Clinical trial NCT00344487
Conditions: HIV
Sponsor: University of Maryland, Baltimore
Start date: 2005-12-01; Completion date: 2009-09-01
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
To explore the hypothesis that the use of Lopinavir/ritonavir will be associated with improved CD4 immune reconstitution in volunteers who fail to demonstrate a significant CD4 cell increase (while on their first antiretroviral treatment regimen) despite sustained viral suppression by a non-Lopinavir/ritonavir-containing regimen

Detailed description:
This is an open-labeled, non-randomized exploratory trial in selected volunteers who meet the stated enrollment criteria. This study will assess the impact of Lopinavir/ritonavir on CD4 immune reconstitution. All volunteers must have been on antiretroviral therapy with sustained viral load suppression of \< 400 copies/mL for at least 24 months (or, HIV-1 RNA \< 400 copies/mL for 12 months, during which HIV-1 RNA was \< 50 copies/mL for 6 months prior to screen). Despite induction of viral suppression, all volunteers must have demonstrated limited post-antiretroviral CD4 increase.

Lopinavir/ritonavir will be substituted for one of the 3 ARV drugs in the current (baseline) antiretroviral treatment regimen. Lopinavir/ritonavir will be substituted for any of the following: 3rd NRTI, an NNRTI, a PI or a boosted PI, while the nucleoside backbone will remain the same. If the subject is currently on a three-drug nucleoside/nucleotide plus a 4th anchor drug such as a NRTI, NNRTI, PI or boosted PI regimen, the triple nucleoside will remain constant and only the anchor drug is to be substituted with Lopinavir/ritonavir. Patients on 2 NRTIs with an NNRTI and a PI combination will not be allowed in the study.

Patients will be evaluated frequently, to include physical examination, assessment for the development of AIDS-defining conditions, hematology, chemistry, lipid profile, CD4 CD8 cell counts, plasma HIV-1 RNA ultrasensitive, and assessment of adverse events. If HIV-1 RNA becomes detectable, this will be repeated for confirmation with 2 weeks. HIV genotyping and phenotyping will be performed on patients who demonstrate repetitive plasma viral load levels of \> 1,000 copies/mL.

An assessment of memory and naïve T cell response to antiretroviral regimen change will be performed in this study.

Dose and dose selection Lopinavir/ritonavir is also approved for once a day dosing. The dose of lopinavir/ritonavir (Kaletra) for this study will be 400/100mg. BID or 800/200mg. qd. New tablet formulation no longer requires that lopinavir/ritonavir be taken with food. We will give the volunteer the option for once a day dosing or BID dosing of Kaletra. However, those switching from an NNRTI to Kaletra will initially be placed on BID dosing of Kaletra, and allowed to switch to once-a-day dosing of Kaletra after 4 weeks on study drug.

Arms: arm 1: lopinavir/ritonavir (Kaletra)400/100mg tablets by mouth twice a day for 48 weeks.
Interventions: intervention 1: Lopinavir/Ritonavir
Intervention descriptions: intervention 1: Dosing of Kaletra will be per package insert and BID with food. A three-drug standard of care antiretroviral regimen will be used in this study. Subjects will enter the study already on an effective, virally-suppressive treatment regimen. One of these drugs will be substituted for Lopinavir/ritonavir (Kaletra®). However, the nucleoside/nucleotide backbone drugs that the subject is already on will remain the same.

Protocol documents: