PACTG P1030: LOPINAVIR/RITONAVIR IN HIV-1 INFECTED INFANTS < 6 MONTHS OF AGE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This PACTG study will help to identify an appropriate dose range of lopinavir/ritonavir (LPV/RTV) and evaluate response to therapy in infants less than 6 months of age. Lopinavir/ritonavir has shown significant antiviral activity and tolerability in clinical trials in adults and children >6 months of age. In antiretroviral-nanve HIV-infected adults, the combination of LPV 400 mg/RTV 100 mg BID produces a mean LPV trough concentration (Ctrough) which is more than 50 times higher than the EC50 of wild-type HIV. In comparison, the Ctrough/EC50 ratio in the presence of human serum for currently available protease inhibitors (PIs) is <4. This is a Phase I/II, open-label, dose finding study with a sample size of 12 HIV-infected infants older than 14 days and less than 6 months with at least three of the infants being less than 6 weeks. The regimen is Lopinavir 300mg/m2 / Ritonavir 75 mg/m2 / BID and 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment will continue until 24 months after the last subject is enrolled. The study will evaluate the LPV/RTV dose requirements to provide systemic exposure similar to that which has been shown to be safe and effective in older children and adults. It will also determine the short-term and long-term safety and tolerability of LPV/RTV initiated in infants less than 6 months old as part of a regimen including (NRTIs).