ABSTRACT:
To test the strategy of an immune-based therapy using cyclic interruptions of treatments, we addressed the safety of this approach, the dynamics of viral load (VL) rebound and response after reintroducing the same therapy and the immune system changes in a cohort of eight consecutive patients in very early stages with chronic HIV-1 infection who discontinued highly active antiretroviral therapy after 1 year of successful treatment when therapy was interrupted (day 0). All eight patients had a sustained plasma VL below 20 copies/mL.
Medical visits were scheduled at baseline and days 0, 3, 7, 14, 21, 28 and monthly thereafter. The same antiretroviral therapy was initiated when plasma viral load became detectable. At baseline, plasma VL was below 5 copies/mL in five of eight cases, cerebrospinal fluid (CSF) VL below 20 copies/mL in all cases and tonsillar tissue viral load below40 copies/mg of tissue in all five patients with accessible tonsils. A rebound in plasma viral load was detected in all cases from day 2 to day 27 with a mean ±SD doubling time of 2.1±0.89 days. Three out of eight patients achieved a peak viral load higher (>0.5 log10) than baseline value before starting therapy. Mutations associated with resistance to stavudine and lamivudine were not detected.
During the period of viral rebound (at 0 and 25 days) percentage of CD8+CD28+ lymphocytes decreased (from a mean ±SD 45±14 to 36±7, P=0.07, and from 54±13 to 39±12, P=0.027, respectively) and percentage of CD8+CD38+ increased (from a mean ±SD 56±7 to 66±10, P= 0.05). SI index of phytohemagglutinin (PHA) and CD3 (at 0 and 25 days) decreased from a mean ±SD 33±31 to 15±21, P=0.1 and from 25±22 to 8±13, P=0.03, respectively in the five patients with a plasma viral load at day 0 of<5 copies/mL. However, SI index of PHA and CD3 did not change in the patients with a plasma viral load at day 0 between 5 and 20 copies/mL. Viral load dropped again below 20 copies/mL and CD4 T cell counts increased to at least day 0 levels (day of first interruption of therapy) in all patients after 1 month of restarting the same antiretroviral regimen. Six months later, all patients remained below 20 copies/mL and a second interruption was performed.
Discontinuation of highly active antiretroviral therapy after 1 year of successful treatment are followed by a quick rebound. In the patients with viral load below 5 copies/mL the sequence of immunological and virological events associated with an acute infection are reproduced after interruption of treatment. The response to the antiretroviral treatment is very quick, The dynamics of viral load rebound and the immune system changes, including proliferative response to HIV-1 antigens, after the second interruption will be reported.
