Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression

Objective: To investigate the virological and immunological impact of a str uctured treatment interruption (STI) in a cohort of HIV-1 chronically infec ted patients with a further long-lasting effective virus suppression. Methods: Twelve HIV-1 chronically infected adults who had maintained viral suppression (< 20 copies/ml) for more than 2 years, as well as a CD4 :CD8 r atio > 1 for a median time of 22 months, were included in the study. Partic ipants interrupted their antiretroviral treatment during a maximum period o f 30 days or until a viral load rebound > 3000 copies/ml was detected. The same prior antiretroviral regimen was resumed after STI. Kinetics of plasma viral rebound was evaluated every 2 days during the treatment interruption period. Flow cytometry and cell proliferation assays were performed before and after STI. Genotypic resistance was assessed at the time of treatment resumption. Results: No adverse events occurred during the interruption period. In two patients no viral rebound was detected after 30 days of treatment interrupt ion. In the remaining 10 patients, viral load became detectable (> 20 copie s/ml) at a median time of 14 days after treatment interruption. Afterwards, viral load increased exponentially with a mean t(1/2) of 1.6 days. Treatme nt was successfully resumed in all patients. No resistance-conferring mutat ions associated with the pre-interruption antiretroviral regimen were detec ted. The percentage of CD4 and CD8 lymphocytes did not vary during the STI period; however, the level of expression of T-cell activation antigen CD38 on CD8 T cells increased significantly in response to viral rebound. Four p atients gained T-helper cell responses to recall antigens (tuberculin and t etanus toroid), two of who developed an HIV-specific response to p24. Conclusions: STI in chronically HIV-l-infected patients is not associated w ith reductions in CD4 T lymphocytes or to clinical complications in this gr oup of patients after 2 years of effective plasma viral suppression. Viral load rebounds in most but not all patients, without evidence of selection o f resistance-conferring mutations. Thereafter, viraemia can be effectively controlled by antiretroviral agent reintroduction. HIV-specific T-helper ce ll responses may be achieved after one cycle of treatment interruption sugg esting some degree of immune-stimulation. These data do not discard consecu tive cycles of STI as a therapeutic strategy to boost HIV-specific immunity in order to maintain viral replication under effective control. (C) 2000 L ippincott Williams & Wilkins.