HIV-1 Infection, HIV Infections
Conditions
Keywords
Treatment naive
Brief summary
The objective of this study is to evaluate the safety and efficacy of a novel combination antiretroviral therapy regimen consisting of maraviroc plus darunavir/ritonavir in treatment-naive patients infected with R5-tropic HIV-1. The hypothesis is that in treatment-naive subjects infected with R5-tropic HIV-1, combination antiretroviral therapy with maraviroc plus darunavir/ritonavir is well tolerated and efficacious.
Interventions
DRUGmaraviroc
150 mg tab by mouth once daily for 96 weeks
DRUGdarunavir
800 mg tab by mouth once daily for 96 weeks
DRUGritonavir
100 mg capsule by mouth once daily for 96 weeks
Sponsors
Pfizer
Tibotec, Inc
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection, as documented by any licensed HIV test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA any time prior to study entry * Plasma HIV-1 RNA 5, 000 to 500,000 copies/mL obtained within 90 days prior to study entry * Exclusive R5 tropism based on enhanced sensitivity Trofile assay done within 90 days prior to entry * CD4 cell count \> 100 cells/mm3 within 90 days prior to study entry * HIV genotype (for RT and protease) performed at any time before study entry (Subjects with single or combination NNRTI or NRTI RAM(s) at screening are permitted) * ARV drug-naïve, defined as no previous ARV treatment at any time prior to study entry * Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry * Negative result from a hepatitis C antibody test performed within 90 days prior to study entry * Laboratory values obtained within 30 days prior to study entry: * ANC \>=750/mm3 * Hemoglobin \>=10 g/dL * Platelets \>=50,000/mm3 * AST (SGOT), ALT (SGPT), and alkaline phosphatase \<=5 x ULN * Calculated creatinine clearance (CrCl) \>=30 mL/min, as estimated by the Cockcroft-Gault equation\* * Negative serum or urine pregnancy test within 48 hours prior to study entry for women with reproductive potential * If participating in sexual activity that could lead to pregnancy, the study subjects with reproductive potential must use one form of contraceptive while receiving protocol-specified medications and for 60 days after stopping the medications. * Men and women age \>=18 years * Ability and willingness of subject or legal guardian/representative to provide informed consent
Exclusion criteria
* Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry * Screening HIV genotype obtained any time prior to study entry with any DRV RAM (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V) * Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy. NOTE: Subjects receiving stable physiologic glucocorticoid doses (defined as prednisone ≤10 mg/day \[or equivalent\] as a stable or tapering dose) are permitted. Subjects receiving corticosteroids for acute therapy for PCP or asthma exacerbation, or receiving a short course (defined as ≤2 weeks of pharmacologic glucocorticoid therapy) are permitted * Breast-feeding * Requirement for any medication that is prohibited with a study medication * Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion * Active drug or alcohol use or dependence that could interfere with adherence to study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 RNA >50 | 24 weeks | Percentage of participants with confirmed plasma HIV-1 RNA \> 50 copies/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL | 48 weeks | Percentage of participants with confirmed plasma HIV-1 RNA level \>50 copies/mL |
| Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher | 96 weeks | Signs/symptoms or laboratory toxicities of Grade 3 or higher, or of any grade which led to a permanent change or discontinuation of study treatment regimen |
| Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES | At study entry and at the time of virologic failure | — |
| Percentage of Participants With Virologic Failure or Off Study Treatment Regimen | 24 weeks | Percentage of participants with virologic failure (confirmed plasma HIV-1 RNA \> 50 copies/mL) or off study treatment regimen (composite end point) |
| Trough Concentrations (Ctrough) of Maraviroc | 24 hours | Average trough concentration (Ctrough) of maraviroc |
| Median CD4 Count Change From Baseline | 96 weeks | Median changes from baseline in peripheral CD4+ T-cell count |
| Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL | 96 weeks | Proportion of participants with confirmed plasma HIV-1 RNA level \>50 copies/mL |
| Drug Adherence, Number of Participants With Missed Doses | Week 24 | Drug adherence, assessed as number of participants with missed doses over four-day recall |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc + Darunavir/Ritonavir maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | never initiated treatment | 1 |
Baseline characteristics
| Characteristic | Maraviroc + Darunavir/Ritonavir |
|---|---|
| Age, Continuous | 38 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Median HIV-1 RNA | 4.62 log 10 copies |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Percentage of Participants With Plasma HIV-1 RNA >50
Percentage of participants with confirmed plasma HIV-1 RNA \> 50 copies/mL
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Percentage of Participants With Plasma HIV-1 RNA >50 | 12.5 percentage of participants |
Secondary
Drug Adherence, Number of Participants With Missed Doses
Drug adherence, assessed as number of participants with missed doses over four-day recall
Time frame: Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Drug Adherence, Number of Participants With Missed Doses | 0 participants |
Secondary
Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES
Time frame: At study entry and at the time of virologic failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES | 0 participants |
Secondary
Median CD4 Count Change From Baseline
Median changes from baseline in peripheral CD4+ T-cell count
Time frame: 96 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Median CD4 Count Change From Baseline | 247 cells per mm^3 |
Secondary
Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL
Percentage of participants with confirmed plasma HIV-1 RNA level \>50 copies/mL
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL | 8.3 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure or Off Study Treatment Regimen
Percentage of participants with virologic failure (confirmed plasma HIV-1 RNA \> 50 copies/mL) or off study treatment regimen (composite end point)
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Percentage of Participants With Virologic Failure or Off Study Treatment Regimen | 12.5 percentage of participants |
Secondary
Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL
Proportion of participants with confirmed plasma HIV-1 RNA level \>50 copies/mL
Time frame: 96 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL | 10 percentage of participants |
Secondary
Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher
Signs/symptoms or laboratory toxicities of Grade 3 or higher, or of any grade which led to a permanent change or discontinuation of study treatment regimen
Time frame: 96 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher | 1 participants |
Secondary
Trough Concentrations (Ctrough) of Maraviroc
Average trough concentration (Ctrough) of maraviroc
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc + Darunavir/Ritonavir | Trough Concentrations (Ctrough) of Maraviroc | 39.3 ng/mL | Standard Deviation 22.8 |