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

https://doi.org/10.1016/j.ijid.2009.03.003Get rights and content
Under an Elsevier user license
open archive

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.

Keywords

Structured treatment interruptions
Highly active antiretroviral therapy (HAART)
Acquired immunodeficiency syndrome (AIDS)

Cited by (0)