1. Slide 1 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. IAS–USA David Alain Wohl, MD Associate Professor of Medicine The University of North Carolina at Chapel Hill Aging and HIV From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA.

2. Slide 2 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. A 35 yo man, non-IDU, diagnosed with HIV starting HIV therapy at CD4>200 can expect to live into his 70’s ART-CC, The Lancet, 2008, 372:293-299

3. Slide 3 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA.

4. Slide 4 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA.

5. Slide 5 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. 4% 6% Poly-pathology is more common in HIV+ patients and increases with age Co-morbidities included: hypertension, diabetes mellitus, hypothyroidism, cardiovascular disease, bone fractures. CasesControls 100% 41 to 50 yrs51 to 60 yrs> 60 yrs  40 yrs 41 to 50 yrs51 to 60 yrs> 60 yrs  40 yrs n = 542n = 1,724n = 452n = 136 No age-related diseases2 co-morbidities1 co-morbidity3 co-morbidities4 co-morbidities n = 1,626n = 5,172n= 1,356n= 408 0% 75% 50% 25% 90% 9% 80% 17% 65% 28% 6% 40% 42% 15% 80% 16% 3% 60% 31% 8% 42% 35% 17% 21% 31% 29% 15% 1% 2%1% 2% 0.25% Polypathology (Pp) prevalence among HIV+ cases and HIV-uninfected controls, by age categories. Pp prevalence3.9%9.0%20.0%46.9%0.5%1.9%6.6%18.7% Guaraldi G, et al. CID 2011;53:1102-1126.

6. Slide 6 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. COHERE Study: Baseline Virologic and Immunologic Profile by Age Baseline HIV RNA HIV RNA (log 10 copies/mL) 13-17 4.8 18-2930-39 40-49 50-54 55-59 >60 4.8 5.0 5.1 4.9 COHERE Study Group. AIDS. 2008;22:1463-1113. Age at Baseline (years) CD4 (cells/mm 3 ) 13-17 222 18-2930-39 40-49 50-54 55-59 >60 256 188 178 173 210 Age at Baseline (years) Baseline CD4 Count

7. Slide 7 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. COHERE Study: Response by Baseline Age Achieving CD4 Count >200 Cells/mm 3 at 12 Months Patients (%) 13-17 85.6% 18-2930-39 40-49 50-54 55-59 >60 86.7% 76.3% 75.2% 73.9% 74.7% 80.5% COHERE Study Group. AIDS. 2008;22:1463-1113. Age at Baseline (years) Patients (%) 13-17 18-2930-39 40-49 50-54 55-59 >60 Age at Baseline (years) New AIDS Event At 12 Months P<0.0001 for trend 4.8% 5.2% 8.5% 9.6% 9.3% 7.0% 9.7% P<0.0001 for trend

8. Slide 8 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. COHERE Study: Continuation of HAART by Baseline Age COHERE Study Group. AIDS. 2008;22:1463-1113. Patients (%) 13-17 18-2930-39 40-49 50-54 55-59 >60 Age at Baseline (years) Discontinuation of All ARTs at 12 Months 15.3% 14.8% 9.2% 6.9% 7.9% 11.4% 7.3% P<0.0001 for trend ●Similar rates of discontinuing or switching >1 antiretroviral agent during the first 12 months of HAART ●Complete treatment discontinuation was rare - Lower rates were observed among those >40 years of age

9. Slide 9 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. Kaiser Permanente Northern California: Immunologic Response and Age 0 1 2 3 4 5 6 Time After HAART Initiation (years) CD4 Cell Count CD4 Count (cells/mm 3 ) Years of Age 18 to 39 (n=2259) 40 to 49 (n=1834) >50 (n=997) Silverberg MJ, et al. Arch Intern Med. 2007;167:684-691. P=0.001 P=0.07 P=0.66 ● CD4 gains 1 year after HAART initiation were lower in the older group (P=0.046) - 18-39 years of age +131.8 cells/mm 3 - 40-49 years of age +121.38 cells/mm 3 - >50 years of age +111.8 cells/mm 3 ● Despite blunted initial immunologic responses in the older group, CD4 counts were similar by year 3

10. Slide 10 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. DHHS. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

11. Slide 11 of 11 From DA Wohl, MD, at New York, NY: May 03, 2012, IAS-USA. MACS: Frailty Phenotype in HIV-Positive MSMs 50 to 70 Years of Age Prospective cohort of MSMs (2009-2010) –2850 person-visits –HIV positive on HAART (n=1451) –HIV negative (n=92) Ages 50 to 70 years –Frailty phenotype more common in HIV-positive men versus HIV-negative men May be effect of HIV infection, HAART, or both Further longitudinal studies are needed Age Group (years) Prevalence (%) 5% Prevalence of Frailty Phenotype <4040-4950-5960-69>70 Desquilbet L, et al. 18 th CROI. Boston, 2011. Abstract 794. HIV-positive on HAART HIV-negative 4% 8% 15% 8% 20% 10% 33% 24%