292   Response to Salvage Therapy in Patients Undergoing a Structured Treatment Interruption.

S. Deeks*, T. Wrin, R. Hoh, T. Liegler, N. Hellmann, J. Barbour, R. Grant, and C. Petropoulos.
Univ. of San Francisco; ViroLogic, Inc, South San Francisco; and Gladstone Inst. of Virology and Immunology, San Francisco, CA.

Background:Among patients experiencing virologic failure, a structured treatment interruption (STI) may result in the emergence of wild-type virus. This may allow a more durable response to subsequent antiretroviral therapy.

Methods:Nineteen patients with a plasma HIV RNA >2500 copies/ml while receiving a protease inhibitor-based regimen underwent an STI. Plasma HIV RNA levels, CD4 cell counts and resistance testing (phenotype/ genotype) were measured weekly during the STI and every 4 weeks after therapy was restarted. Response to salvage therapy was analyzed in those patients followed for at least 24 weeks after reinitiating therapy (ITT).

Results:During a median treatment interruption period of 18 weeks, the median decrease in CD4 cell counts was 95 cells/mm and the median increase in plasma HIV RNA levels was 0.74 log copies/mL. Most subjects received a salvage regimen that included 2 nucleoside analogues, one non-nucleoside reverse transcriptase inhibitor (NNRTI) and two protease inhibitors. Virus from 18 subjects became fully susceptible to protease inhibitors prior to the initiation of salvage therapy. Relative to the date salvage therapy was restarted, 24 weeks of salvage therapy resulted in a median decrease in HIV RNA levels of 1.87 log copies/mL and a median increase in CD4 cell counts of 77 cells/mm. At week 24, 9/19 (47%) of subjects had an HIV RNA <50 copies RNA/mL. Subjects who were NNRTI naïve at study entry were more likely to have a successful response to salvage therapy (7 of 8 NNRTI-naïve and 2 of 11 NNRTI-experienced subjects had an HIV RNA <50 at week 24) (p = 0.006). Failure of salvage therapy was associated with the emergence of virus exhibiting phenotypic and genotypic characteristics identical to or similar to virus present prior to treatment interruption.

Conclusions:These data suggest that highly resistant virus may persist at low levels after drug-susceptible virus emerged in plasma and that such virus may re-emerge under selective pressure. The virologic response to salvage therapy for this experienced patient population was higher than expected. Most patients were able to regain CD4 cells lost during an STI.