Hit Hard, Hit Early: When to Treat and With What?

Brian G. Gazzard, MD, Moderator

Julio Montaner, MD

Calvin J. Cohen, MD, MS

Faculty Disclosure

Brian G. Gazzard, MD

No real or apparent conflicts of interest to report.

Julio Montaner, MD

Research grants, advisory boards, speakers bureaus:

Abbott, Argos Therapeutics, Bioject Inc, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Janssen-Ortho, Merck Frosst, Panacos, Pfizer, Schering Serono Inc. TheraTechnolgies, Tibotec (J&J), Trimeris

Calvin J. Cohen, MD

Consulting fees, fees for non-CME services, contracted research:

Abbott, Bristol-Myers Squibb, Gilead Sciences, Merck, Pfizer, Tibotec

Hit Hard, Hit Early: When to Treat and With What?Brian G. Gazzard, MA, MD, FRCPConsultant Physician and Research Director, HIV/GUMChelsea & Westminster HospitalLondon, UK

Cumulative Mortality Estimates

Calculated Using Extended Kaplan-Meier Survival Estimates

CD4 >500 & defer HAART (n=6539)

CD4 >500 & initiate HAART (n=2616)

Years After 1996

0.00

0.05

0.10

0.15

0.20

0 2 4 6 8 10

Kitahata M et al . 16th CROI; 2009; Montreal. Abstract 71.

CD4 Threshold (cells/mm3)

0.5

1

2

4

H

azar

d R

atio

0 100 200 300 400 500

Note that successive comparisons are not statistically independent

Sterne J et al . 16th CROI; 2009; Montreal. Oral Abstract 72LB.

Hazard Ratios for AIDS or Death, Adjusted for Lead Times and Unseen Events

Assume you are HIV positive and have a CD4 count of 500 cc/mL. You have two options. Which would you choose?

1. $10,000 in the bank annually earning compound interest until your CD4 count is 350 cc/mL

2. Start ART immediately

Hit Early?

At what CD4 cell count would you start for the benefit of the patient?

STARTMRK: Percent of Patients With HIV RNA <50 Copies/mL (95% CI) (Non-Completer = Failure)

281 279 281 279 281 279 278 280 280282 282 282 282 281 282 280 281 281

Raltegravir 400 mg bida

Efavirenz 600 mg qhsa

Number of Contributing Patients Weeks

Per

cen

t o

f P

ati

en

ts

0 2 4 8 12 16 24 32 40 48

0

20

40

60

80

100

82%

NoninferiorityP Value <.001

86%

aIn combination with tenofovir/emtricitabine.Lennox J et al. 48th ICAAC–46th IDSA; 2008; Washington, DC. Abstract H-896a.

MERIT-ES Re-analysis: Kaplan-Meier Plot of Time to Virologic Failure (≥50 Copies/mL)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 100 200 300 400 500 600 700

Only patients with an R5 screening result by enhanced Trofile assay are included.Nonresponders (failure, rebound, discontinuation) were censored.

MVC + ZDV /3TC

EFV + ZDV /3TC

Su

rviv

al E

stim

ate

Days

Heera J et al. 5th IAS; 2009; Capetown. Abstract TUAB 103.

3TC, lamivudine; EFV, efavirenz; MVC, maraviroc; ZDV, zidovudine.

Time to Virologic Failure (Plasma HIV RNA >200 log10 copies/mL)

No shorter time to undetectable viral load, but significantly shorter time to virologic failure. Consistent for other HIV RNA thresholds

0.00

0.25

0.50

0.75

1.00

97 97 97 93 91 89ZDV/ABC + TDF/FTC105 105 105 104 103 102ATV/r + TDF/FTC111 111 111 109 109 108EFV/TDF/FTC

Number at risk

0 4 12 24 36 48

Weeks

EFV/TDF/FTC

ATV/r + TDF/FTC

ZDV/ABC + TDF/FTC

Arm HR P

EFV/TDF/FTC 1

ATV/r + TDF/FTC 0.88 0.840

ZDV + ABC + TDF/FTC 3.30 0.012*

ABC, abacavir; ATV/r, ritonavir-boosted atazanavir; EFV, efavirenz; FTC, emtricitabine; TDF, tenofovir; ZDV, zidovudine.

Cooper D. 5th IAS; 2009; Capetown. Abstract LBPEB09.

Hit hard?

What agent would you start with?

Why would you no longer start with efavirenz?