365   The Effect of Treatment Interruption in Patients with Virologic Failure: Results from a Multi-Cohort Collaborative Study.

Sabin¹, A. Phillips¹, J. Fusco², M. Youle¹, J. Gill³, J. Barbour⁴, A. D'Arminio Monforte⁵, B. Dauer⁶, S. Staszewski⁶, J. Braun⁷, S. Deeks⁴, and V. Miller*⁶.
¹Royal Free Univ., London, UK;²Glaxo Wellcome, Res. Triangle Park, NC;³Calgary, Alberta;⁴Univ. of California, San Francisco;⁵Milan, Italy;⁶Goethe Univ., Germany; and⁷PRN, New York, NY.

Background:Treatment interruptions (TI) occur frequently in patients with virologic failure. The benefits and safety remain unclear. To address these issues, we pooled data from 6 clinical HIV cohorts.

Methods:All ARV-experienced patients interrupting treatment for at least two months with a virus load >5000 copies while taking a minimum of three drugs were included in this retrospective analysis. Factors associated with response to subsequent therapy were assessed using Cox regression models. Participating cohorts were CHORUS, Frankfurt, Royal Free, Alberta, San Francisco, and ICONA.

Results:The preliminary analysis was based on 252 patients. TIs were started between June 1996 and June 2000 with a median length of 4.3 months (60 days to 29.5 months). Patients had been exposed to 6 (3—14) drugs. Nadir CD4 cell counts and peak pVL prior to ARV treatment were 70 cells/mm³and 5.9 log₁₀copies/ml. Median CD4 counts at the start and end of the TI were 207 and 93 cells/mm³

a median drop of 180 cells/mm³(p = 0.0001). pVL at the start and end of TI were 4.84 and 5.53 log₁₀copies/ml, an increase of 0.45 log (p = 0.0001). CD4 changes over TIs were greatest in those with higher pre-TI CD4 counts and in those with lower nadir CD4 counts. Thus CD4 loss was predicted by the formula 12.35 + (0.57 × nadir CD4 count) - (0.72 × pre-TI CD4 count), validated with an independent sample. Following re-initiation of therapy (n = 182), 98 patients experienced at least one pVL <50 copies/ml. Multivariate analysis identified the CD4 cell count (RH per 50 cells: 1.11, p = 0.0001) and pVL at the start of TI (RH 0.72, p = 0.02) and the number of drugs started (RH 1.32, p = 0.0002) as independent predictors of treatment response.

Conclusions:In these heavily ARV-experienced patients, TIs may offer the opportunity to reduce toxicity and allow the emergence of a drug-susceptible virus. However, the long-term clinical impact of the TIs should consider not only the subsequent response to therapy but also the drop in CD4 cell count and rise in viral load during the interruption phase.