526 
Predictors of Clinical Response to Salvage Therapy in a Late Salvage Population with Multidrug-resistant HIV in the OPTIMA Trial
Joel Singer*1, D Ayers1, D Cameron2, M Holodniy3, S Brown4, T Kyriakides5, A Babiker6, A Anis1, M Youle6, and M Schechter1
1Canadian HIV Trials Network, Vancouver, Canada; 2Ottawa Hosp, Canada; 3VA Palo Alto Hlthcare System, CA, US; 4VAMC, Bronx , NY, US; 5VA Cooperative Studies Prgm Coordinating Ctr, West Haven, CT, US; and 6Med Res Council Clin Trials Unit, London, UK
Background: Early virologic and
immunologic response to salvage therapy may be of use in predicting clinical
progression. This analysis examined the prognostic value of baseline CD4, early
(24-week) plasma viral load, and CD4 response to salvage therapy for subsequent
AIDS or death in the context of OPTIMA, an ongoing strategy trial.
Methods: Patients (target N = 504) with plasma viral load ≥2500
copies/mL, a CD4 count ≤300/mm3 on
ART were randomized in a 2 x 2 factorial design to: 3-month ART drug-free period (ARDFP) vs no ARDFP followed by a new standard ART (≤4 ART)
or MegaART (≥5 ART) regimen. A 1-log drop in
viral load at 6 to 24 weeks was considered successful. Clinical events prior to
the 24-week viral load determination were excluded from the analysis. The Cox
proportional hazards model was used to examine the association between
predictors and clinical outcomes.
Results: At onset of salvage
therapy, patients had a mean viral load of 5.0 log and
a CD4 count of 111. Mean follow-up time was 1.8 years. Of 307 evaluable patients, 167 (54.4%) had a successful virologic response at 6 to 24 weeks post onset of treatment,
of whom 13.2% had a primary clinical event (AIDS or death) compared with 37.9%
for failures; the corresponding death figures were 7.2% and 27.1%. Of patients
with CD ≤50 at onset of treatment, 46.1% had a clinical event (AIDS or
death) compared with 14.1% for CD4 51 to 200 and 7.7% for CD4 >200;
corresponding figures for death were 34.8%, 9.0%, and 3.9%. Of patients who had
a CD4 increase ≤90 at 24 weeks, 32.1% progressed to AIDS or death
compared with 6.2% of those with increases ≥90, corresponding figures for
death were 22.1% and 3.1%. In a Cox multivariate regression model, CD4 at onset
of treatment (RH = 0.874 per 10 cell increase, p <0.001), CD4 change (RH = 0.907 per 10-cell increase, p <0.001), and log viral load change
at week 24 (RH = 1.49 per log increase, p
= 0.09), were all important predictors of subsequent AIDS or death. Similar
trends were observed for predictors of death alone: CD4 at onset of treatment (RH = 0.877 per 10-cell
increase, p <0.001), CD4 change
(RH = 0.906 per 10-cell increase, p <
0.002), and log viral load change at week 24 (RH = 1.81 per log increase, p = 0.18).
Conclusions: The
likelihood of progression to AIDS or death, or death alone, in a late salvage
population is predicted independently by CD4 at salvage onset, and CD4 and
viral load change at 24 weeks post-onset.
|
