1. NUTRITION IN HIV AND AIDS Noel W. Solomons MD CeSSIAM, Guatemala City, Guatemala

2. THE BASICS

3. FIFTY YEARS OF THE INTERACTION OF NUTRITION AND INFECTION Scrimshaw NS, Taylor CE, Gordon JE: THE INTERACTION OF NUTRITION AND INFECTION. Am J Med Sci 1959:237:367-403 Synergistic relationships: – Poor nutrition impairs infection outcomes – Infection impairs nutritional status Antagonistic relationships: – Poor nutritional status improves infection outcomes – Infection improves nutritional status

4. ORIGINS OF CONTEMPORARY INTEREST - The history of the HIV epidemic The first cases of Acquired Immunodeficiency Syndrome (AIDS) were reported in homosexual men in California (1981). In Africa, AIDS was originally termed: slim disease. Wasting (imbalance) and cachexia (consumption) are features of AIDS.

5. GEOGRAPHIC EXTENSION/HOT SPOTS - The epidemiology and geography of the HIV pandemic

6. PREVALENCE/RELEVANCE In 2007, there were 33.2 million people living with HIV. – 32% of all new cases occurred in Sub-Saharan Africa – HIV prevalence is >15% in 8 countries: (Botswana, Lesotho, Mozambique, Namibia, South Africa, Swaziland, Zambia, Zimbabwe) – In 2007, there were 2.1 million children living with HIV and 290,000 AIDS-related deaths worldwide.

7. THE RETROVIRUSES

8. The Pathophysiology of HIV Infection and AIDS The HIV proliferates in CD4 T lymphocytes. The virus can spread cell to cell. Major effects are a debilitation of the immune system. The energetics of weight loss include endocrine abnormalities and primary decreases in intake. HIV/AIDS produces a mucosal enteropathy that impedes nutrient absorption. HIV produces neuronal cell death associated with cognitive dysfunction and dementia.

9. Stigma and the Social Pathology of HIV Any contagious disease carries a certain stigma, and avoidance by others aware of the infection. HIV has a series of additional features that increase the level of stigma. These include the facts that AIDS is a fatal disease, it is contracted by sexual contact, and its optimistic infections, e.g. tuberculosis, are themselves contagious. The AIDS patient is the contemporary equivalent of the Leper. The stigma (if it is fatal, what can I do about it? If I have it, I have been unfaithful or my partner has!) deters individuals from seeking diagnostic testing. The advent of effective antiviral regimens (HAART) prolonging life has changed the equation, but the stigma persist.

10. Family and Community Food Insecurity with HIV/AIDS HIV infection in parents affects caring capacity of the mother and work/earning capacity of infected adults. Household and community food security suffers. Mitigation efforts include: school-feeding for sibs and orphans; direct food assistance; agricultural support with labor-saving interventions.

11. UPDATES THE EMERGING (BIOLOGICAL-EPIDEMIOLOGICAL-CLINICAL) ISSUES

12. HIV TRANSMISSION TO CHILDREN Modes of Transmission Vertical Transmission: common, early infancy: in utero; during parturition; through breast milk (mother- to-child transmission =MTCT) Parenteral Exposure: possible, any age: infected hypodermic needle; transfusions (accident; sickle cell disease, thalassemia) Sexual Contact: rare, late childhood and adolescence: child abuse; promiscuity; arranged marriage

13. HIV TRANSMISSION TO CHILDREN Cumulative risk of MTCT About half of all vertical transmission is via human milk. The estimated cumulative risk of MTCT is 9 transmissions per 100 child-years of breast- feeding. The rate is constant per month (0.74% per month of BF).

14. HIV TRANSMISSION TO CHILDREN Risk Factors from Feeding Practices Replacement feeding conveys a virtually zero risk of HIV transmission. Its risk is that of morbidity and mortality from food-borne infection (contamination) or nutritional deficiency (improper formulation) Exclusive breastfeeding produces a lower MTCT than mixed (breast – complementary feeding), with estimates varying widely from 10 to 400% lower transmission risks, depending upon study and setting.

15. PREVENTION OF HIV TRANSMISSION TO CHILDREN First Option: Replacement Feeding: The WHO (2001) recommended: When replacement feeding is acceptable, feasible, affordable, sustainable and safe (AFASS), avoidance of all breastfeedging by HIV-infected mothers is recommended. Problem: If safety criterion is not met, the risk of early death from food-borne illness outstrips the long-term risk for transmission and AIDS mortality

16. PREVENTION OF HIV TRANSMISSION TO CHILDREN Second Option: Exclusive Breast Feeding: When the conditions for replacement feeding are not met, exclusive breastfeeding should be adopted by the HIV+ mother. Quandary: Once begun, the full cessation of breastfeeding should be as abrupt as possible to minimize the mixed-feeding interval. The original specification was at 6 months. This was moved back to 4 months. Recent studies provide no evidence to prefer either weaning interval (Kuhn et al, 2008).

17. PREVENTION OF HIV TRANSMISSION TO CHILDREN WHO/UNAIDS/UNICEF. Feeding Options

18. PREVENTION OF HIV TRANSMISSION TO CHILDREN WHO/UNAIDS/UNICEF. Feeding Options

19. MANAGEMENT OF FEEDING IN HIV INFECTED INFANTS FIRST RULE OF INFANT FEEDING: Once an infant is confirmed to be HIV positive, transmission is no longer an issue -- Breastfeeding (preferably, exclusive) is the indisputably preferred mode of feeding. Problem: Sero-diagnosis requires 6 months for the maternal antibodies to clear from the infant, to provide an infant-specific diagnosis. Only, more expensive virus-specific methods can provide HIV diagnosis at birth.

20. MANAGEMENT OF FEEDING IN HIV INFECTED INFANTS Seeds of a dilemma: According to Saloojee and Copper: Children with HIV and AIDS require high- energy, nutrient-dense diets and may require up to 200% of the recommended daily allowance. There are insufficient data to support a routine increase in protein intake. Fat requirements are unchanged.

21. MANAGEMENT OF FEEDING IN HIV INFECTED INFANTS Human milk is neither high-energy nor nutrient dense, and its daily production has an upper limit, especially in a sick mother. Increasing energy implies complementary feeding. Doubling energy intake with constant protein and lipid, would place full dependence for the increase on carbohydrate. Fat is the most efficient energy source. The anorexia and secondary effects of the underlying HIV infection present barriers to the infants taking the age-specific requirements, much less twice the usual intake.

22. MICRONUTRIENTS IN ADULT HIV INFECTION An entire decade of an agenda of looking to single or multiple micronutrient supplements as low-cost, innocuous nutritional anti-retrovirals or nutritional anti-opportunistics for adult women has been reported. [eg Fawzi, Semba] – Vitamin A produces adverse effects – Multiple micronutrients (- vit A, - Fe) mildly supportive – Selenium supplementation improves hemoglobin and health

23. MICRONUTRIENTS IN PEDIATRIC HIV INFECTION All of the mechanisms for nutrient deficiency are operative. In HIV infection, increasing with progression According to Saloojee and Copper: Micronutrient deficiencies (such as vitamin A, selenium and zinc) are common and may accelerate progression of HIV disease, which in turn leads to worsening of nutritional status.

24. MICRONUTRIENTS IN PEDIATRIC HIV INFECTION Zinc supplementation: Suspected to be harmful. Proved to be beneficial to pediatric AIDS patients in South Africa (Bobat et al 2005) Vitamin A supplementation: Harmful in adult women (Fawzi 2006). Early life supplementation of HIV-infected infants enhances growth (Villamor et al 2002) Iron supplementation: suspected to be harmful. In one clinical trial from Western Kenya, no differential risk was observed between iron supplemented and not-supplemented (Olsen et al 2004)

25. LIPODYSTROPHY AND THE CHILD The new anti-retrovirals fall into 3 categories: Protease inhibitors (PIs), Nucleoside reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Adverse metabolic reactions such as lipodystrophy syndrome and mitochondrial toxicity are related to duration of HAART and age of the subject.

26. DRUG – NUTRIENT INTERACTION WITH ANTI-RETROVIRAL MEDICATIONS Foods and nutrients on anti-retroviral drugs: – Various traditional herbs change the intestinal uptake of Nevirapine, enhancing absorption. Anti-retroviral drugs on nutrients: – HIV protease inhibitors block conversion of 25- OH-vitamin D to 1,25-OH-vitamin D.

27. TAKE-HOME MESSAGES: HIV/AIDS HIV/AIDS is a worldwide pandemic, with maximal intensity in sub-Saharan Africa, that has diverse implications for nutrition and food security. Vertical transmission is the most common – but not the only – mode of infection with HIV. The method chosen for the feeding of the infant of an HIV-infected mother will be a major determinant in the both the risk of infant infection and the risk of early mortality.

28. TAKE-HOME MESSAGES: HIV/AIDS The default feeding choice is replacement milks if the situation meets AFASS criteria, with EBF to 6 mo being the option. Mixed feeding is a no no! The use of ART and HAART to avoid MTCT is in its infancy. Interactions and tolerance of anti-retrovirals in children is poorly understood. Not only is the mother-child dyad a focus of nutritional concern, but the entire family unit and the communities at large are at risk of household food insecurity.

29. SUGGESTED READING Gillespie S. AIDS, Poverty and Hunger: Challenges and Responses. Food Policy Statement. Washington, International Food Policy Research Institute, 2006. Saloojee H, Cooper P. HIV and AIDS. In: Koletzko B (ed) Pediatric Nutrition in Practice. Basel, Karger 2008:162-167. Solomons NW, ODonnell GE. HIV and the remifications for food security and child health in affected communities. Annales Nestle 2007;65:9-28. Kuhn L, Aldrovandi GM, Sinkala M, et al. Zambia Exclusive Breastfeeding Study. Effects of early, abrupt weaning on HIV- free survival of children in Zambia. N Engl J Med 2008;359:130- 141.

30. Thank You