400   Effects of Therapy Delay on Virologic Failure in Early HIV.

R. Geise¹, J. Maenza¹, A. Collier¹, S. Holte², C. Stevens¹, D. Hughes¹, and L. Corey.
¹Univ. of Washington and²Fred Hutchinson Cancer Res. Ctr., Seattle.

Background:A patient's initial drug therapy is generally considered the best opportunity to achieve sustained viral suppression. Theoretically, prolonged uncontrolled viral replication during untreated primary HIV infection may lead to de novo mutations and clones that are resistant to antiretroviral medications. The objective of this study was to determine if timing of initiation of HAART affects the likelihood of virologic failure (VF).

Methods:All patients in our cohort (patients diagnosed with HIV within 120 days of infection) started on HAART (defined as at least 3 drugs from two different classes of antiretrovirals) were categorized as having virologically failed HAART based on the following criteria: (1) viral loads greater than the lowest level of detection on two consecutive visits after maximal suppression on HAART or (2) discontinuation of medications for the stated reason of virologic failure. A Cox hazard analysis was performed looking at the effects of delaying HAART on VF.

Results:Seventy-nine patients in our cohort received HAART, of which 11 had VF. Thirty-seven began HAART within 120 days (0 failures), 50 within 1 year (1 failure) and 57 within 2 years (4 failures) of seroconversion. Eighteen patients received therapy prior to HAART, of which 8 had VF. Age, viral load and CD4 count at HAART initiation as well as compliance had no impact on VF. When compared with patients who started therapy within 1 year of seroconversion, patients who delayed therapy greater than 1 year had an odds ratio of 19.34 (p = 0.005) of subsequent VF. Controlling for previous anti-retroviral therapy, the odds ratio for VF due to delay in therapy of greater than 1 year was 9.73 (p = 0.063), and due to previous ART it was 2.90 (p = 0.179).

Conclusion:Therapy delay impacts on the likelihood of virologic failure. Whether the development of de novo mutations during uncontrolled viral replication, therapy delay itself or other unmeasured characteristics affects failure needs to be determined from larger studies.