Comparison of Treatment Simplification by LPV/r vs Current Treatment Continuation in HIV-Infected Patients

Highly active antiretroviral therapy (HAART) has made a significant impact on the natural history of HIV-1 infection, but toxicities and complexities of therapy limit long-term efficacy, and make simpler yet effective HAART regimens highly desirable. Previous attempts to 'de-intensify' protease inhibitor (PI)-based therapy by discontinuing reverse transcriptase inhibitors (RTI) after achieving viral suppression met with failure, probably because plasma levels of most individually administered PI are too low to inhibit viral replication consistently.

Low-dose ritonavir substantially enhances lopinavir plasma levels, and lopinavir/ritonavir (LPV/r) is effective as part of a combination therapy in both naive and PI-experienced patients. Furthermore, lopinavir is known to have a high genetic barrier to selection of resistance. LPV/r monotherapy could thus have the right combination of potency, favorable pharmacokinetics, and high genetic barrier needed to suppress viral replication and prevent the selection of lopinavir resistance. Preliminary results with "maintenance"LPV/r monotherapy show interesting results but data from randomized studies are needed.

Inclusion criteria

• Age > or = 18 years
• Confirmed HIV-1 seropositivity
• Antiretroviral treatment stable since 3 months at least
• HIV-1 ARN load < 50 copies/mL since 6 months at least
• Signed consent form
• No history of treatment failure (= viral load > 1000 copies/mL) including a protease inhibitor
• No opportunistic infection in the previous 6 months

Exclusion criteria

• Neutrophils < 750/mm3
• Hemoglobin < 8 g/dL
• Platelets < 60,000/mm3
• Creatinin > 150 micromoles/L
• SGOT > 5 NUL (Normal Upper Limit)
• SGPT > 5 NUL
• Current IL-2 treatment
• HBV infection treated or not by lamivudine or tenofovir
• Pregnancy or feeding
• Enrollment in another study not compliant with KALESOLO Study group assignment