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

Abstract

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 copies per ml and CD4(+) T cells >400 per microl. CD4(+) T cells, VL, HIV-1-specific 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 augmented CD8(+) T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4(+) T cell count from pre-STI level, and VL 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, and showed no enhancement of antiviral CD8(+) T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.

Figure 1

Schematic presenting schedule of structured antiretroviral treatment interruptions (STI). STI subjects underwent two 4-week-long STIs and one 12-week-long STI. Control subjects remained on HAART. Gray rectangles, STI periods; White rectangles, on HAART periods.

Figure 2

Longitudinal follow-up of HIV-1 plasma RNA levels and CD4⁺ T cell levels in eight chronically HIV-1-infected individuals undergoing STI. Time of follow-up was in weeks after initiation of first treatment interruption. HIV-1 plasma RNA, and CD4⁺ T cell counts are presented along the left and right y axes, respectively. If measurements were available, tabs on the left and right y axes represent pre-HAART baseline for HIV-1 plasma RNA level and CD4⁺ T cell count, respectively. Gray rectangles, STI periods; White rectangles, on HAART periods.