291   HIV Dynamics and HIV- Specific CD8⁺T Cells Response after Three Structured Treatment Interruptions (STI) of Antiretroviral Treatment (ART) in Chronic HIV-Infected Patients.

L. Ruiz*¹, G. Carcelain², J. Martínez-Picado¹, S. Frost³, S. Marfil¹, R. Paredes¹, J. Romeu¹, K. Morales-Lopetegi¹, B. Autran², and B. Clotet¹.
¹Lluita contra la SIDA Fndn. & and IrsiCaixa Fndn., Badalona, Spain;²Hosp. Pitié-Salpêtrière, Paris, France; and³Ctr. for HIV Res., Edinburgh, UK.

Background:Our objective was to evaluate whether re-exposure to HIV could boost HIV-specific immunity and limit HIV replication in patients (pts) with chronic HIV-1 infection after long-lasting virus suppression.

Methods:HIV⁺pts with at least 2-year-long virus suppression and a CD4/CD8 ratio >1 were randomized to continue with the prior ART (noninterrupters; n = 14) or to interrupt ART (interrupters; n = 12) during a maximum period of 30 days (d) or until the plasma viral load (pVL) increased >3,000 c/ml. ART was resumed after STI cycles in interrupter pts for 90 d.

Results:After 3 STIs (interrupter pts), in 10/12 pts a rebound of pVL was observed in all three treatment interruptions. The plasma virus doubling time (td) was lower during the 2nd and 3rd STI (1.94 d and n1.88 d, respectively) than td in the 1st STI (1.41 d). An analysis of a model fit revealed that pVL appeared to be reaching a new viral set point. In addition, the AUC (total viral replication) was lower in the 3rd STI (median = 36.9 log RNA copies/d) than in the 2nd in all pts (median decrease = 11.6 log RNA copies/ml per d, P <0.001). The percentage in CD4 and CD8 did not significantly vary during the STIs. A substantial increase in HIV-specific CD8 cell frequencies was produced in 5/12 pts. A weak p24-specific Th response was developed in 5/12 pts but disappeared rapidly.

Conclusions:Our results show that the lower virus AUC occurring in the last STI may indicate an immune control of HIV-1. This finding was further supported by a significant increase in doubling time of pVL at the 2nd and 3rd STI compared with that in the 1st STI and by a predicted decrease in viral set point at the 3rd STI. STI was not associated with reductions in CD4 or clinical complications. However, the burst of virus production in each STI stimulated HIV-specific effector CD8 T-cells in 42% of our chronically HIV⁺pts. Additional repeated STIs may develop for chronically HIV⁺pts a substantial and maintained virus-specific T-cell responses allowing a longer treatment cessation.