Africa

675 Yes (BMI<17.1)

Toure, 2008 Cote d’Ivoire, West Africa

10 211 No

Koethe, AIDS, 2010

Lusaka, Zambia

56,612 Yes, but not clinically significant

Kiefer, 2011 Rwanda 537 F No

Tang (Unpublished)

Vietnam 100 M No

Koethe et al, AIDS 2010

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.

Adjusted hazard ratios of death, by

baseline BMI and CD4 change

Koethe et al, AIDS 20106 months on ART

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

How does Food Insecurity affect

ART outcomes?

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]

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.

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].

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.‟

Barriers to free ART for injecting

drug users (IDU) in India

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.

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.

Barriers to free ART for injecting

drug users (IDU) in India

Chakrapani, 2008

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

Food Insecurity

HIV

• Loss of income

• Loss of labor (farming)

• Cost of ART ($ and time)

Physical:

Under- (or over) nutrition

Psychosocial: Depression, Worry,

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;

• Stigma

• Isolation

• Depression

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.

Low BMI

Food

Insecurity

Early mortality

on ART

Poor CD4 response,

incomplete viral

suppression

HIV and nutrition nexus – which

approach should NACS programs take?

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

Short-term food support

Temporary food security

Ability to participate in mental health/other programs

Improvement in mental health

Long-term food security

Figure 2. Conceptual Model

Conceptual model

for substance users

in South India