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The evolution of HIV complications and the emergence of Non-Communicable Diseases in PLWH

This presentation discusses the evolution of HIV complications and the emergence of non-communicable diseases in people living with HIV. It covers various complications such as osteoporosis, chronic skin conditions, renal insufficiency, and more. The role of antiretroviral therapy and its impact on complications is also discussed.

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The evolution of HIV complications and the emergence of Non-Communicable Diseases in PLWH

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  1. The evolution of HIV complications and the emergence of Non-Communicable Diseases in PLWH Judith S. Currier, MD University of California, Los Angeles

  2. HIV Related Complications

  3. 1000 800 600 400 200 0 Early Complications CD4Cells Late Complications 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Infection Time in Years Course of HIV Infection Ongoing morbidity

  4. HIV Related Complications

  5. Osteopenia/porosis Osteonecrosis Chronic skin conditions Renal insufficiency Hypogonadism Sarcopenia Myopathy Rheumatologic Pulmonary Fibrosis Pulmonary HTN HIV Vitamin D Def Thyroid Diabetes GH Def Visceral Fat Cognitive impairment Neuropathy Chronic diarrhea Atherosclerosis Vascular disease/pulmhtn

  6. Prevalence of Traditional Cardiac Risk Factors in the D:A:D Study • Large cohort of HIV-infected patients on HAART followed longitudinally (N = 23,468) • 18,962 (80.8%) with previous ART exposure; 4506 (19.2%) antiretroviral naive 100 80 60 51.5 Percentage of Cohort With Risk Factor at Baseline 40 33.8 22.2 20 11.4 8.5 3.5 2.5 1.4 0 Family Historyof CHD PreviousHistory of CHD CurrentSmoking BMI> 30 HTN Diabetes ↑ TotalCholesterol ↑ TG Friis-Møller N, et al. AIDS. 2003;17:1179-1193.

  7. Multivariate analysis of percentage change in lipids from baseline to week 48 TDF/FTC ABC/3TC or d4T/3TC 60 60 60 60 DRV/r, 50 50 50 50 SQV/r % change % change 40 40 40 40 ATV/r 30 30 30 30 20 20 20 20 10 10 10 10 0 0 0 0 LPV/r % change % change FPV/r Total cholesterol HDL LDL Triglycerides Meta-analysis of impact of NRTI backbone +PI/r on Lipids Hill A et al. World AIS Conference 2008 Abs THPE0167

  8. MI Rates in HIV compared to Age Matched Controls • Administrative Hospital Database : Acute MI rates in 3851 HIV-infected and 1,044,589 HIV-uninfected patients from 1996-2004 • MI rate per 1000 person-years higher in HIV-infected vs HIV-uninfected patients: 11.13 vs 6.98 120 HIV infected 90 77.68 HIV uninfected 60 Rates per 1000 Person-Yrs 43.63 36.47 33.39 24.47 30 18.74 14.78 10.13 7.56 4.65 3.34 0.88 0 18-34 35-44 45-54 55-64 65-74 75-84 Age Group (Yrs) Triant VA, et al. J Clin Endocrin Metab. 2007;92:2506-2512.( Slide adapted from Tebas- Clinical Care Options)

  9. 10 Protease inhibitors Nonnucleoside reverse-transcriptase inhibitors 9 8 7 6 Incidence per 1000 Person-Yr 5 4 3 2 1 0 0 0 <1 1-2 2-3 3-4 4-5 5-6 >6 Exposure (yr) Use of Protease Inhibitors Increased MI Risk in the D:A:D Study PIs: adjusted RR = 1.16 (1.10-1.23, p<0.001) NNRTIs: adjusted RR = 1.05 (0.98-1.13, p=0.17) DAD Study Group. N Engl J Med 2007; 356:1723

  10. The D:A:D Study PIs/NNRTIs and Risk of MI: Cumulative Exposure to Each Drug PI NNRTI 1.2 1.13 RR/year 95% CI 1 0.9 IDV NFV LPV/r SAQ NVP EFV #PYFU: 68,469 56,529 37,136 44,657 61,855 58,946 #MI: 298 197 150 221 228 221 * Approximate test for heterogeneity: P=0.02 J Infect Dis. 2010 Feb 1;201(3):318-30

  11. Role of ART in Complications • Long term tenofovir exposure and subclinical renal disease, bone loss • Ritonavir and triglyceride increases • Thymidine analogues and subcutaneous fat loss • ART and visceral fat? • ART and vitamin D deficiency?

  12. Role of HIV in CVD: SMART Study • Primary endpoints • OD or death from any cause • CVD/Renal of Liver Disease DC Arm Intermittent ART (n = 2720) HIV-infected patients with CD4+ cell count > 350 cells/mm3 (N = 5472) Study halted prematurely; mean follow-up: 18 mos VS Arm Continuous ART (n = 2752) El-Sadr WM, Lundgren JD et al NEJM 2006; 355:2283–2296

  13. SMART: Non-AIDS Event Rates with Continuous vs Intermittent Therapy • Significantly more individuals in Drug Conservation (DC) arm developed major CV, renal, or hepatic disease than those in viral suppression (VS) arm • Significantly more individuals in DC arm experienced grade 4 event or death from any cause than individuals in VS arm El-Sadr WM, et al. N Engl J Med. 2006;355:2283-2296.

  14. SMART: Non-AIDS Event Rates with Continuous vs Intermittent Therapy • Significantly more individuals in Drug Conservation (DC) arm developed major CV, renal, or hepatic disease than those in viral suppression (VS) arm • Significantly more individuals in DC arm experienced grade 4 event or death from any cause than individuals in VS arm El-Sadr WM, et al. N Engl J Med. 2006;355:2283-2296.

  15. Causes of Death in HIV • Causes of death among 68,669 HIV-infected in New York City • Non-HIV–related deaths increased from 19.8% to 26.3% between 1999 and 2006 • Due to CVD, substance abuse and non-AIDS–defining cancers • Among individuals ≥ 55 years, CVD leading cause of death Sackoff JE, et al. Ann Intern Med. 2006;145:397-406.

  16. Deaths due to Non-AIDS Exceed AIDS Causes in Patients with higher CD4+ Counts 0.8 AIDS Non-AIDS 0.4 Cumulative mortality Non-AIDS Non-AIDS Non-AIDS AIDS AIDS AIDS 0 CD4<200 CD4+ 201-350 CD4+ 351-500 CD4+>500 Adapted, Lau et al, JAIDS 2007

  17. Mortality in HIV has declined but not completely Bhaskaran K, et al. JAMA 2008;300:51-59

  18. Risk of Death in Untreated HIV Infection and CD4+ Cell Counts > 350 cells/mm3 • Analysis of data from 24 cohorts in developed countries • Mortality in treatment-naive patients with CD4+ cell counts > 350 cells/mm3 higher than in matched general population controls • 487 deaths recorded; 4.9/1000 patient-years • HIV-related deaths: 79 (16.2%) • Non-HIV–related deaths: 235 (48.3%) • Unknown cause of death: 173 (35.5%) • Even in patients with high pre-treatment CD4+ cell counts, ↑ CD4 still associated with ↓ risk of death • Rate ratio: 0.95 per 100 cells/mm3 higher (95% CI: 0.90-0.99; P = .0185) Lodwick R, et al. CROI 2008. Abstract 141.

  19. Incidence of Clinical Events after cARTAPROCO/COPILOTE (ANRS CO8) Cohort Study Ferry T et al. JAIDS 2009;51(4): 407-15.

  20. Incidence of Clinical Events after cARTAPROCO/COPILOTE (ANRS CO8) Cohort Study Ferry T et al. JAIDS 2009;51(4): 407-15.

  21. Cancer Incidence in AIDS Patients • Study of cancer risk in AIDS patients from 1980-2006 (N=372,364) • Predominantly male (79%), non-hispanic black (42%), MSM (42%) • Median age of 36 years at the onset of AIDS • Cancer risk in years 3 - 5 after AIDS onset increased for AIDS but also Non-AIDS defining cancers SIR=Standardized Incidence Ratios Simard E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 27.

  22. NADEs in ART treated patients: Botswana compared to US Rate of Non-AIDS events per 1000 person years Wester, CW AIDS 2011 May 12 Epub

  23. HIV Related Complications

  24. Factors Associated with NCD in HIV HOST/ LIFESTYLE VIRUS/IMMUNE SYSTEM ART Understanding the relative contributions of each of these factors to the pathogenesis of complications in HIV will help to inform the development of strategies for prevention and treatment

  25. Estimated Aging Population with HIV in South Africa

  26. Risk Factors for Non-AIDS Events • Immunodeficiency (AIDS 2008;22:841-8) • HIV RNA (JAIDS 2009;51:407-15, CID 2009 49:1109-16) • Markers of inflammation (hsCRP) • Immune activation • Other biomarkers under evaluation for specific events • IL-6 • D-dimer , tissue factor on monocytes (Blood 2010 115;161-7) • Markers of endothelial activation

  27. Summary Our understanding of spectrum of HIV related illness has evolved over the past 30 years. NCD have emerged as an important cause of morbidity in both untreated and treated HIV infection. HIV disease, ART and host factors all contribute to NCD in PLWH The impact of earlier ART on reducing rates of NCD remains under evaluation Many opportunities exist for developing interventions for optimal screening, treatment and prevention of NCDs in settings with high prevalence of HIV

  28. “The secret is to gang up on the problem, rather than each other." - Thomas Stallkamp

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