Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects

The risks and benefits of structured treatment interruption (STI) in HIV-1- infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) < 400 co pies per ml and CD4(+) T cells > 400 per mul. CD4(+) T cells, VL, HIV-1-spe cific neutralizing antibodies, and IFN-gamma -producing HIV-1-specific CD8( +) and CD4+ T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in aug mented CD8+ T cell responses in all eight STI subjects (P = 0.003), maintai ned while on HAART up to 22 weeks after STI, and augmented neutralization t iters to autologous HIV-1 isolate in one of eight subjects. However, signif icant decline of CD4(+) T cell count from pre-STI level, and VIL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively) . CD4(+) T cell counts were regained on return to HAART. Control subjects ( n = 4) maintained VL < 400 copies per ml and stable CD4(+) T cell counts, a nd showed no enhancement of antiviral CD8(+) T cell responses. Despite incr eases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.