Clinical trial NCT00128908: Sequential HIV Therapy in Treatment Resistant HIV-1 Infected Patients
Official title: Sequential HAART in Treatment Resistant HIV-1 Infected Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV-1
HAART
sequential HAART
resistance
salvage therapy
Treatment Experienced
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Dutch AIDS Fund
First posted: 2005-08-10
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Changes in plasma HIV-1 RNA load
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes in the genotype of the dominant quasispecies
timeFrame: 12 weeks
measure: Replicative fitness of the dominant quasispecies
timeFrame: 12 weeks
measure: Changes in CD4+ and CD8+ cell counts
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: HIV Outpatient Clinic, Academic Medical Center
state: NH
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Joep MA Lange, MD PhD
role: STUDY_CHAIR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Ferdinand Wit, MD PhD
role: STUDY_DIRECTOR
References: