Report Back from CROI 2010

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1 Report Back from CROI 2010 Conference on Retroviruses and Opportunistic Infections Edwin Charlebois, MPH PhD Associate Professor of Medicine Department of Medicine University of California, San Francisco Center for AIDS Prevention Studies (CAPS)

2 Highlights from CROI 2010 Accelerated Aging & Badness in HIV HIV Testing & Treatment HIV Transmission

3 CROI 2010 is Wired! (actually it was wireless ) Audio & Video replays of all plenary and most oral abstract sessions Abstract Search of 2010 conference and prior conferences available

4 " data/files/webcast_2010.htm"

5 ctsearch/default.aspx?conf=19

6 Accelerated Aging & Badness in HIV Decreased Life Expectancy Cardiovascular Disease & Smoking Cancers Kidney Disease Neurocognitive Impairment Bone Fractures

7 Life Expectancy and Mortality in HIV-Infected Patients ART-CC: Depending on when ARV therapy is started, life expectancy is yrs less than that in uninfected pts Life expectancy for pts at age 20 was 32 yrs for pts with CD4+ < 100 cells and 50 yrs for pts for CD4+ > 200 cells [1] AQUITAINE cohort: Pts with CD for 6 yrs after combination ARV therapy attained mortality similar to general population [2] COHERE cohort: HIV-infected men, but not women, reached mortality rates similar to uninfected population after 3 yrs of CD cells [3] ATHENA cohort: For asymptomatic HIV-infected pts diagnosed from who remained ARV naive and without AIDS at Wk 24 after diagnosis, modeled life expectancy similar to age- and sex-matched uninfected controls in Netherlands [4] 1. Antiretroviral Cohort Collaboration. Lancet. 2008;372: Lewden C, et al. J Acquir Immune Defic Syndr. 2007;46: Lewden C, et al. CROI Abstract Van Sighem A, et al. CROI Abstract 526.

8 Hsue P, et al. CROI Abstract

9 Hsue P, et al. CROI Abstract

10 HIV is associated with more rapid progression of atherosclerotic progression & related to markers of inflammation (CRP) Hsue P, et al. CROI Abstract 125

11 D:A:D Study: Smoking Cessation Reduces Risk of CVD in HIV-Infected Patients Cessation of tobacco smoking reduced risk of MI, coronary heart disease, and CVD in HIV-infected patients No association of time since smoking cessation and mortality risk IRR of MI* Never Smoked Previous Current Baseline Smoking < 1 yr 1-2 yrs 2-3 yrs 3+ yrs Stopped Smoking During Follow-up Petoumenos K, et al. CROI Abstract 124.

12 Risk of Non-AIDS Defining Cancers in HIV-Infected Patients Retrospective analysis of Kaiser Permanente database, Cancer n Infection related Anal 14 0 HIV Infected (n = 19,280) Rate/100,00 0 py HIV Uninfected n (n = 202,313) Rate/100,00 Adjusted HR* (95% CI) 0 py ( ) Hodgkin s *Adjusted for age, sex, smoking, 44 overweight, 54alcohol/drug 29abuse, viral hepatitis (10.6- lymphoma Incidence of liver, kidney, blood, lung, colorectal, and prostate cancers 29.7) not higher in HIV-infected vs HIV-uninfected patients Oral/pharyngeal ( ) Silverberg M, et al. CROI Abstract Infection

13 Immunodeficiency, HIV-1 RNA, and Risk of Non-AIDS Defining Cancers Recent HIV-1 RNA levels not significantly associated with non-aids defining cancer risk (infection related or non-infection related) Adjusted HR* HIV Infected, CD4+ Cell Count, cells/mm 3 Silverberg M, et al. CROI Abstract 28. < P Value Any infection related <.001 Anal <.001 Hodgkin s lymphoma <.001 Oral/pharyngeal Any infection unrelated Melanoma Lung Colorectal *Adjusted for age, sex, smoking, overweight, alcohol/drug abuse, viral hepatitis; reference = uninfected cohort. P <.001 relative to uninfected. P <.05 relative to uninfected.

14 Cumulative ARV Exposure and Risk of Chronic Kidney Disease in EuroSIDA 6843 HIV-infected patients with 3 serum creatinine measures and corresponding body weight measures from EuroSIDA study 21,482 patient-yrs of follow-up Cumulative exposure to TDF, ATV, LPV/RTV, or IDV each associated with increased risk of chronic kidney disease Risk of chronic kidney disease after stopping TDF remained elevated for 1 yr Within 12 mos, IRR: 4.05 ( ) After 12 mos, IRR: 1.12 ( ) Risk of chronic kidney disease after stopping ATV or LPV/RTV similar to patients never exposed Kirk O, et al. CROI Abstract 107LB.

15 Low CD4+ Count Nadir Associated With HIV-Associated Neurocognitive Disorders CHARTER: prospective observational study (N = 1525) Risk of HIV-associated neurocognitive disorders associated with lower CD4+ nadir, but not current CD4+ cell count Association remained significant after adjusting for other predictors: HIV-1 RNA, age, sex, race, duration of infection Odds Ratio for Cognitive Impairment Ellis R, et al. CROI Abstract 429. < CD4 Nadir

16 Dao C, et al. CROI Abstract 128.

17 Adj. Hazard Ratio=1.6, p<0.05 for Nadir CD4+ cell count < 200 (vs 350) Dao C, et al. CROI Abstract 128.

18 HIV Testing & Treatment SF Community Viral Load & HIV incidence Test & Treat Strategies in SF & Less HIV Expanded HAART coverage & Less HIV Expanded Testing in DC & Earlier CD4 Presentation Treatment in Early HIV infection HIV Testing, Disclosure & HIV Transmission Risk Behavior

19 Das M, et al. CROI Abstract 33.

20 Das M, et al. CROI Abstract 33.

21 Das M, et al. CROI Abstract 33.

22 Das M, et al. CROI Abstract 33.

23 Das M, et al. CROI Abstract 33.

24 Das M, et al. CROI Abstract 33.

25 The Effect of Expanded Antiretroviral Treatment (ART) Strategies on the MSM HIV Epidemic in San Francisco Deterministic modeling of Test & Treat in SF Utilized real-world data from SF surveillance Evaluated 3 expanded ART strategies Expanded ART scenarios versus Standard of care arm: (Treat MSM with CD4<350) 1. Treat all MSM with CD4<500 cells/mm3 2. Treat all MSM who are HIV(+) 3. Treat all + MSM and perform annual HIV testing to detect new infections Charlebois E, et al. CROI Abstract 996.

26 Charlebois E, et al. CROI Abstract 996.

27 HIV Infections Averted Charlebois E, et al. CROI Abstract 996.

28 Jansen I, et al. CROI Abstract 35.

29 Probability of Being Infected by Steady Partner: age patterns Overall Infection Source: Casual Partner 74% Steady Partner 26% Jansen I, et al. CROI Abstract 35.

30 Reduction in New HIV Diagnoses in BC: Testing, HAART, and Community VL Period of declining new HIV diagnoses in BC coincident with increased HIV testing rates, increased uptake of antiretroviral therapy, and decrease in community viral load ( ) Decline in new HIV diagnoses despite increases in syphilis, gonorrhea, chlamydia Patients (n) 12,000 10, New HIV+ diagnoses (all) Censored at the time of death or move New HIV+ Diagnoses (n) HIV-1 RNA, copies/ml < ,000-49,999 50, Montaner J, et al. CROI Abstract 88LB.

31 Castel A, et al. CROI Abstract 34..

32 Impact of Expanded HIV Testing in Washington, DC 3.7-fold increase in number of publicly funded HIV tests performed in Washington, DC, from : 19, : 72,866 17% increase in number of new HIV/AIDS name-based case reports from Significant reduction in time to progression to AIDS following HIV diagnosis from (P <.0001) Time interval between diagnosis to entry into care significantly improved from Castel A, et al. CROI Abstract 34.. Median CD4+ Cell Count (cells/mm 3 ) Median CD4+ cell count at time of HIV diagnosis significantly increased from P <.05 for trend Yr of Diagnosis

33 SETPOINT: ARV Therapy in Early HIV May Delay Time to Meeting Treatment Criteria DSMB stopped trial in June 2009 due to futility of answering primary virologic setpoint question Significantly shorter time to meeting step 2 criteria among patients not receiving early treatment vs those receiving early treatment (P <.001) Possible modest impact of early ARV therapy on subsequent HIV-1 RNA level off treatment Mean HIV-1 RNA for early treatment 3.99 log 10 copies/ml vs 4.15 log 10 copies/ml for no treatment arm at Wk 72 Hogan C, et al. CROI Abstract 134. Pts Meeting Step 2 Eligibility Criteria (%) Early treatment (n = 39) No early treatment (n = 40) Wk 36 Wk 72 in VL at Wk 72 for both arms: P =.005 Difference in VL at Wk 72 for early ART arm (ie, after 36 wks off ART) vs at Wk 36 for no early ART arm: P =.002

34 Mwangi M, et al. CROI Abstract KAIS - Kenya

35 Mwangi M, et al. CROI Abstract 38.

36 HIV Transmission ART Reduces HIV Transmission Risk Factors for Discordance in Couples HIV Transmission During Pregnancy

37 Donnell D, et al. CROI Abstract 136.

38 Donnell D, et al. CROI Abstract 136.

39 349 (10%) initiated ART, No change in sexual act frequency Donnell D, et al. CROI Abstract 136.

40 Donnell D, et al. CROI Abstract 136.

41 Donnell D, et al. CROI Abstract 136.

42 Kaiser R., et al. CROI Abstract 40.

43 Kaiser R., et al. CROI Abstract 40.

44 Kaiser R., et al. CROI Abstract 40.

45 Kaiser R., et al. CROI Abstract 40.

46 2035 HIV(-) at ANC Pregnant Kenyan women retested 6 months post partum 53 (2.6%) now HIV(+) Kinuthia J.., et al. CROI Abstract 155.

47 1398 HIV(-) Women in Swaziland tested at delivery Kieffer M.., et al. CROI Abstract.

48 Thank You!

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