Multicenter Pilot Study To Define The Marker As An Alternate For Tropism Assay

Phase 1

Terminated

Conditions: HIV Infections

Interventions: Drug: maraviroc
Procedure: Trofile Assay and HIV RNA quantification assay

Registration Number: NCT00496782

Lead Sponsor: ViiV Healthcare

Brief Summary: The purpose of this pilot study is to determine whether there is a correlation between viral load reduction (at Day 4, 7 or 14) following a short course (14 days) of Maraviroc added to a failing regimen, and the R5 result of the TrofileTM assay at screening.

Detailed Description: The study A4001060 has been discontinued on April 22, 2008. A review of the poor rate of enrollment has projected difficulties in completing the study in a timely manner, despite the best efforts by the sponsor and the sites. Given the difficulties encountered in this pilot study and the need to conduct an even larger confirmatory study, the decision to discontinue the study has therefore been made. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

Inclusion Criteria

≥ 16 years of age (or minimum adult age as determined by local regulatory authorities or as dictated by local law) at the screening visit.
Have an HIV RNA ≥ 1000 copies/mL, at screening.
Subjects receiving another investigational antiretroviral compound through participation in a phase 3 or 4 clinical study are eligible to participate in this trial provided.
That the 2 investigational agents are required to offer the subject a regimen with 2 or 3 active antiretroviral drugs (i.e. one or fewer approved treatment is available to the subject due to prior resistance or intolerance),
Neither protocol prohibits the use of the other antiretroviral agent, AND the dosing of the two agents when used together is known AND a letter from the Pfizer clinical pharmacologists for maraviroc identifies the dose of maraviroc to be used with other investigational agents.
Based on screening genotypic resistance testing results the subject must be able to receive at least 3 active drugs other than maraviroc in the new OBT. This is defined as:
Having three drugs considered susceptible by genotype interpretation (if etravirine will be used, fewer than 3 etravirine resistance mutations will be taken as etravirine susceptibility); or,
Having two drugs considered susceptible by genotype interpretation (if etravirine will be used, fewer than 3 etravirine resistance mutations will be taken as etravirine susceptibility) and be willing to include raltegravir in the OBT not having used raltegravir in the past.

Exclusion Criteria

Potentially life threatening (Grade 4) laboratory abnormality or medical condition.
Severe hepatic impairment (Child-Pugh classification B or C).
End stage renal disease or other disease states requiring dialysis therapy.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single	Trofile Assay and HIV RNA quantification assay	-
Single	maraviroc	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) With R5 & Non-R5 Tropism Results From the Trofile(tm) Assay	Baseline, Day 4, 7, 14	Spearman's correlation coefficient to assess percentage of participants achieving HIV-1 RNA with tropism

Secondary Outcome Measures

Name	Time	Method
Change in Detectable Resistance (Genotype) and Susceptibility (Phenotype) to Drugs in the Regimen From Screening	Screening (Day -21), Baseline (Day 0), Day 14 (after addition of MVC to a failing regimen), Week 24, and time of Virologic Failure.	Change in detectable resistance (genotype) and susceptibility (phenotype) to drugs in the regimen from Screening
Subjects Achieving HIV-1 RNA <400 Copies/mL	Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24	Number of Subjects Achieving HIV-1 RNA \<400 Copies/mL at each time point
Time to Virologic Failure	Baseline up to Week 24	For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA \> 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification \[LOQ\]); 2. Experiencing a \> 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline \> 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA \>1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Change in Lymphocyte Subset CD4 From Baseline	Day 1 (Baseline), Day 7, 14, 28 and Weeks 24	Calculated average of CD4 at Day 7, 14, 28 and Week 24 minus CD4 at Day 1
Change in Detectable Tropism From Screening	Screening (Day -21 to 0), Baseline.	Number of subjects who switch their tropism status from screening to Baseline
Change in Lymphocyte Subsets; CD4 and CD8 From Screening.	Screening (Day -14 to 0), Day 1.	Calculated avergae of {CD4 or CD8 at Day 1 - CD4 or CD8 at Screening}
Subjects Achieving HIV-1 RNA <50 Copies/mL	Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24	Number of Subjects Achieving HIV-1 RNA \<50 Copies/mL at each time point
Subjects With Virologic Failure	Baseline up to Week 24	For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA \> 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification \[LOQ\]); 2. Experiencing a \> 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline \> 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA \>1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Change in Detectable Tropism From Baseline	Baseline, Day 15 and Week 24/End of Study/Discontinuation	Number of subjects who switch their tropism status from Baseline to Days 7, 14, and Week 24/End of Study(EOS)/Discontinuation
Number of Subjects With Susceptibility to Maraviroc	Screening (Day -21 to 0), Day 14, Week 24	Phenotypic susceptibility to maraviroc
Correlation of Mutations in gp160 and the V3 Loop and Decreased Susceptibility to Maraviroc	Screening (Day -21 to 0), Day 14, time of virologic failure, Week 24
Change in Lymphocyte Subset CD8 From Day 1	Day 1(Baseline), Day 7, 14, 28 and Weeks 24	Calculated average of CD8 at Day 7, 14, 28 and Week 24 minus CD8 at Day 1
Change in Gene Sequence in Gp-160, and the V3 Loop From Screening Visit (Day -21 to 0) to Day 14, Time of Virologic Failure (See Section 6.5.1) and Week 24	Screening (Day -21 to 0), Day 14, time of virologic failure, and Week 24	Change in gene sequence in gp-160, and the V3 loop from Screening visit (Day -21 to 0) to Day 14, time of virologic failure (See Section 6.5.1) and Week 24