Nutrition, Adherence, Metabolic Side Effects. ALASTAIR DUNCAN HIV Specialist Dietitian, Guy s and St. Thomas Hospital

1. Nutrition, Adherence, Metabolic Side Effects. ALASTAIR DUNCAN HIV Specialist Dietitian, Guy�s and St. Thomas� Hospitals, London.

2. Topics Covered Conference Snippets Nutrition Nutrition and HIV in Developing Countries Developments in HIV Nutrition Adherence to Antiretrovirals Conference snapshots Metabolic Side Effects New Stuff Reinforcement of current knowledge

3. This slide shows estimates of the number of people living with HIV by regions of the world, and includes the numbers of new infections and deaths estimated for the year 2003. Well over 50% of infected individuals live in sub-Saharan Africa, with Asia the next most affected region. An estimated 4.8 million new infections occurred during 2003, and the number of deaths was estimated at 2.9 million globally. For more information, please go online to: http://www.unaids.org/bangkok2004/report.html This slide shows estimates of the number of people living with HIV by regions of the world, and includes the numbers of new infections and deaths estimated for the year 2003. Well over 50% of infected individuals live in sub-Saharan Africa, with Asia the next most affected region. An estimated 4.8 million new infections occurred during 2003, and the number of deaths was estimated at 2.9 million globally. For more information, please go online to: http://www.unaids.org/bangkok2004/report.html

4. Main Drivers of HIV Epidemic, by Region Sub-Saharan Africa: Heterosexual transmission Asia: IDUs, MSM, sex workers, clients, partners China: Urban: IDUs Rural: Results of contaminated plasma selling India: sexually acquired (heterosexual/homosexual, sex workers) Border with Myanmar: IDUs Eastern Europe & Central Asia: IDUs USA, Canada, Western Europe: MSM, IDUs Depending on the region of the world, there are different drivers for the HIV epidemic. This does not mean that these are the only means of transmission in a particular region, but rather that these are the most frequent modes of transmission, or the ones that seem to be pushing the epidemic forward. In sub-Saharan Africa, it is heterosexual transmission. In Asia, there is a larger number of injection-drug users and men who have sex with men, but there is also heterosexual transmission from sex workers to their clients and then from the clients to their partners. In Eastern Europe and in Central Asia, there is a preponderance of injection-drug users, and in the United States, Canada, and Western Europe, men who have sex with men, injection-drug users and, to a lesser extent, heterosexual sexual transmission drive the HIV epidemic, although heterosexual transmission appears to be increasing substantially in some regions of the US in particular. For more information, please go online to: http://www.unaids.org/bangkok2004/report.html Depending on the region of the world, there are different drivers for the HIV epidemic. This does not mean that these are the only means of transmission in a particular region, but rather that these are the most frequent modes of transmission, or the ones that seem to be pushing the epidemic forward. In sub-Saharan Africa, it is heterosexual transmission. In Asia, there is a larger number of injection-drug users and men who have sex with men, but there is also heterosexual transmission from sex workers to their clients and then from the clients to their partners. In Eastern Europe and in Central Asia, there is a preponderance of injection-drug users, and in the United States, Canada, and Western Europe, men who have sex with men, injection-drug users and, to a lesser extent, heterosexual sexual transmission drive the HIV epidemic, although heterosexual transmission appears to be increasing substantially in some regions of the US in particular. For more information, please go online to: http://www.unaids.org/bangkok2004/report.html

5. Four Conference Themes Access to Resources: Commitment and Accountability Scaling up Access to Treatment The Global Fund for AIDS, TB and Malaria WHO 3 by 5 Ensuring Access for Youth and Women Two-thirds of all new HIV diagnoses are now in women Expanding Options and Access for Prevention Access was perhaps the inevitable theme around which the XV International AIDS Conference would be organised. But this was not just about access to treatment. The conference organisers - the International AIDS Society, the Thai Ministry of Health and their community and UN co-organisers - agreed a five track approach (basic science; clinical research, treatment; epidemiology and prevention; social and economic issues; policy and programme implementation) with two additional programmes: leadership and community. Each of the four main conference days was assigned a theme, shown here, around which plenary, oral, poster and skills building sessions were grouped. Following eight days of intensive meetings and conference sessions there was some optimism that Bangkok might prove to be the kind of watershed that the 2000 IAC in Durban certainly was. There, the success was to raise the possibility of expanded access to treatment and demonstrate to the world in vivid language and pictures how sub-Saharan Africa was suffering without it. Four years later there is a maturity to the debate, and some important developments in pricing, funding and political commitment have changed the context for the discussion. Bangkok�s legacy - with luck - could be the introduction of balance and realism to the national and international AIDS programmes of the next five years.Access was perhaps the inevitable theme around which the XV International AIDS Conference would be organised. But this was not just about access to treatment. The conference organisers - the International AIDS Society, the Thai Ministry of Health and their community and UN co-organisers - agreed a five track approach (basic science; clinical research, treatment; epidemiology and prevention; social and economic issues; policy and programme implementation) with two additional programmes: leadership and community. Each of the four main conference days was assigned a theme, shown here, around which plenary, oral, poster and skills building sessions were grouped. Following eight days of intensive meetings and conference sessions there was some optimism that Bangkok might prove to be the kind of watershed that the 2000 IAC in Durban certainly was. There, the success was to raise the possibility of expanded access to treatment and demonstrate to the world in vivid language and pictures how sub-Saharan Africa was suffering without it. Four years later there is a maturity to the debate, and some important developments in pricing, funding and political commitment have changed the context for the discussion. Bangkok�s legacy - with luck - could be the introduction of balance and realism to the national and international AIDS programmes of the next five years.

6. Conference Snippets Big bad old USA

7. Conference Snippets Sex Workers teach safer sex Whor-I-gami: Australian sex worker peer education whilst folding towels

8. Conference Snippets Inspirational individuals Bhutani physician Tanzanian community nurse Fafafine community worker

9. HIV Nutrition in Developing Countries www.aids2004.org (3821) Seeds of survival: AIDS prevention, nutrition and food production training for PLWHA Seven million agricultural workers have died of AIDS since 1985, FAO estimates that another sixteen million may die by 2020 This Partnership Program provides training in nutrition, food production and encourages income generation in Kenya and Tanzania. Cascade training: 244 local staff trained, then providing follow-up training to over 15,000 yearly

10. HIV Nutrition in Developing Countries (1076) Impact on HIV with home nutrition gardens USAID-funded program in Zimbabwe - drip irrigation technology using 50% less water, increases yields, 3 rotations per growing season, reduced manual labour for those ill with HIV. Costs of the kits can be recovered in less than one growing season if used for a cash crop. Gardens supporting at least 75,000 people already established, meeting the complete vegetable needs of each households, plus additional cash income of $20 to $120 per year - improved access to healthcare and education. (7290) Breastfeeding HIV positive mums lose more weight than HIV negative.

12. Developments in HIV Nutrition Health Outcomes and Botanicals (7280) Echinacea and Ginko biloba associated with beneficial outcomes (e.g. physical function, reduced pain) Marijuana and Grape Seed Extract associated with detrimental outcomes (e.g. reduced general health) No product assoc. with improved CD4 or reduced VL. Low serum selenium is associated with low serum albumin and not necessarily poor immune function (3393)

13. Developments in HIV Nutrition Antioxidant function in HIV pts is significantly lower than controls and well below the published ref range (3275) Vitamin D deficiency and insufficiency highly prevalent in children and adolescents with HIV. Poor vitamin D status significant predictor of low BMD in HIV positive children (4467) Multivitamins slow decline of immune system and reduce mortality rates in those not on HAART (3742, 4497)

14. Adherence Drug use and adherence (5765) Marijuana improves adherence in those with nausea No effect on adherence in those without nausea Other illicit drugs associated with non-adherence Home Education and Adherence (5783) Home visits by nurses, carrying out education improves adherence Adherence of >90% associated with VL<50 Sustained Adherence using 4-6 wks DOT (5785) IVDUs � DOT HAART for 4-6 wks in care home Results in improved long-term viral suppression What Factors Affect Adherence? (5815) Side effects most common reason for failure Least tolerable SEs � Diarrhoea, nausea and fatigue � all reported as being worse than body shape changes.

15. Adherence � Slide 2 Doctor Patient Communication (5834) Patient honesty about non-adherence poor despite friendly atmosphere and free-flowing conversation Patients very rarely bring up adherence themselves Best results where permission to admit non-adherence given first, e.g. �many people find it hard to adhere�� What Does �I Forgot� Really Mean? (5817) �I forgot to take my pills� the most common reason for non-adherence But actually only 16% of these actually �forgot� Real reasons � most common first - Didn�t have pills to take, procrastination, in public with family/friends, meal restrictions.

16. Metabolic Side Effects (5852) Omega-3s, fibrates or diet & exercise for HAART-related hypertriglyceridaemia (Italy) 156 patients on 2 nucleosides + 1 PI in 103 or NNRTI in 41 Monitored for 18 months 2 g Omega 3s /day n=54 Bezafibrate, fenofibrate, or gemfibrozil n=53 Diet & exercise programme n=49 Normal trigs achieved in 25 patients in Omega 3 group, 18 in fibrate group, and 4 in diet/exercise group. (5926) Comparative study of 3 fillers, durability at 48 weeks Comparison of polylactic acid (NewFill) (n=30), Polyacrylamide gel (n=90), and autologous fat transfer (n=9) Polyacrylamide gel most durable filler at 48w (resorption rate 3% vs. >85% for fat transfer and polylactic acid).

17. Metabolic Side Effects, Slide 2 Good correlation between anthropometry, US, and CT scans for limb composition (5950) Correlation between Kaletra serum levels and degree of lipodystrophy (5945) D4T in children delays growth (4437) Only 18% of children on HAART have normal lipids (5884) Those with raised triglycerides highly likely to have many other risks for CVD. In this group, smoking cessation reduces CVD risk by 42% (1234) Metabolic Parameters During Supervised Treatment Interruption (5857) Lipids normalise quickly, but slow if any improvement in insulin resistance and body fat.

18. Longer Duration of HAART Associated With Increased Incidence of Osteonecrosis � (1358) This figure illustrates the association between longer duration of HAART and increased risk of osteonecrosis, as described in the previous slide. In this large cohort, other previously reported correlates, such as use of corticosteroids, were not significantly associated with osteonecrosis.This figure illustrates the association between longer duration of HAART and increased risk of osteonecrosis, as described in the previous slide. In this large cohort, other previously reported correlates, such as use of corticosteroids, were not significantly associated with osteonecrosis.

19. Metabolic effects of switching d4T or ddI to tenofovir (4508) N=16F, 38M Age 45.6 yrs (av) HAART regimen included d4T and/or ddI Viral suppression > 6 months secure contraception (women) Control group continued original regimen F/U at 1, 3 and 6 months Exclusion criteria TDF intolerance Cirrhosis/hepatitis Psychiatric illness Creatinine >1.4mg/dl

20. Kaletra vs Atazanavir: Use of Metabolic Therapies (5957)

21. Exercise � Oxandrolone in Patients on HAART (1059) 32 patients completed 12 weeks of follow-up No change in LDL or HDL from exercise alone; worsening with oxandrolone Unfortunately, treatment for lipodystrophy remains disappointing, reinforcing the need to prevent it by using regimens that are less likely to be associated with it. In a study of patients comparing exercise alone vs exercise plus oxandrolone, there was minimal benefit of the additional of oxandrolone. Although total lean mass increased in the patients who received oxandrolone, overall there were no significant changes in fat and, particularly, in subcutaneous fat, suggesting that the addition of oxandrolone to exercise did not greatly benefit the body composition changes that are seen in patients who develop lipodystrophy. Furthermore, the addition of oxandrolone appeared to worsen lipids: LDL cholesterol increased and HDL cholesterol decreased with oxandrolone compared with patients who exercised only. Surprisingly, in this study, exercise alone did not have a beneficial effect on lipids. Whether this relates to the minimal amount of exercise in the study or other complicated factors is unclear, but certainly the worsening lipids and the lack of substantial benefit in body composition seen with oxandrolone suggest that this is not a useful therapy in patients with lipodystrophy. For more information, please go online to: http://clinicaloptions.com/hiv/conf/iac2004/cs/1059.asp Unfortunately, treatment for lipodystrophy remains disappointing, reinforcing the need to prevent it by using regimens that are less likely to be associated with it. In a study of patients comparing exercise alone vs exercise plus oxandrolone, there was minimal benefit of the additional of oxandrolone. Although total lean mass increased in the patients who received oxandrolone, overall there were no significant changes in fat and, particularly, in subcutaneous fat, suggesting that the addition of oxandrolone to exercise did not greatly benefit the body composition changes that are seen in patients who develop lipodystrophy. Furthermore, the addition of oxandrolone appeared to worsen lipids: LDL cholesterol increased and HDL cholesterol decreased with oxandrolone compared with patients who exercised only. Surprisingly, in this study, exercise alone did not have a beneficial effect on lipids. Whether this relates to the minimal amount of exercise in the study or other complicated factors is unclear, but certainly the worsening lipids and the lack of substantial benefit in body composition seen with oxandrolone suggest that this is not a useful therapy in patients with lipodystrophy. For more information, please go online to: http://clinicaloptions.com/hiv/conf/iac2004/cs/1059.asp

22. The Food Chain (London!) Meals and groceries for London�s housebound people with HIV Any health professional can refer 020 7272 7272 www.foodchain.org.uk