Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy

Background: This study addresses the dynamic of viral load rebound and immu ne system changes in a cohort of eight consecutive HIV-l-infected patients in very early stages fall the patients were taking highly active antiretrov iral therapy (HAART} and were recruited in the coordinating center from a l arger study] who decided to discontinue HAART after 1 year of treatment and effective virologic response. The safety of this procedure and the outcome with reintroduction of the same treatment was also investigated. Methods: Plasma, cerebrospinal fluid (CSF), and lymphatic tissue viral load s were measured at baseline; lymphocyte immunophenotyping and CD4 lymphocyt e proliferative responses to mitogens and specific antigens were assessed. The same antiretroviral therapy was reintroduced as soon as plasma viral lo ad became detectable (above 200 copies/ml). Results: At day 0, plasma viral load was below 20 copies/ml in all eight pa tients land below 5 copies/ml in five of eight patients). A rebound in plas ma viral load was detected in all patients from day 3 to day 31 with a mean doubling time of 2.01 (SE 0.29) days. Three out of eight patients achieved a peak plasma viral load at least 0.5 log,, above baseline, pretreatment v alues. Mutations associated with resistance to reverse transcriptase or pro tease inhibitors were not detected. After 31 days off therapy, CD4 lymphocy tes decreased [mean 45% (SE 4) to 37% (SE 3); P = 0.04], CD8+CD28+ lymphocy tes decreased [mean 59% (SE 5) to 43% (SE 4); P = 0.03], and CD8+CD38+ lymp hocytes increased [mean 55% (SE 3) to 66% (SE 4); P = 0.009]. Mean stimulat ion indices of lymphocytes treated with phytohemagglutinin (PHA) and CD3 de creased from day 0 to day 31 from 34% (SE 8) to 17% (SE 9) (P = 0.06) and f rom 24% (SE 8) to 5% (SE 2) (P = 0.02), respectively. These changes were ma inly contributed by the group of five patients with plasma viral load below 5 copies/ml at day 0. Viral load dropped below 20 copies/ml in all patient s after 1 month of restarting the same antiretroviral regimen. Conclusions: Discontinuation of HAART after 1 year of successful treatment is followed by a rapid rebound of viral load; this rapidly returns to undet ectable levels following reintroduction of the same treatment. In patients with more effective control of virus replication (viremia below 5 copies/ml ), discontinuation of treatment was associated with more severe impairment of immunologic parameters. (C) 1999 Lippincott Williams & Wilkins.