Structured Antiretroviral Treatment Interruptions in Chronically HIV-1-Infected Subjects

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 23; pp. 13288 - 13293
• Main Authors: Ortiz, Gabriel M., Wellons, Melissa, Brancato, Jason, Ha T. T. Vo, Zinn, Rebekah L., Clarkson, Daniel E., Van Loon, Katherine, Bonhoeffer, Sebastian, Miralles, G. Diego, Montefiori, David, Bartlett, John A., Nixon, Douglas F.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06.11.2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Adult; AIDS; Antiretroviral Therapy, Highly Active; Antivirals; Biological Sciences; CD4 antigen; CD4 Lymphocyte Count; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells; Drug Administration Schedule; Drug therapy; Drug Therapy, Combination; Female; Highly active antiretroviral therapy; HIV; HIV 1; HIV Antibodies - immunology; HIV Infections - drug therapy; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - therapeutic use; HIV-1 - immunology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunity; Immunology; Infections; Male; Middle Aged; Neutralization Tests; Neutralizing antibodies; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - therapeutic use; RNA; T lymphocytes; Viral Load; Viruses
• ISSN: 0027-8424; 1091-6490
• 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 µl. CD4+T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-γ-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.