147. Assessment of Time to Loss of Virologic Response (TLOVR) when Comparing Atazanavir/Ritonavir (ATV/r) to Efavirenz (EFV) in AIDS Clinical Trials Group (ACTG) Study A5202: Is TLOVR a Misnomer?
Session: Oral Abstract Session: HIV Primary Care and Antiretroviral Therapy, Epidemiology and Testing
Friday, October 21, 2011: 9:30 AM
Room: 157ABC
Background: TLOVR is a composite endpoint of: i) lack or loss of virologic response, ii) death and iii) premature study drug or follow-up discontinuation that is recommended by the U.S. FDA for drug approvals.  We apply TLOVR to a clinical trial of 4 commonly used antiretroviral regimens for initial treatment of HIV infection.

Methods: In this secondary analysis of A5202, data from 1857 participants were summarized for TLOVR.  Open-label ATV/r was compared with EFV, with change in abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) excluded from the TLOVR algorithm.  Time-to-event distributions and hazard ratios (HR) were estimated by Kaplan-Meier (KM) method and Cox proportional hazards model.

Results: (25th,75th%ile) follow-up was 138 (106, 169) weeks.  Of 688 TLOVR events, 142 were TLOVR-virologic failure (VF) on initial EFV or ATV/r with confirmed viral load above 200 copies/ml and 46 were site declared VF.  The other 500 events were due to modification of EFV or ATV/r (Rx) or premature study discontinuation with 199 (29%) for toxicity, clinical event, HIV progression or death.  Differences in EFV vs. ATV/r with ABC/3TC were driven by modifications that occurred more frequently on EFV+ABC/3TC (Table).

 

 

EFV +

ABC/3TC

(n=465)

ATV/r +

ABC/3TC

(n=463)

EFV +

TDF/FTC

(n=464)

ATV/r +

TDF/FTC

(n=465)

TLOVR

Total number of events

204

180

158

146

96 week: TLOVR-free probability (KM)

63%

70%

72%

76%

96 week: ATV/r – EFV difference (95%CI)

7% (1%, 13%)

4% (-2%, 10%)

Estimated HR (EFV ref.) (95% CI)

0.83 (0.67, 1.02)

0.89 (0.70, 1.12)

Type of event, n (%)

TLOVR-VF on Rx

29 (6%)

45 (10%)

33 (7%)

35 (8%)

Rx modification for site declared VF (non-TLOVR-VF)

22 (5%)

6 (1%)

17 (4%)

1(<1%)

Rx modification or study discontinuation for:

   Toxicity

   Clinical event, progression or death

   Other reasons*

57 (12%)

 12 (3%)

84 (18%)

35 (8%)

15 (3%)

79 (17%)

40 (9%)

4 (1%)

64 (14%)

29 (6%)

7 (2%)

74 (16%)

*non-compliance, participant/clinician request, relocation, incarceration, pregnancy, or never started, ran out of or unable to swallow medications

Conclusion:  In ACTG A5202, only 27% of TLOVR events were due to virologic failure.  With current HIV regimens, the TLOVR endpoint more frequently assesses drug modification and premature study discontinuation than loss of virologic response.


Subject Category: H. HIV/AIDS and other retroviruses

Camlin Tierney, Ph.D.1, Katie Mollan, M.S.1, Eric Daar, MD2, Margaret Fischl3, Ann C. Collier, MD4, David Katzenstein, MD5, Laurie Myers, M.S.6, Daniel Muenz1 and Paul Sax, MD, FIDSA7, (1)Harvard School of Public Health Center for Biostatistics in AIDS Research, Boston, MA, (2)Harbor-UCLA Medical Center, Torrance, CA, (3)University of Miami, Miami, FL, (4)University of Washington, Seattle, WA, (5)Stanford University Medical Center, Stanford, CA, (6)Frontier Science & Technology Research Foundation Inc., Amherst, NY, (7)Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Disclosures:

C. Tierney, None

K. Mollan, None

E. Daar, Abbott: Research Contractor, Research support
Bristol Myers Squibb: Consultant, Consulting fee
GlaxoSmithKline: Consultant and Research Contractor, Consulting fee and Research grant
Gilead: Consultant and Research Contractor, Consulting fee and Grant recipient
Merck: Consultant and Research Contractor, Consulting fee and Research grant
Pfizer: Research Contractor, Research grant

M. Fischl, Abbott Laboratories: Grant Investigator, Research grant

A. C. Collier, Gilead Sciences: Investigator, Research support
Bristol-Myers-Squibb: Shareholder, stocks
Abbott Laboratories: Shareholder, stocks

D. Katzenstein, None

L. Myers, None

D. Muenz, None

P. Sax, Abbott: Consultant, Consulting fee
BMS: Investigator and Scientific Advisor, Consulting fee and Research grant
Gilead: Investigator and Scientific Advisor, Consulting fee and Research grant
Merck: Investigator and Scientific Advisor, Consulting fee and Research grant
GSK: Consultant and Investigator, Consulting fee and Research grant
Tibotec: Investigator and Scientific Advisor, Consulting fee and Grant recipient

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.