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Structured Treatment Interruption in Chronically HIV-1 Infected Patients after Long-Term Viral Suppression L. RUIZ*, J. MARTINEZ-PICADO, J. ROMEU, E. NEGREDO, A. TULDRĄ, C. TURAL, and B. CLOTET.
Univ. Hosp. Germans Trias i Pujol, Barcelona, Spain Objective: To assess virological and immunological changes during structured treatment interruption (STI) in HIV-1 chronically infected patients (pts) after long-lasting virus suppression.
Methods: Twenty-five HIV-infected pts with at least 2-years-long virus suppression and a CD4/CD8 ratio>1 were randomized to continue with the prior antiretroviral treatment (ART) (n=13;Group1) or to interrupt ART during a maximum period of 30 days (d) or until the viral load (VL) increases > 3,000 c/ml (n=12; Group2). The same prior ART was resumed after STI in pts from Group 1 for 90 d until the next cessation treatment. Kinetics of plasma viral rebound were evaluated every 2 d. during the two treatment interruption periods in Group 2 and every 3 mo. in Group 1. Flow cytometry and cell proliferation assays were performed before and after the 1st STI period. Genotypic resistance was assessed at the time of treatment resumption.
Results: There was no VL rebound in 2 pts after 30 d. of the 1st STI whereas only 1 pt maintained VL<20 c/mL for the same period at the 2nd STI. In the remaining pts, VL became detectable (>20 c/ml) for a median of 14 and 15 days, at the 1st and the 2nd STI periods, respectively. VL rose exponentially with a mean t1/2 of 1.6 d. and 2.2 d. at the 1st and the 2nd interruption periods. ART was successfully resumed in all pts. No resistance-conferring mutations were selected during the STI interval. The percentage in CD4+ and CD8+ did not vary during the STI period. However, the expression of CD38 on CD8+ T cells increased significantly in response to viral rebound. A lower CD4/CD8 ratio was associated with a flatter slope (p=0.02). Four pts gained helper T-cell responses to recall antigens, 2 of whom developed HIV-specific response to p24 at the 1st STI interval. Only helper T-cell responses to recall antigens were maintained at BL of the 2nd STI.
Conclusions: STI is not associated to reductions in CD4+ or clinical complications in our pts after 2 years of effective plasma VL suppression. VL rebounds in most but not all pts. Viremia can be effectively controlled upon ART reintroduction. HIV-specific helper T-cell responses may require subsequent cycles of STI to keep viral replication under control.
Key Words: HIV T-cell responses, Treat. Interruption, Viral load
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