Antiretroviral therapy improves thymic output in some HIV-infected children

Although the thymic function in children is adversely effected by HIV infection, it appears that function can be restored by potent antiretroviral therapy, according to a report published in the April issue of The Journal of Infectious Diseases.

Dr Daniel C. Douek, of The University of Texas Southwestern Medical Center, Dallas, and colleagues studied 9 HIV-infected children between 4 months and 12 years of age. All of the patients received multidrug regimens of antiretroviral therapy.

The researchers measured plasma viral load and CD4 and CD8 cell counts. They also measured thymus function by quantifying signal joint T-cell receptor rearrangement excision circles (sjTRECs) in the subjects’ peripheral blood. All of the children had decreased thymic function at baseline.

With treatment, Dr. Douek’s group found that 5 patients had viral load decreased to less than 400 copies/mL, while 4 children ‘had transient or incomplete suppression of viral replication.’ All the children had increases in CD4 cell counts, but they found no significant difference in CD4 cell counts between the virologic responders and the nonresponders.

‘However,’ Dr Douek’s group writes, ‘there was a difference in the recovery of sjTREC frequency between virologic responders and nonresponders. Four of the 5 virologic responders had increases in sjTREC within their peripheral CD4 T-cell pool, whereas only 1 of 4 virologic nonresponders had a sustained increase in sjTREC.’

Based on these findings, they speculate that patients who have better viral load suppression may produce ‘better quality of T-cell regeneration secondary to improved production of T cells via the thymus.’

While Dr Douek’s team points out that no difference in T-cell regeneration quality has been proven, they believe that viral suppression aids recovery of thymic function and should enhance the ‘overall T-cell reconstitution of the patient.’ Ref: J Infect Dis 2000;181:1479-1482. Source: Reuters Health. Bioavailability of once- and twice-daily regimens of didanosine in HIV-1 infected children The bioavailability of didanosine at 180 mg/m(2) once daily was compared to that at 90 mg/m(2) twice daily in 24 children with advanced human immunodeficiency virus infection. Children were studied at steady state using optimal sampling and prior pharmacokinetic parameter estimates. Relative bioavailability was 0. 95 +/- 0.49, supporting the potential clinical adequacy of once-daily dosing.

Abreu T, Plaisance K, Rexroad V et al. Antimicrob Agents Chemother 2000 May;44(5):1375-6.