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  • I would like to thank the organizers for inviting me to speak at this meeting. As an academic researcher I am really looking forward to these next couple of days hearing about different nutrition programs in the field and to discuss what has and hasn’t worked and next steps.
  • People are starting ART too late – late diagnosis or other issues (stigma, depression, denial)? What are the barriers to starting ART?When to start nutritional support? Prior to ART eligibility? How soon prior and how would these programs work? What factors play a role in poor CD4 response? Nutrition related or not? What role does adherence play? If so, what are the barriers to adherence? It turns out that poor nutritional status not only has a direct biological role in immune response, but also may play a role through ART adherence.
  • HIV puts people/households at risk of food insecurityCost of ART leads to reallocation of funds away from foodDrugs increase appetite – necessary fuel for immune function and body to recuperate from infectionsI put FI in the middle, A mental health person might put mental health in the middle, a nutrition person might put malnutrition in the middle, an ID person might put HIV in the middle. The point is that this diagram should look like a tightly knotted ball of string – most of these arrows can go in both directions, most of the boxes are related to all the other boxes. Pick one link and you will find a multitude of studies that show evidence of an association. But there is no evidence that one of these links is stronger than the other links. Interventions are like pulling at one piece of string to try to unravel the knot. Pull at one string to see what happens, where it leads.
  • Interestingly, the link between BMI and Food Insecurity is not strongly established in the literature. This could depend on how food insecurity is defined. FI incorporates several domains including worry/anxiety about getting enough food, lack of dietary diversity, and insufficient intake. It’s possible that some domains are stronger drivers of food insecurity and therefore FI is not associated with low BMI in certain populations who are food insecure and spend their time finding food but are always anxious about where their next meal is coming from. Important to address physical security and food insecurity first. Otherwise they won’t be good participants in any HIV/ART program or any other prevention program.
  • We hypothesize that for many people in resource-limited and other stressful environments, these syndromes do not represent true mental disorder but rather a normal stress response to an abnormal and stressful environment, partially or largely caused by food insecurity. Similarly, in such environments many substance users may not be physically addicted to alcohol or drugs, but may be self-medicating. Our conceptual model hypothesizes that providing temporary food security will afford individuals a window of opportunity that will enable actions resulting in longer term improvements in mental, physical, and social health. These actions include seeking and responding to mental health counseling, resulting in temporary improvements in many components of health and function (examples listed in box in Figure 2). Improved health and function, in turn, results in longer term enhancement of food security. The effect of a short-term food support intervention would therefore be maintained after the intervention ceases because resulting long-term improvements in mental health and food security feeds back to continued improvements in health and function (both mental and physical) which continue to enhance food security.
  • Transcript

    • 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 ObjectivesReview of scientific evidence:1. To understand interactions between nutrition and HIV2. 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 OrganizationDietary 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 survivalAuthor, Year Country N Mortality Predictors of MortalitySevere, 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<50Paton, 2006 Singapore 394 20% (29M) BMI<17, WHO Stage, non-HAARTZachariah, 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 categoryBarth, 2008 Elandsdoorn, 675 19% (12M) Karnofsky score ≤50, CD4<50 South AfricaJohannessen, 2008 Tanzania 320 18% (3M) Moderate/severe anemia, thrombocytopenia, and 30% (11M) BMI<16 kg/m2Marazzi, 2008 Mozambique, 3456 53% (6M) BMI <18.0 kg/m2, Hgb, clinical staging, viral load, Tanzania, Malawi and CD4 cell countsToure, 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 centerSrasuebkul, 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 responseAuthor, Year Country N BMI predicts CD4 response?Paton, 2006 Singapore 394 NoBarth, 2008 Elandsdoorn, 675 Yes (BMI<17.1) South AfricaToure, 2008 Cote d’Ivoire, 10 211 No West AfricaKoethe, AIDS, Lusaka, 56,612 Yes, but not clinically2010 Zambia significantKiefer, 2011 Rwanda 537 F NoTang 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 change6 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 InsecurityPhysical: 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 – whichapproach 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 – whichapproach should NACS programs take? Low BMI Early mortality on ART FoodInsecurity Poor CD4 response, incomplete viral suppression
    • 35. Conceptual model Short-term food supportfor substance usersin 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