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

Condition	Intervention	Phase
HIV-1	Drug: standard continuous Highly Active AntiRetroviral Therapy  Drug: rapidly cycled Highly Active AntiRetroviral Therapy	Phase IV

Further Study Details: 

Primary Outcomes: Changes in plasma HIV-1 RNA load.
Secondary Outcomes: - Changes in the genotype of the dominant quasispecies; - Replicative fitness of the dominant quasispecies; - Changes in CD4+ and CD8+ cell counts
Expected Total Enrollment:  12

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 anti-retroviral 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 patients 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00128908

Radjin Steingrover, MD      +31205667188    r.steingrover@amc.uva.nl

Netherlands, NH
      HIV outpatient clinic, Academic Medical Center, Amsterdam,  NH,  1105AZ,  Netherlands

Study chairs or principal investigators

Joep MA Lange, MD PhD,  Study Chair,  Academic Medical Center   
Ferdinand Wit, MD PhD,  Study Director,  Academic Medical Center   

Study ID Numbers:  05IAT0061; 2004040 - Dutch AIDS Fund
Last Updated:  August 9, 2005
Record first received:  August 8, 2005
ClinicalTrials.gov Identifier:  NCT00128908
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
ClinicalTrials.gov processed this record on 2005-08-23