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Protease inhibitor therapy in children with perinatally acquired HIV infection
R M Rutstein1, A Feingold, D Meislich
1Division of General Pediatrics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Insights
Protease inhibitor therapy significantly improved viral load and CD4 counts in HIV-infected children. However, adverse events like renal and liver issues were noted, requiring further safety data.
Area of Science:
- Pediatric Infectious Diseases
- Antiretroviral Therapy Research
- HIV/AIDS Clinical Management
Background:
- Review of short-term outcomes and safety of protease inhibitor (PI) therapy in pediatric Human Immunodeficiency Virus (HIV) infection.
- Assessment of combination antiretroviral therapy (ART) including PIs in a cohort of pretreated HIV-infected children.
Observation:
- Retrospective chart review conducted at two urban pediatric HIV centers.
- Twenty-eight HIV-infected children received 30 PI-containing ART regimens; median age at initiation was 79 months.
- Patients had a mean of 45.5 months of prior ART exposure.
Findings:
- Twenty-six of 28 children showed significant virologic and immunologic improvement, with a mean viral load decrease of 1.90 log10 copies/mL and CD4+ lymphocyte increase of 279 x 10(6)/L.
- Eleven patients reached a viral load nadir below 400 copies/mL, with seven maintaining this for a mean of 6 months.
- Adverse events included renal side-effects (interstitial nephritis) with indinavir and elevated liver enzymes with ritonavir.
Implications:
- PI therapy offers substantial short-term benefits for heavily pretreated pediatric HIV patients.
- Significant adverse events necessitate further pharmacokinetic and safety studies for optimized pediatric ART.
- Development of alternative treatment options is crucial for children intolerant or failing current PI regimens.
Objective:
To review the short-term response and safety of protease inhibitor therapy in HIV-infected children.
Design:
Retrospective chart review of open-label protease inhibitor-containing combination therapy.
Setting:
Two urban pediatric HIV centers.
Patients:
Twenty-eight HIV-infected children were prescribed 30 protease inhibitor-containing antiretroviral therapy combinations. The median age at initiation of protease inhibitor antiretroviral therapy was 79 months. Patients had been on previous antiretroviral therapy for a mean of 45.5 months.
Results:
Of the 28 children who completed at least 1 month of therapy, 26 experienced marked virologic and immunologic improvement (mean maximal decrease in viral load 1.90 log10 copies/ml; SD, 0.8; mean maximal rise in CD4+ lymphocytes of 279 x 10(6)/l; SD, 300 x 10(6)/l). Eleven patients achieved a viral nadir of < 400 copies/ml, and seven sustained this level of viral suppression for a mean of 6 months. Indinavir use was associated with a high incidence of renal side-effects, including two patients who developed interstitial nephritis. Two patients on ritonavir experienced a significant elevation of liver enzymes.
Conclusions:
Protease inhibitor therapy was associated with substantial short-term virologic and immunologic improvement in this primarily heavily pretreated cohort, with 25% maintaining a viral load of < 400 copies/ml after 6 months of therapy. There was a significant rate of adverse events. Pharmacokinetic and safety data are needed to guide aggressive antiretroviral therapy in HIV-infected children, and further treatment options are required for those failing or intolerant to the available protease inhibitors.