Sequential HIV Therapy in Treatment Resistant HIV-1 Infected Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Sequential HAART in Treatment Resistant HIV-1 Infected Patients

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Standard Continuous Highly Active Antiretroviral Therapy (HAART)
* Drug: Rapidly Cycled HAART


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Continuous triple-class therapy<br>Patients will be treated with a regimen containing antiretroviral agents from 3 different classes | Drug: Standard Continuous Highly Active Antiretroviral Therapy (HAART)<br> <br> |
| Experimental: Alternating therapy<br>Patients will be assigned to weekly alternating dual-class regimen | Drug: Rapidly Cycled HAART<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma HIV-1 RNA load |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the genotype of the dominant quasispecies |  | 12 weeks | 
| Replicative fitness of the dominant quasispecies |  | 12 weeks | 
| Changes in CD4+ and CD8+ cell counts |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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resistance, HIV-1, HAART, sequential HAART, salvage therapy, Treatment Experienced