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Session 100 Poster Abstracts
Strategies of Antiretroviral Therapy
Friday, 1:30 - 3:30 pm
Hall A


582    
Factors Associated with Time to CD4 Count < 350/mm3 after a Treatment Interruption following Effective Antiretroviral Therapy with or without Interleukin-2: Results of a Pilot Prospective Randomized Trial (ACTG A5102)
Keith Henry*1, P Tebas2, D Cherng3, J Schmitz4, D Katzenstein5, H Valdez6, N Jahed7, M Blanchard Vargas7, L Myers8, W Powderly9, and the Adult AIDS Clinical Trials Group
1Univ of Minnesota, Minneapolis, USA; 2Univ of Pennsylvania, Philadelphia, USA; 3Harvard Sch of Publ Hlth, Boston, MA, USA; 4Univ of North Carolina at Chapel Hill, USA; 5Stanford Univ, CA, USA; 6Case Western Reserve Univ, Cleveland, OH, USA; 7ACTG Operations Office, Silver Spring, MD, USA; 8Frontier Sci & Tech Res Fndn, Amherst, NY, USA; and 9Washington Univ, St Louis, MO, USA

Background:  The potential utility of intermittent ARV strategies would be enhanced if clinicians could recognize factors identifying individuals who could be safely maintained off ART for longer periods. ACTG A5102 was designed to evaluate the effect of 3 cycles of interleukin-2 (IL-2), given prior to treatment interruption, on clinical and surrogate marker outcomes in patients who undergo a prolonged treatment interruption using a CD4+ T-cell count of < 350 cells/mm3 as the threshold for restarting potent ART.

Methods:  In this study, we evaluated the associations between time to CD4 < 350 cells/mm3 during treatment interruption and biological markers both at baseline and during treatment interruption using a Cox proportional hazard model with 1 predictive variable at a time. We randomized 47 HIV+ subjects on potent ART with CD4+ T-cell counts > 500 cells/mm3 and HIV-1 RNA levels < 200 copies/mL to arm A (ART + three 5-day cycles of IL-2 at 4.5 million units subcutaneously twice a day every 8 weeks [n = 23]) or arm B (ART only [n = 24]) for 18 weeks (step 1); 21were on a PI-based therapy. At the end of step 1, all study subjects with CD4 count > 500 cells/mm3 underwent a treatment interruption until the CD4 count decreased to < 350 cells/mm3 (step 2). At the time of the analysis, the median follow-up time on treatment interruption was 78 weeks.

Results:  Of the baseline variables analyzed, only a higher nadir CD4 count before the initiation of HAART (unit = 50 cells; HR = 0.49 with 95% CI 0.33 to 0.73; p = 0.0003) and a higher naïve CD4 count at entry (unit = 50 cells, HR= 0.77 with 95% CI = 0.62 to 0.96; p = 0.02) were associated with a longer treatment interruption. Among variables during the treatment interruption, only the log viral set point (unit=1 log10 copy, HR= 3.88; 95% CI = 1.05 tot 14.26; p = 0.042) was significant. The positive effect of IL-2 on maintaining a higher CD4 count during treatment interruption was transient (Kaplan-Meier plots overlap by week 72). Age, changes in CD4+ cell count from nadir to both study entry and the beginning of treatment interruption, type of ART, and T-cell activation markers did not predict the duration of treatment interruption.

Conclusions:  This study represents a unique cohort of HIV+ subjects with a history of effective ART followed long-term after a treatment interruption. The positive effect of IL-2 given while on ART on preserving the CD4 count during treatment interruption was lost by 72 weeks. Our results suggest that in the setting of intermittent ART strategies, starting ART earlier (when the CD4 count is higher) and interventions aimed at decreasing the HIV RNA rebound or set point during the treatment interruption, could prolong time off ARV.

Keywords: treatment interruption; Interleukin-2; antiretroviral therapy