Structured interruptions of highly active antiretroviral therapy in cycles of 4 weeks off/12 weeks on therapy in children having a chronically undetectable viral load cause progressively smaller viral rebounds

• Published in: International journal of infectious diseases 2010-01, Vol.14 (1), p.e34-e40
• Main Authors: Palacios, Gerardo C, Sanchez, Luz M, Briones, Evangelina, Ramirez, Teresa J, Castillo, Hugo, Rivera, Lydia G, Vazquez, Carlos A, Rodriguez-Padilla, Cristina, Holodniy, Mark
• Format: Article
• Language: English
• Subjects: Acquired immunodeficiency syndrome (AIDS); Anti-HIV Agents - administration & dosage; Antiretroviral Therapy, Highly Active; Child; Cohort Studies; Drug Administration Schedule; Female; Highly active antiretroviral therapy (HAART); HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1; Humans; Infectious Disease; Lymphocyte Count; Male; Pulmonary/Respiratory; Structured treatment interruptions; Treatment Outcome; Viral Load; Withholding Treatment
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2009.03.003

Summary Objectives To evaluate the viral, immune and clinical impact of a structured treatment interruption (STI) program of highly active antiretroviral therapy (HAART) in three cycles of 4 weeks off/12 weeks on therapy in a cohort of children with HIV infection under chronic viral control. Methods Using a single-group time series experimentation design and following informed consent, the HAART of children with HIV and a chronically undetectable viral load (VL) was discontinued for 4 weeks and then restarted and continued for 12 weeks for a total of three cycles. The VL, CD4+/CD8+ lymphocytes, and clinical status were evaluated at the end of each STI and at 6 and 12 weeks after HAART was resumed. Results Four children with a median age of 10.3 years (range 6.5–11.2 years) were included in the study. Their clinical immune categories were: A1 ( n = 2), A2 ( n = 1), and B3 ( n = 1). Treatment of all four patients was with zidovudine (AZT) + lamivudine (3TC) + ritonavir (RTV). At the end of the first STI, VL was a median 214000 copies/ml (range 27400–616000), corresponding to 5.3 log10 (range 4.4–5.8). At the end of the second STI, VL was a median 72400 copies/ml (range 17800–126000) or 4.7 log10 (range 4.2–5.1), which corresponds to a rebound 0.6 log10 lower than the first. At the end of the third STI, VL was a median 28200 copies/ml (range 5370–140000) or 4.45 log10 (range 3.7–5.1), a rebound 0.85 log10 lower than the first. All rebounds were followed by a decrease in the VL to undetectable levels during the treatment periods. CD8+ T lymphocyte counts increased during viral rebounds and an initial decrease in CD4+ T lymphocyte counts was followed by a tendency to increase even exceeding CD8+ T cell counts. Only one event of transitory severe immunosuppression occurred. There were no symptoms related to the HIV infection. Conclusions The STI of HAART in cycles of 4 weeks off/12 weeks on therapy in children with chronically undetectable VL can cause progressively lower viral rebounds followed by a decrease to undetectable levels, with a low risk of severe immunosuppression and without the occurrence of symptoms related to HIV.