Sequential HIV Therapy in Treatment Resistant HIV-1 Infected Patients

Phase 4

Terminated

• Conditions: HIV Infections
• Interventions: Drug: Standard Continuous Highly Active Antiretroviral Therapy (HAART); Drug: Rapidly Cycled HAART

• Registration Number: NCT00128908
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

This is an open label, crossover pilot study to explore the safety and efficacy of a rapid cycling regimen of antiretroviral combination therapy in HIV-1 infected patients with virus harboring genotypic resistance to at least three classes of antiretroviral therapy.

Detailed Description

Mathematical modeling has suggested that cyclic use of antiretroviral therapy can be an effective strategy in lowering viral load in HIV-1 infected patients when regular triple drug combinations have lost efficacy due to the emergence of HIV resistance mutations.

This is an open label, crossover pilot study to explore the safety and efficacy of a rapid cycling regimen of antiretroviral combination therapy in HIV-1 infected patients with virus harboring genotypic resistance to at least three classes of antiretroviral therapy.

The objectives are to study the feasibility, safety and efficacy of sequential combination therapy in HIV-1 infected patients with virus harboring genotypic resistance to at least three classes of antiretroviral agents and who currently have no adequate treatment options available.

This is an open-label, crossover, pilot study. Patients that fail their current regimen, and who currently have no adequate treatment options left, will be randomized to start either an alternating triple combination, or to start a continuous quadruple regimen of drugs. After 6 weeks, patients will crossover from either strategy to the other strategy for another 6 weeks. Each period is preceded by an interruption of all antiretroviral therapy for 4 weeks. In the study period when regimens are alternated, two combinations of three drugs with the least possible cross-resistance will alternate every week.

Study Timeline

• Study First Submitted: 2005-08-08
• Study First Submitted QC: 2005-08-08
• Study First Posted: 2005-08-10
• Study Start: 2005-09
• Primary Completion: 2007-01
• Study Completion: 2007-01
• Status Verified: 2009-09
• Last Update Submitted: 2009-09-14
• Last Update Posted: 2009-09-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

• HIV-1 infected patients
• At least 18 years of age
• Males or non-pregnant, non-lactating females
• Documented virological treatment failure on at least 3 classes of antiretroviral drugs
• No adequate antiretroviral therapy possible with currently available antiretroviral agents
• Virological treatment failure is defined as plasma HIV-1 RNA levels > 5000 while taking at least three different antiretroviral drugs

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Continuous triple-class therapy	Standard Continuous Highly Active Antiretroviral Therapy (HAART)	Patients will be treated with a regimen containing antiretroviral agents from 3 different classes
Alternating therapy	Rapidly Cycled HAART	Patients will be assigned to weekly alternating dual-class regimen

Primary Outcome Measures

Name	Time	Method
Changes in plasma HIV-1 RNA load	12 weeks

Secondary Outcome Measures

Name	Time	Method
Changes in CD4+ and CD8+ cell counts	12 weeks
Replicative fitness of the dominant quasispecies	12 weeks
Changes in the genotype of the dominant quasispecies	12 weeks

Trial Locations

Locations (1)

HIV Outpatient Clinic, Academic Medical Center; 🇳🇱 Amsterdam, NH, Netherlands