A Look Back at the International A Look Back at the International AIDS Conference MeetingAIDS Conference Meeting

Lessons from IAC 2010Lessons from IAC 2010

A Clinical Context ReportA Clinical Context Report

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A Look Back at the International AIDS A Look Back at the International AIDS Conference Meeting—Lessons from IAC 2010Conference Meeting—Lessons from IAC 2010

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A Look Back at the International AIDS A Look Back at the International AIDS Conference Meeting—Lessons from IAC 2010Conference Meeting—Lessons from IAC 2010

Clinical Context SeriesClinical Context SeriesTarget AudienceTarget Audience

The goal of this program is to provide HIV/AIDS The goal of this program is to provide HIV/AIDS specialists, virologists, infectious disease specialists, virologists, infectious disease specialists, experts in the care of patients with specialists, experts in the care of patients with HIV/AIDS, physician assistants and nurse HIV/AIDS, physician assistants and nurse practitioners with up-to-date informationpractitioners with up-to-date informationand multiple perspectives on the pathogenesis, and multiple perspectives on the pathogenesis, symptoms, risk factors, and complications of symptoms, risk factors, and complications of HIV/AIDS as well as current and emerging HIV/AIDS as well as current and emerging treatments and best practices in the management treatments and best practices in the management of HIV/AIDS.of HIV/AIDS.

Activity Activity Learning ObjectivesLearning Objectives

Upon successful completion of this Upon successful completion of this educational program, participants should educational program, participants should be able to:be able to:

Discuss the results of this report from IACDiscuss the results of this report from IAC Review the relevance and significance of the Review the relevance and significance of the

report in the broader context of clinical carereport in the broader context of clinical care

CME Information: PhysiciansCME Information: Physicians

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Albert Einstein College of Medicine Albert Einstein College of Medicine designates this educational activity for a designates this educational activity for a maximum of 0.25 maximum of 0.25 AMA PRA Category 1 AMA PRA Category 1 Credits.™ Credits.™ Physicians should only claim Physicians should only claim credit commensurate with the extent of credit commensurate with the extent of their participation in the activity.their participation in the activity.

CME Information: NursesCME Information: Nurses

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Barry S. Zingman, MD Medical Director

AIDS CenterMontefiore Medical Center

Professor of Clinical Medicine Albert Einstein College of Medicine

Bronx, NY

DiscussantDiscussant

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Barry S. Zingman, MD,has disclosed that he has no relevant financial has disclosed that he has no relevant financial

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activity.activity.

Disclosure InformationDisclosure InformationDori F. Zaleznik, MD, Associate Clinical Professor of Medicine, Harvard Medical School, Boston; Michael Smith and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner, have disclosed that they have no relevant financial have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.related directly or indirectly to this educational activity.

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SummarySummary

The most recent guidelines suggest that HIV The most recent guidelines suggest that HIV therapy should start at a CD4 count of at least 500therapy should start at a CD4 count of at least 500

The treatments of choice to start therapy are now, The treatments of choice to start therapy are now, increasingly, fixed dose combination pillsincreasingly, fixed dose combination pills

A vaginal microbicide that includes an antiretroviral A vaginal microbicide that includes an antiretroviral drug, tenofovir, has shown efficacy in preventing drug, tenofovir, has shown efficacy in preventing HIV acquisition in a randomized controlled trialHIV acquisition in a randomized controlled trial

The product has also appeared to lower the risk of The product has also appeared to lower the risk of acquiring herpes simplex virus 2, a known risk acquiring herpes simplex virus 2, a known risk factor for HIVfactor for HIV

Recommendations for Initiating Antiretroviral Therapy (ART) in Treatment-Naïve Adults with HIV-1 Infection Who Are Ready to Begin Therapy

• ART is recommended regardless of CD4 cell count for persons with symptomatic HIV disease, pregnancy, active HBV or HCV co-infection, or those at high risk for secondary HIV transmission

• ART is recommended for asymptomatic adults with CD4 cell counts 500/μL

• ART should be considered in patients who are asymptomatic with CD4 cell counts > 500/μL, unless the patient is an elite controller (HIV-RNA <50 copies/mL) or has a stable CD4 count and low-level viremia in the absence of ART

Why Start ART Earlier

• NA-ACCORD study demonstrated that there was lower mortality, as well as significantly lower non-age defining events, if people were started on ART before their T-cell count dropped to 500

• If therapy is not started until the patient’s CD4 count is <500, there is a lower chance that CD4 count will become normal on therapy

• Several studies have demonstrated that HIV transmission between serodiscordant couples and in injection drug users is decreased with ART

CASCADE Cohort

• 9,455 HIV recent seroconverters, avg. age 30

• 812 (8.6%) developed AIDS

• 544 (5.8%) died

• Relative effects: AIDS/Death• CD4 count 0-49 – Incidence Rate per 1000 person years 193.3

Defer ART, 55.0 Initiate – adjusted HR 0.32 (95% CI 0.17,0.59)

• CD4 50-199 – IR 56.6 Defer, 22.0 Initiate aHR 0.48 (0.31, 0.74

• CD4 200-349 – IR 29.4 Defer, 18.7 Initiate aHR 0.59 (0.43, 0.81)

• CD4 350-499 – IR 20.8 Defer, 17.2 Initiate aHR 0.75 (0.49,1.14)

• CD4 500-799 – IR 18.5 Defer, 14.9 Initiate aHR 1.10 (0.67, 1.79)

CASCADE Caveats

• Retrospective study of patients who had recently seroconverted

• Significantly smaller than the 20,000 to 50,000 patients followed over years in NA-ACCORD and HIV-CAUSAL

• Looked only at death not• AIDS-related cancers

• Cardiovascular disease

• CD4 counts

• Prevention of kidney disease

New Treatment Recommendations, ISA-USA

• The committee came out in favor of fixed-dose combinations

• Tenofovir/emtricitabine number one recommended NRTI combination

• Abacavir/lamivudine secondary NRTI• Third component should be either

• Efavirenz

• A ritonavir-boosted protease inhibitor such as darunavir/ritonavir or atazanavir/ritonavir

• Integrase inhibitor raltegravir

• Lopinavir/ritonavir moved to 2nd line because of toxicity

  # HIV infections/

women years HIV incidence

Incidence Rate Ratio

P Value

  Tenofovir Placebo

Tenofovir gel

Placebo gel

   

Overall effectiveness of tenofovir gel

HIV endpoints 38 / 680.6 60 / 660.7 5.6 9.1 0.61 0.017

HIV endpoints by levels of adherence

High adherers (>80% gel adherence)

11 / 259.2 25 / 269.4 4.2 9.3 0.46 0.025

Intermediate adherers(50-80% adherence)

10 / 159.8 10 / 99.7 6.3 10 0.62 0.343

Low adherers(<50% gel adherence)

16 / 258.5 25 / 290.6 6.2 8.6 0.72 0.303

Modified from Karim, et al. Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women. Science. Published Online July 19, 2010 at: http://www.sciencemag.org/cgi/rapidpdf/science.1193748.pdf. Reprinted with permission from AAAS.

Impact of Tenofovir Gel on HSV-2 Incidence

 Tenofovir gel

n=202Placebo gel

n=224

# HSV-2 infections 29 58

Women-years (wy) of follow-up 292.3 287.3

HSV-2 incidence per 100wy (95% CI)

9.9(6.6, 14.2)

20.2(15.3, 26.1)

IRR = 0.49 (CI:0.30, 0.78); P = 0.003

51% protection against HSV-2 by tenofovir gel (CI: 22%70%)

Results of the CAPRISA 004 Trial. Presented by Salim Abdool Karim, July 20, at the XVIII International AIDS Conference, Vienna, Austria. Oral Abstract TUSS0504.