Safety and Effectiveness of Lopinavir/Ritonavir in HIV Infected Infants

A Phase I/II Study of Lopinavir/Ritonavir in HIV-1 Infected Infants Less Than 6 Months of Age

The purpose of this study is to find out if the drug lopinavir/ritonavir (LPV/RTV) is safe and well tolerated in HIV infected infants. This study will also determine the most effective dose of LPV/RTV for infants.

LPV/RTV has shown significant antiviral activity and tolerability in clinical trials in adults and children over 6 months of age. LPV/RTV has been approved by the FDA to treat older children and adults with HIV. Data for children under 6 months, however, have not been available. LPV/RTV has not been approved for infants less than 6 months old, and the appropriate dose for young infants is not known. Dosing guidelines are needed for young infants, most of whom are in the early stages of primary infection. This study will help identify an appropriate dose range of LPV/RTV and evaluate response to therapy in infants less than 6 months of age. The study will also evaluate whether early therapy allows normal development of the immune system.

Infants between 14 days and 6 months of age will receive LPV/RTV in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs) chosen by their physicians. Twelve-hour pharmacokinetic sampling is performed on Day 14 of drug treatment and when the patient reaches 12 months of age. Patients will undergo a physical exam, medical history assessment, and blood collection at selected study visits. Study visits will occur every 2 weeks for the first 8 weeks, then every 4 weeks until the end of the first year of the study. Study visits during the second year will be every 12 weeks until the end of the study. The parent or guardian will be contacted by phone every 6 weeks to monitor adverse drug effects. Participants between the ages of 6 weeks but less than 6 months old will be followed for 96 weeks after the enrollment of the last participant. Participants between the ages of 14 weeks but less than 6 weeks will be followed for 48 weeks after the enrollment of the last participant.

Inclusion Criteria

• HIV infected
• Viral load greater than 10,000 copies/ml within 30 days prior to study entry
• Weigh more than 5.5 lbs at the time of enrollment
• Agree to take 2 nucleoside reverse transcriptase inhibitors (NRTIs) in addition to LPV/RTV
• Have consent of parent or guardian willing to provide signed informed consent and to have the infant followed at a PACTG site

Exclusion Criteria

• Currently taking a nonnucleoside reverse transcriptase inhibitor or protease inhibitor (PI) while on study
• Previously used LPV/RTV. Patients who were treated previously with other PIs are not excluded. Prior or concurrent maternal treatment with LPV/RTV is not excluded.
• For patients less than 6 weeks old at time of enrollment, less than 34 weeks gestation at delivery OR for patients 6 or more weeks old at time of enrollment, less than 32 weeks gestation at delivery
• Any laboratory toxicity of Grade 3 or greater. Hyperlipasemia of Grade 2 or higher is also excluded.
• Newly diagnosed acute opportunistic or serious bacterial infection requiring therapy at the time of enrollment
• Chemotherapy for active cancer
• Certain medications
• Any other clinically significant conditions, other than HIV infection, that would interfere with the study