Ritonavir-boosted Lopinavir Monotherapy

Treatment Outcomes and Plasma Level of Ritonavir-boosted Lopinavir Monotherapy Among HIV-infected Patients Who Had Non-nucleoside Reverse Transcriptase Inhibitor (NRTI) and NNRTI Failure: A Pilot Study

To assess 48-week treatment responses, tolerability, and steady-state minimum plasma concentrations of ritonavir-boosted lopinavir monotherapy for salvage therapy in HIV-1 infected patients who failed antiretroviral regimens containing NRTI and NNRTI.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: lopinavir/ritonavir soft gel capsule

Detailed Description

Currently, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) is widely prescribed as an initial therapy for treatment naïve HIV-infected patients, particularly in many resource-constrained countries. However, in patients who have delayed detection of treatment failure in this setting, the virus is often resistant to most existing nucleoside reverse transcriptase inhibitors (NRTIs) and NNRTIs even failing from the first regimen. As a consequence, constructing the potent salvage regimens that combined 2 or 3 fully active drugs from existing drug classes is often impossible in many resource-constrained countries where new agents, such as integrase inhibitor and chemokine receptor antagonist, are neither available nor affordable. Nevertheless, the goal of attaining undetectable plasma HIV-1 RNA is remain mandatory. To date, several clinical studies derived from the western countries that included 2 or more active drugs clearly demonstrate effective therapeutic strategies for antiretroviral (ARV)-experienced HIV-1 infected patients. Hence, using ritonavir-boosted protease inhibitor in a salvage therapy was considered to be an option in the resource-constrained countries and the limitations of remaining active NRTIs usually lead to ritonavir-boosted protease inhibitor monotherapy as a salvage regimen.

Among several previous reports using ritonavir-boosted protease inhibitor, ritonavir-boosted lopinavir monotherapy has been extensively studied so far. Different strategies of ritonavir-boosted lopinavir monotherapy have been explored; however, most related clinical trials studied this regimen as either a treatment simplification strategy or induction therapy in treatment-naïve patients. A strategy to use ritonavir-boosted lopinavir monotherapy as a salvage regimen is not available. On the other hand, previous studies showed that continuation of lamivudine after emerging of the M184V mutation had somewhat benefit on immunological response and clinical progression in patients who had limited options of salvage regimens. Moreover, there is neither additional any other mutation nor increase resistance to other antiretroviral drugs. Thus, this is the reason why we added lamivudine to decrease viral fitness in the study regimen. The objective of this study was to assess 48-week treatment responses, tolerability, and steady-state minimum plasma concentrations of ritonavir-boosted lopinavir monotherapy for salvage therapy in HIV-1 infected patients who failed antiretroviral regimens containing NRTI and NNRTI.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HIV-1 infected patients >18 years of age,
2. failed NNRTI-based antiretroviral therapy with M184V, thymidine analogue mutations (TAMs) and NNRTI-associated mutations
3. had plasma HIV-1 RNA >1,000 copies/mL.

Exclusion Criteria:

1. Had a history of exposure to protease inhibitor
2. Receipt a medication that has drug-drug interactions with lopinavir.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lopinavir/ritonavir	Drug: lopinavir/ritonavir soft gel capsule; Ritonavir-boosted lopinavir in soft gel formulation at 400/100 mg and lamivudine at 150 mg were given twice daily.; Other Names: Kaletra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess 48-week treatment responses of ritonavir-boosted lopinavir (LPV/r) monotherapy as salvage regimen.	48 weeks

Collaborators and Investigators

• Sponsor: Bamrasnaradura Infectious Diseases Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: October 27, 2009
• First Submitted That Met QC Criteria: October 27, 2009
• First Posted (Estimate): October 28, 2009

Study Record Updates

• Last Update Posted (Estimate): November 11, 2011
• Last Update Submitted That Met QC Criteria: November 10, 2011
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Treatment experienced; HIV-1 RNA
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir
• Other Study ID Numbers: 4/2551