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

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

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

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

Course of HIV Infection

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?

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

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 any CD4 count

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)

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 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

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

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

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

NA-ACCORD Study  Two analyses: 17,517 asx ARV naïve HIV+ pts receiving care in US & Canada 1 st analysis: 8362 pts (25%) started CD ; 6278 (75%) deferred ART. After adjusting for multiple variables, deferring group found to have 69% higher risk of death. 2 nd analysis: 9155 pts (24%) started 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:

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, Vol. 355 No. 22

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