Timed-cycle STI have not been proven to be safe in the short term. Although CD4-guided STI strategy has reported favorable outcomes in the short term, the long-term safety, efficacy and tolerability of this strategy has not been fully investigated. Based on the studies we reviewed, the evidence to support the use of timed-cycle STI and CD4-guided STI cycles as a standard of care in the management of chronic suppressed HIV infection is inconclusive.
Acute human immunodeficiency virus replication causes a rapid and persistent impairment of Vgamma9Vdelta2 T cells in chronically infected patients undergoing structured treatment interruption.
T cells expressing Vgamma9Vdelta2 display lytic and proliferative responses against human immunodeficiency virus (HIV)-infected cells and release antiviral soluble factors. Chronic HIV-positive patients have deep changes in the composition and function of the circulating gammadelta T cell pool that are restored by highly active antiretroviral therapy (HAART). gammadelta T cells were analyzed during the rapid plasma HIV RNA rebound in HIV-infected patients undergoing structured treatment interruption (STI). A loss in circulating Vgamma9Vdelta2 T cells was observed, indicating that acute HIV replication may influence Vgamma9Vdelta2 homeostasis. These cells were lost among CD45RA(-)CD27(-) Vgamma9Vdelta2 T cell effectors, and a significant unresponsiveness, measured as antigen-driven interferon-gamma production, was observed during STI. After HAART resumption and consequent inhibition of HIV replication, Vgamma9Vdelta2 T cell reactivity was restored both quantitatively and functionally. These observations indicate that Vgamma9Vdelta2 T cells are activated early after active HIV replication but are rapidly lost when viremia is not controlled.