TY - JOUR
T1 - Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents
AU - Soh, Chang Heok
AU - Oleske, James M.
AU - Brady, Michael T.
AU - Spector, Stephen A.
AU - Borkowsky, William
AU - Burchett, Sandra K.
AU - Foca, Marc D.
AU - Handelsman, Edward
AU - Jiménez, Eleanor
AU - Dankner, Wayne M.
AU - Hughes, Michael D.
N1 - Funding Information:
The study was funded by the US National Institutes of Health. Scientific staff from the National Institutes of Health are involved in the design and conduct of PACTG protocol 219, but they were not involved in the analysis or interpretation of data, the writing of this report, or the decision to submit it for publication.
PY - 2003/12/20
Y1 - 2003/12/20
N2 - Background: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment. Methods: The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes. Findings: Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and ≥25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and ≥10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values. Interpretation: Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.
AB - Background: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment. Methods: The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes. Findings: Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and ≥25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and ≥10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values. Interpretation: Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.
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U2 - 10.1016/S0140-6736(03)15098-2
DO - 10.1016/S0140-6736(03)15098-2
M3 - Article
C2 - 14697803
AN - SCOPUS:9144258622
SN - 0140-6736
VL - 362
SP - 2045
EP - 2051
JO - The Lancet
JF - The Lancet
IS - 9401
ER -