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

Ortiz GM, Wellons M, Brancato J, Vo HT, Zinn RL, Clarkson DE, Van Loon K, Bonhoeffer S, Miralles GD, Montefiori D, Bartlett JA, Nixon DF
Proc Natl Acad Sci U S A. 2001 98 (23): 13288-93

PMID: 11687611 · PMCID: PMC60863 · DOI:10.1073/pnas.221452198

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.

MeSH Terms (17)

Adult Antiretroviral Therapy, Highly Active CD4 Lymphocyte Count CD8-Positive T-Lymphocytes Drug Administration Schedule Drug Therapy, Combination Female HIV-1 HIV Antibodies HIV Infections HIV Protease Inhibitors Humans Male Middle Aged Neutralization Tests Reverse Transcriptase Inhibitors Viral Load

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