Nutrition in HIV-infected patients in Africa

Nutrition in HIV-infected patients in Africa Dave Spencer Kimera Consultants 2007 Diets and HIV Infection „Mrs Tina van der Maas, was a nurse for nine months….15 years ago. Her diet consists of a whole lemon blended or grated, mixed with extra virgin olive oil and water; crushed garlic; ginger cut in small pieces; spinach, beetroot, several vitamin supplements and a solution containing extracts from the African potato.‟ Reported by Jo-Anne Smetherham. The Cape Times. 27 February 2004 Diets and HIV Infection Dr Tshabalala-Msimang confirmed her support of the (dietary) programme saying that “ no one said these diets cure HIV. However they boost the immune system.” The minister went on to say that she had met over 100 patients who had “ got up and walked” after following the dietary advice of Mrs van der Maas…. Reported by Jo-Anne Smetherham. The Cape Times. 27 February 2004 Beetroot, garlic and nutrition in HIV The German physician Matthias Rath admits that his views are “complimentary to what South Africa has been doing”, and describes himself as “the founder of the scientific concept of „Cellular Medicine‟. The systematic introduction into clinical medicine of the biochemical knowledge of the role of micronutrients as biocatalysts in a multitude of metabolic reactions at the “The Rath Foundation is preying on cellular level” vulnerable people with life-threatening Kapp C. World Report. Lancet 2005 (June 4th);365:1916-17 illnesses with two aims: to sell their products and to support the HIV denialists who have caused enormous damage to our country”, TAC said in court papers. Beetroot, garlic and nutrition in HIV „Outside the courtroom there were scuffles between hundreds of TAC supporters and the Traditional Healers‟ Organisation, which has 25 000 members in southern Africa and has allied itself to Rath.‟ „Flanked by David Rasnick, a prominent AIDS dissident and member of President Thabo Mbeki‟s AIDS advisory panel, Rath presented findings of a study in the impoverished township of Khayelitsha which he said was “so encouraging” that it was not sent for peer review. Instead he took out a full-page advertisement in the New York Times and the International Herald Tribune detailing the experiments under the title “Stop AIDS Genocide by the Drugs Cartel”. „ Kapp C. World Report. Lancet 2005 (June 4th);365:1916-17 Diets and HIV Infection Author: Neil M Orr MA Research Psychology UCT David Patient Endorsements: Dr Ashraf Grimwood Peter Doyle Positive Health has borrowed extensively from the ancient art of healing called Ayurveda – the “art of life” – and has shown that even today with this modern epidemic we can rely on old and often forgotten wisdom to meet the challenges of our times. Foreword. A Grimwood Diets and HIV Infection GARLIC: „Garlic is one of the most remarkable plants in the world. Not only does it reduce high blood pressure, increase low blood pressure and reduce cholesterol, it is also the most powerful plant-based antibiotic known, one tenth the strength of penicillin. Unlike the other antibiotics, garlic does not destroy the good bacteria in your stomach, and it is therefore safe to use in large amounts.’ Positive Health 1999, pg 28 Diets and HIV Infection GARLIC: Garlic is best chopped into pieces and eaten raw. Two to three cloves per day prevent many infections, not only worms and parasites. For example, garlic juice can treat ear infections, yeast infections and inhalation of the fumes of chopped garlic in a bowl of hot water – with a towel over your head – helps for chest infections. Garlic will clean out most –it not all- worms and stomach parasites, if eaten regularly and in sufficient quantity. Positive Health 1999, pg 28 Diets and HIV Infection CARROTS (RAW) „Raw carrots contain high levels of a powerful substance called beta carotene – vitamin A -which is very important in dealing with HIV. However, another use for raw carrots is for dealing with worms and other stomach parasites. Eat at least four medium-sized raw carrots once a week for cleaning the stomach. We suggest you eat raw carrots every day – up to four a day.‟ Positive Health 1999, pg 27 Diets and HIV Infection Vitamin C „Vitamin C is a substance that is powerful in fighting viruses including HIV. However this benefit is only found in high doses, 500 to 1000 mg, each dose given three times a day for adults. Positive Health 1999, pg 46 Nutritional Risk How do we assess risk? Cochrane review of micronutrients and HIV Nigel Rollins UKZN/Dept Child Health 2006 • • 38 trials included 1/7 studies reporting on all-cause mortality found a reduction due to vitamin A supplements of 63% in HIV-infected children (RR=0.37 [0.14, 0.95]) Multivitamin supplementation (B,C,E) of BF mothers reduced child mortality among immunologically and nutritionally compromised women in one trial One of four studies reporting on morbidity (including diarrhoea, RTIs and HIV-related symptoms), found a 49% reduction of all diarrhoea in HIVinfected children due to vitamin A Changes in HIV-1 viral load or CD4 counts and other lymphocyte subsets were reported in 8 and 10 studies respectively. No change in VL reported and variable responses in T-cell subsets  • • • The effect of micronutrients on all-cause mortality and on morbidity in HIV-infected adults and children appears to be independent of their effect on HIV viral load or immune markers HIV-associated wasting Total energy expenditure Activity-related Energy Expenditure – (AEE) TEE AEE Resting Energy Expenditure (αBMR) Appetite and ILLNESS … Food intake REE Body fat is spared in HIV-infected children with growth failure 30 P=NS 25 20 HIV+/ G F + HIV+/ G F 10 He a lt h y 15 5 0 Bo d y f a t % Arpadi 1998 Lean tissue (fat-free mass) is reduced in HIV infection even in absence of growth failure 200 150 100 50 0 FFM/ht (gm/cm) Arpadi 1998 P<0.01 HIV+/GF+ HIV+/GFHealthy Growth velocity is inversely related to viral load 12-month growth velocity(cm/yr) vs HIV viral load (HIV RNA copies/ml) performed in HIV-infected children (n=42) • Growth velocity and FFM are inversely related to level of viral replication • Viral replication remains a negative determinant of growth rate even after adjusting for food intake. Nigel Rollins UKZN, 2006 Arpadi 2000 Why wasting? Possible reasons? • Increased energy expenditure – HIV infection itself – Opportunistic infections e.g. TB, fever • Increased losses – Malabsorption – Diarrhoea Nigel Rollins UKZN 2006 Why wasting? Possible reasons? • Increased energy expenditure – HIV infection itself – Opportunistic infections e.g. TB, fever Increased losses – Malabsorption – Diarrhoea • • Decreased intake – Poor appetite – Lack of food – Stress / Depression / Care practices Nigel Rollins 2006 How do we assess risk? HISTORY EXAMINATION “ All that is really needed is a competent examiner, a good scale and a tape measure” LABORATORY Shevitz AH, Knox TA. Nutrition in the Era of HAART. CID 2001;32:1769-75 History: the nutritional “checklist” Adults: What do you eat each day: describe a typical day, yesterday/ today..? When last did you have a meal? How often do you miss meals in a week? What‟s your appetite like? Are you losing or gaining weight? Have you noticed any change in body shape since starting the ARVs? History: the nutritional “checklist” infants and children: Breastfeeding or formula feeds? Exclusive breastfeeding? Formula feeds: AFASS criteria How much milk is the child given/takes? Formula preparation: water supply? heating? cleaning the bottle? Identify the at-risk child AFASS criteria: acceptable, feasible, affordable, safe, sustainable Trends in Maternal Antiretroviral Therapy and Perinatal HIV Transmission, Women and Infants Transmission Study: 1990-2004 60 100 90 50 80 Transmission Rate per 100 70 40 HAART 60 50 40 30 30 Monotherapy 19.4% 17.7% 17.5% 9.0% 6.6% 3.6% 1995 22.3% 20 10 MultiART 3.2% 3.0% 2.1% 1997 1998 20 10 0.9% 1.4% 1.6% 2000 2001 1.2% 0 2003+ 0 1990 1991 1992 1993 1994 1996 1999 2002 Year of Enrollment % Receiving Therapy No ART Reality Check • Even with complete coverage of an effective peripartum ART intervention, an estimated 300,000 children globally will acquire infection through breastfeeding Illif PJ, Piowoz EG, Tavengwa NV et al. (Zimbabwe) Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005;19:699-708 N = 4495 HIV-infected mothers N = 2060 babies HIV-1 PCR –ve and alive at 6 weeks Overall postnatal transmission (+ve HIV test after the initial negative test at 6 weeks) was 12.1% 68% of these transmissions occurred after 6 months ie related to breastfeeding Illif PJ, Piowoz EG, Tavengwa NV et al. (Zimbabwe) Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005;19:699-708 Exclusive breastfeeding (EBF): The infant consumed only breast milk and no other liquids, milks or solids except vitamins or prescribed medication. Predominant breastfeeding (PBF): The infant‟s major source of nourishment is breast milk, but non-milk liquids – water, tea, juice, cooking oil, are also consumed Mixed breastfeeding (MBF): The infant consumed breast and other milks – formula, cow‟s milk, and also solids or semisolids as tolerated. Illif PJ, Piowoz EG, Tavengwa NV et al. (Zimbabwe) Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005;19:699-708 Breastfeeding duration: 99%, 94% and 59.1% of mothers were still breastfeeding at 6, 12 and 18 months respectively EBF: only 156 (7.6%) of infants were exclusively breastfed for at least 3 months. PBF = 490 (23.8%) and MBF = 1414 (68.6%) of infants EBF mothers were slightly older and more likely to be unemployed. The single strongest factor promoting enrollment into the exclusive breastfeeding arm of the study was exposure of the mother to a full course of education and counselling. MBF: a total of 93.2% of all the infants were on mixed feeds by 6 months. Illif PJ, Piowoz EG, Tavengwa NV et al. (Zimbabwe) Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005;19:699-708 Postnatal transmission: E (exclusive) BF: P (predominant) BF: M (mixed) BF: 5.1 per 100 child years of breastfeeding 6.7 per 100 years of breastfeeding 10.5 per 100 years of breastfeeding Severe baseline maternal anaemia (Hb < 7G%) was a significant predictor of PNT Exclusive breastfeeding for the first 6 months carries a risk of 1-2 % Illif PJ, Piowoz EG, Tavengwa NV et al. (Zimbabwe) Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005;19:699-708 Study findings: The introduction before the age of three months of solid food or animal milks to breastfeeding infants is associated with a 4-fold increased risk of PNT at 6 months when compared with EBF The protective effect of EBF is still significant despite a change in the infants diet, when assessed at 18 months post-delivery with a 61% reduction in the incidence of PNT as compared with MBF Illif PJ, Piowoz EG, Tavengwa NV et al. (Zimbabwe) Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005;19:699-708 Study findings: More than two-thirds of PNT occurred after 6 months. This has been verified in studies in West Africa, Tanzania and South Africa and justifies the stopping of breastfeeding EARLY in HIV-positive women Women with CD4 levels < 200 c/cu mm were 5 xs more likely to transmit virus during breastfeeding compared with CD4 counts> 500 c/cu mm. (This study did not check maternal VL levels) Anna Coutsoudis. Strategies to Reduce Breast-feeding transmission and Improve Childhood Mortality. IAPAC Conference, Johannesburg. November 2005 REDUCING RISK: • Promoting exclusive breastfeeding during the first 6 months of life with earlier than usual cessation of breastfeeding. Usual = 6 months • Good lactation management to prevent breast pathology • Good nutrition and prompt treatment of opportunistic infections Anna Coutsoudis. Strategies to Reduce Breast-feeding transmission and Improve Childhood Mortality. IAPAC Conference, Johannesburg. November 2005 REDUCING RISK: • ARV prophylaxis of mother and/or the infant into the breastfeeding period. Several trials currently underway. • Heat treated expressed breast-milk. Particularly from 6 months onwards when women are considering stopping Heat up to 60 C for 30 minutes Diarrhea in children: an interface between developing and developed countries. Thapar N, Sanderson. Lancet 2004;363:641-53 Breastfeeding and Diarrhoea: • Non-breastfed infants are 14-25 times more likely to die from diarrhoea than infants who are exclusively breastfed. • Evidence strongly supports the promotion of breastfeeding for the first 4-6 months of life and its continuation during episodes of diarrhoeal illness. Anna Coutsoudis. Strategies to Reduce Breast-feeding transmission and Improve Childhood Mortality. IAPAC Conference, Johannesburg. November 2005 “when replacement feeding is acceptable feasible affordable sustainable safe avoidance of all breastfeeding by HIV-infected mothers is recommended.” UNAIDS/WHO/UNICEF guidelines: the AFASS criteria Phillipa Musoke Use of Antiretroviral Drugs to provide Infant protection during Breastfeeding. IAPAC Conference, Johannesburg, November 2005 PETRA STUDY Breastfeeding population in Uganda, Tanzania and SA ZDV + 3TC given AP, IP, PP (PP = I week of ZDV + 3TC) By 18 months the benefit of ARVs had been lost Nutrition in the HIV-infected in Africa: Examination Vital messages in HIV nutrition Weight loss is a predictor of death Wheeler DA, Gilbert CL et al. Weight loss as a predictor of survival and disease progression in HIV infection. JAIDS 1998;18:80-85 EXAMINATION • Wasting occurs in more than 20% of patients with AIDS • 5% of men and 20% of women with HIV+ve are obese Shevitz AH, Knox TA Nutrition in the Era of HAART Clinical Infectious Diseases 2001; 32: 1769-75 HIV and weight loss: examination 18% of pt on HAART > 10% BW lost 21% of pt on HAART > 5% BW lost Followed longitudinally over > 1 yr * • Wanke C, Silva M et al CID 2000;31:803-5 HIV and Weight loss: examination Wasting is associated with – – – – Increased mortality Accelerated disease progression Loss of muscle protein mass Decrease in functional capacity Grinspoon S, Mulligan K et al CID 2003; 36 (Suppl 2): S 69-78 Wasting in HIV: examination the repair of chronic wasting will require an increased energy intake • underlying infection? Tuberculosis? Enteric infection? • poverty, access to food Rollins N et al. Executive Summary of a Scientific Review. WHO. Consultation on Nutrition and HIV/AIDS, Durban April 2005 Food and not just supplements and “immune-boosters” is what is needed Hsu JW, Pencharz PB et al Macronutrients and HIV/AIDS: a review of current evidence. WHO Consultation, Durban 10-13 April, 2005 Patient Adults and adolescents Adults and adolescents Children Children Children HIV Stage Asymptomatic WHO Stage 1 Symptomatic WHO Stage 2 Asymptomatic WHO Stage 1 Symptomatic WHO Stage 2 Symptomatic WHO Stage 3 and 4 Total Energy requirements 10% increase 10-30% increase 10% increase 20-30% increase 50-100% increase body mass index = BMI BMI (kg/m²) = weight (kg)/ (height (m))² Shevitz AH, Knox TA Nutrition in the Era of HAART Clinical Infectious Diseases 2001; 32: 1769-75 Willett WC, Dietz WH, Colditz GA. Guidelines for Healthy Weight NEJM 1999;341:427-434 The normal body mass index for males is 20-25 and for females 1924. Overweight is between the upper limits of normal and 30. Obesity is a body mass index greater than 30 Willett WC, Dietz WH, Colditz GA. Guidelines for Healthy Weight NEJM 1999;341:427-434 BMI (Kg/m2) < 18.5 GRADE Under weight 18.5-24.9 25-29 30-40 40+ normal Grade 1 overweight Grade 2 overweight Grade 3 overweight obesity = BMI > 30 kg/m² Classification of BMI (kg/m²) Underweight Normal Range Overweight Pre-Obese Obese Class I Obese Class II Obese Class III <18.5 Risk of Associated Illness Low (but greater risk of other clinical problems) Average Increased Moderate Severe Very severe 18.5 -24.9 ≥25.0 25.0 -29.9 30.0-34.9 35.0-39.9≥40.0 Body Mass Index at time of HIV Diagnosis BMI Median Survival time 0.8 yrs 8.9 yrs <16 ≥ 22 BMI <18 is a significant independent predictor of mortality and is comparable to CD4 count. In adults a loss in cell mass predicts death J Acquir Immune Defic Syndr, 37(2) 2004 Nutrition and HIV in Africa. Dave Spencer 2007 Measurement of Nutritional Status Weight Body Mass Index (BMI) Mid-upper arm circumference (MUAC) Waist circumference (waist:hip ratio) Waist circumference Women: 88 or > cm Men: 102 or > cm Increased risk of ischaemic heart disease Message 1. Loss of weight occurs because: • Some increased energy requirements • An adequate intake of energy during, and after periods of anorexia and opportunistic infections is not maintained – Opportunistic infections especially diarrhoeal illnesses – Mouth sores, change of taste, oesophageal candidiasis – Advancing HIV disease +/- OIs resulting in release of cytokines (inflammatory proteins) that even by themselves can cause loss of appetite Weight loss (especially muscle mass) predicts death Nigel Rollins UKZN 2006 WHO Technical Review Energy and protein needs • Energy needs increase by about 10% in adults and children from the time of infection • During and after severe illnesses, these needs might increase by a further 20-30%. In severely malnourished children this may increase by up to 50100%. • No evidence for increased protein requirements other than in a balanced diet i.e. 12-15% of the total energy intake • Anorexia and poor dietary intake are important causes of weight loss • Improving the diet alone, though, may not result in weight recovery and improvement in clinical status Nigel Rollins 2006 Message 2 • Energy needs increase by – 10% even when asymptomatic – 25-30% with TB, chronic lung disease and persistent diarrhoea – 50-100% when severely malnourished • BUT • …. – This should be in addition to a normal adequate and appropriate intake Nigel Rollins UKZN 2006 Translating energy needs into intake / nutrition support • Set targets – How do you currently decide if and what to give an adult or child with HIV? • Counsel on how to achieve the target – What are the current eating patterns? – What food is available? – Who looks after the child? • Decide if some form of nutrition support is necessary • Use the available systems to help – – – – – – Nutritional supplements Therapeutic feeding Family Food Support School feeding programmes Welfare support – grants Community and other resources Message 3 • Food based approaches are appropriate to increase energy intake by 10%. Know the correct exchanges to guide adults and caregivers of children • Food-based or nutritional supplements can be used to increase intake by 25-30% when patients have conditions with increased nutritional needs. Essential to assess whether normal basic needs are being met • Therapeutic feeding must be given when adults or children are severely malnourished • The family’s access to food must be assessed to ensure a baseline adequate and appropriate nutritional intake Treating Weight Loss in HIV Nutritional Supplementation: “Although some studies have suggested that there is increased benefit from supplements specifically designed for people with HIV infection, such benefits have not been confirmed, and the primary criteria for selection of a specific supplement should be tolerability and cost.” Grinspoon S, Mulligan K et al CID 2003; 36 (Suppl 2): S 69-78 Micronutrients and HIV infection  viral load Oxidative stress Micronutrient deficiencies HIV+ Infections HIV+++ NAIDS  CD4 Henrik Friis Does micronutrient status or intake affect HIV? Increased micronutrient status / intake may affect Transmission of HIV infection •mother-to-child transmissions •sexual transmission •Infectiousness and susceptibility Progression of HIV infection •HIV load, CD4 counts, AIDS, death •Morbidity from other infections •Drug acceptability, efficiency, safety Micronutrient status in HIV Evidence currently reported in literature • Low levels of – vitamins A, C, D, E, B – Zinc, Selenium • ? True deficiency or reflection of disease stage • Will supplements restore body status and improve immune function? Vitamin A • Regular vitamin A supplementation (consistent with current IMCI protocol) reduces diarrhoeal and other morbidity and protects against growth failure – 63% reduction in all-cause mortality in HIV-infected children (RR=0.37 [0.14, 0.95]) Zinc • Appears to be safe in HIV-infected children and does not increase viral load • Appears to confer same benefit as with HIV uninfected children i.e. decreases prevalence of watery diarrhoea • More research required to confirm these findings • No reason to withold zinc supplements from HIVinfected children presenting with diarrhoea Iron and HIV infection Observational studies In vitro studies  Iron supplementation increase viral replication (Boelaert, 1996) ✚  Iron chelation reduces viral replication (Sappey, 1995) ✚ Cross-sectional studies  Storage iron and Hp 2-2 are predictors of viral load (Friis, 2003) ✚  No relationship between iron status and viral load (Semba, 2001) – Cohort studies  Iron intake predictor of survival (Abrams B, 1993) –  Iron chelation prolong survival in Thalassaemia major (Costagliola, 1994) ✚  Excess mortality in HIV+ given Dapsone with iron (Salmon-Ceron D, 1995) ✚  Iron stores in bone marrow associated with mortality (de Monyé C, 1999) ✚  Hp 2-2 associated with higher viral load and shorter survival (Delanghe, 1998)✚ Has iron adverse effects in HIV infection? ✚ Yes – No Iron and HIV infection Intervention trial  Randomised trial in Kenya, re-analysis  Low dose iron supplementation (60 mg twice weekly) Placebo (n=23) Age (y) Male sex Serum ferritin Haemoglobin Iron (n=22) 27.7 5 8.1 113 26.9 7 10.4 115 HIV load baseline 4.93 5.57 4 month Δ 4.21 -0.59 (-0.95, -0.24) 4.71 -0.83 (-1.20, -0.47) Low dose iron supplementation did not increase HIV load Olsen A, JAIDS, 2003 Note • HIV-infected adults and children frequently have anaemia • Not all anaemia is iron deficient • Iron status should be checked before giving supplements • Iron supplements can be given if iron deficiency is present • Iron recommendations for pregnancy still apply Multiple micronutrients and HIV infection Intervention trial  Randomised trial in Thailand (Jiamton S, 2003) 481 HIV+ adults Multimicronutrient or placebo for 48 wks minerals: zinc 30 mg, iron 10 mg, selenium 0.4 mg, copper 3 mg, iodine 0.3 mg, chromium 0.15 mg, manganese 8 mg, magnesium 80 mg vitamins A, B-complex, C, D, E, K Mortality reduced RR 0.53 (95% CI: 0.22, 1.25) RR 0.26 (95% CI: 0.07, 0.97) among those with CD4<100 No effects on HIV load and CD4 counts Jiamton S, Pepin J, Suttent R et al A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-1 infected individuals AIDS 2003;17:2461-69 Thai study. N = 481. CD4 50-550 c/cu mm. Off ARVS/ micronutrients in the preceding 30 days before start of the trial. Urban community living in Bangkok. Randomized to micronutrients vs placebo x 48 weeks Outcome: the death rate in the micronutrient arm was lower than the placebo arm. No difference in CD4 level or plasma viral load Jiamton S, Pepin J, Suttent R et al A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-1 infected individuals AIDS 2003;17:2461-69 Vitamin A 3000 g vitamin B 12 15 mg Betacarotene 6 mg folic acid 100 g Vitamin D3 20 g pantothenic acid 40 mg Vitamin E 80 mg iron 10 mg Vitamin K 180 g magnesium 200 mg Vitamin C 400 mg manganese 8 mg Vitamin B1 24 mg zinc 30 mg Vitamin B2 15 mg iodine 300 g Vitamin B6 40 mg copper 3 mg Selenium 400 g chromium 150 g Cystine 66 mg Subjects took one tablet twice a day po. allowance (RDA) for healthy adults. Daily doses were above recommended daily Jiamton S, Pepin J, Suttent R et al A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-1 infected individuals AIDS 2003;17:2461-69 CD 4 count cells/ cu mm overall < 200 c/cu mm Micro-nutrient Placebo group gp.Mortality rate/ mortality rate/ 100 person years 100 person years Mortality hazard ratio (95% CI) 0.53 (0.22-1.25) P = 0.1 0.37 (0.13-1.06) P = 0.052 4.0 (2.0-8.0) 6.5 (2.7-15.5) 7.7 (4.6-12.7) 16.9 (9.6-29.8) < 100 c/ cumm 9.3 (3.0-28.8) 32.6 (17.5-60.6) 0.26 (0.07, 0.97) P = 0.03 The impact of multiple supplementation on mortality according to CD4 cell count categories. NEJM 2004;351:23-32 A Randomized Trial of Multivitamin Supplementation and HIV Disease Progression and Mortality. Fawzi W W et al N Engl J Med 2004 (July 1st);351:23-32 Tanzanian Vitamin Trial outcome • • • • • Delayed progression to WHO Stage 4 disease Reduced relative risk of death related to AIDS Significantly higher CD4+ and CD8+ Cell Counts Significantly lower viral loads Vitamin A use alone was no better than placebo A Randomized Trial of Multivitamin Supplementation and HIV Disease Progression and Mortality. Multivitamins: Vitamin B1 20 mg Vitamin B2 20 mg Vitamin B6 25 mg Niacin 30 mg Vitamin B12 50 g Vitamin C 500 mg Vitamin E 30 mg Folic acid 0.8 mg Vitamin A: 30 mg betaCarotene + 5000 IU of Preformed Vit A Fawzi W W et al N Engl J Med 2004 (July 1st);351:23-32 vs. RNI (daily intake which meets nutrient requirement for 97.5% apparently healthy individuals in an age and sex-specific population) Vitamin A B1 (thiamine) B2 (ribofl) B6 Niacin B12 Vit C Vit E Folic acid Iron Tz supplement 10,000 RE 20mg 20mg x12-15 25mg 100mg x20 50ug 500mg 30mg 0.8mg 120mg RNI 800RE 1.4mg 1.4mg 1.9mg 18mg 2.6ug 55mg 7.5mg 0.6mg 100mg* • 299 progressed to WHO stage 4 or died of ‘AIDS-related causes’ – – – – 67 of 271 (24.7%) MVS 70 of 268 (26.1%) MVS + Vit A 79 of 272 (29.0%) Vit A only 83 of 267 (31.1%) placebo • MVS vs. placebo – RR 0.71 [95%CI 0.51-0.98; P=0.04] – + reduced progression to stages 3 or 4 • MVS group cf. placebo - higher CD4 and CD8 counts and reduced VL • Adding Vit A reduced the benefit Nutrition and HIV HIGH RISK GROUP unintentional weight loss of > 5-10% body weight chronic oral thrush dysphagia chronic nausea and vomiting chronic diarrhea 2 or more medical co-morbidities failure to thrive in children etc Nerad J, Romeyn M et al CID 2003;36 (Suppl 2): S52-62