1. Mary Lawrence Hicks, FNP Positive Health Program October 21, 2010

2. What is your field? 1. Family Medicine 2. General Medicine 3. HIV/AIDS 4. Midwifery/gynecology

3. I see HIV+ patients in my practice? 1. Yes 2. No

4. Historical Perspectives: the 80’s  Average lifespan from time of diagnosis: 18 months  AZT licensed March 1987 as monotherapeutic agent  Goals of therapy: prevent opportunistic infections; improve quality of life with decreased symptomatology

5. Course of HIV Infection

6. Historical Perspectives: the 00’s  Delay ARV start until CD4 350 or below  Resistance: save ARVs ‘til you really need them (resistance assays available)  Restoration of immune function demonstrated  Why subject healthy person to SEs?

7. Historical Perspectives: the 90’s  Early 90’s: serial monotherapy  Mid 90’s: Protease Inhibitors usher in the HAART (Highly Active Antiretroviral Therapy) Era  Hit Early Hit Hard: begin ARVs when CD4 count drops below 500  Lost immune function can’t be recovered  Viral load testing becomes available

8. 2010  December 1, 2009 new DHHS Guidelines recommend ARV start with CD4 of 500*  Rationale: Inflammation caused by unsuppressed virus damaging to cardiac, brain, liver and renal tissue  Other considerations: new classes and new agents give more options if resistance develops *SFDPH recommends ARVs @ any CD4 count

9. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents December 1, 2009 Developed by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC)

10. Initiation of Antiretroviral Therapy ART should be initiated: history of an AIDS-defining illness or with CD4 count < 350 cells. Initiate ART, any CD4 count: pregnancy, HIV-associated nephropathy, and HBV co-infection when treatment of HBV is indicated. ART recommended CD4 counts 350 - 500 cells. The panel was divided: 55% of panel members for strong recommendation (A) and 45% for moderate recommendation For patients with >500 CD4 cells, 50% of panel members favor starting antiretroviral therapy ; the other 50% of members view treatment as optional in this setting

11. 500 350

12. Case Study  35 yo male diagnosed 1 year ago  CD4 498; VL 78,000  Pt ambivalent re ARV start

13. What would you recommend? 1. Experts must know what they’re talking about; start ARVs 2. CD4 is high; pt is ambivalent; slow down and assess pt readiness. 3. Why use ARVs; HIV doesn’t cause AIDS

14. Panel members favoring earlier initiation of therapy base their recommendation on several recent developments (1) a recent cohort study demonstrating survival benefit with initiation of antiretroviral therapy at CD4 count >500 (2) untreated HIV infection associated with development of non-AIDS-defining diseases: cardiovascular disease, kidney disease, liver disease, and malignancy (3) availability of more effective, more convenient, and better tolerated ARVs (4) increasing evidence that effective ARV therapy reduces HIV transmission

15. NA-ACCORD Study  Two analyses: 17,517 asx ARV naïve HIV+ pts receiving care 1996-2005 in US & Canada 1 st analysis: 8362 pts. 2084 (25%) started ART @ CD4 351-500; 6278 (75%) deferred ART. After adjusting for multiple variables, deferring group found to have 69% higher risk of death. 2 nd analysis: 9155 pts. 2220 (24%) started ART @ CD4 > 500; 6935 (76%) deferred ART. Among deferred-therapy group, increased risk of death was 94% Kitahata et al. Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival. N Eng J Med 2009; 360: 1815-1826

16. The SMART Study  Multinational trial: 5472 pts with CD4 >350  Pts randomized into continuous ART vs. episodic TX interruption guided by CD4 count.  Study enrollment halted 2o TX interruption group had incr risk AIDS and non-AIDS related events (CV, liver and kidney diseases). The New England Journal of Medicine; November 30, 2006. Vol. 355 No. 22

17. City Endorses New Policy for Treatment of H.I.V. By SABIN RUSSELL, NY Times Published: April 3, 2010  San Francisco public health doctors have begun to advise patients to start taking antiviral medicines as soon as they are found to be infected, rather than waiting ……..  “It’s just too risky,” said Dr. Jay Levy, the U.C.S.F. virologist ……  Dr. Capaldini recognizes that today’s drugs are a vast improvement..“is not ready for prime time.”  ‘ living in happy symbiosis with this virus is delusional,” Dr. Follansbee