HIV Infections
Conditions
Keywords
HIV, Protease Inhibitor, CCR5 Co-receptor Antagonist, treatment naive
Brief summary
The primary objective of this pilot study is to assess the efficacy of lopinavir/ritonavir (Kaletra, a protease inhibitor, PI) when used in combination with maraviroc (Selzentry, an HIV entry inhibitor) for the treatment of antiretroviral naïve HIV infected patients. Twenty patients will be enrolled and studied for 48 weeks.
Detailed description
As patients with HIV are living longer it is important to explore antiretroviral treatments which may reduce the development of long term complications while preserving future HIV treatment options. This trial explores an antiretroviral treatment regimen which does not include the nucleoside reverse transcriptase inhibitor class which is thought to have long-term toxicity. This is a non-randomized, open label trial in participants meeting entry requirements. Participants will be evaluated at screening, baseline,and weeks 4, 8, 12, 24, 36, and 48 to include clinical assessments as well as laboratory assessments. An interim analysis will be performed when all patients have reached the week 24 visit.
Interventions
Lopinavir/ritonavir 400 mg/100 mg two tablets twice daily with Maraviroc 150 mg one tablet twice daily will be administered for 48 weeks to participants meeting entry criteria.
Sponsors
Abbott
Pfizer
Temple 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
* The patient has signed and dated approved informed consent form. * There is confirmed laboratory diagnosis of HIV infection (positive ELISA HIV antibody test confirmed by Western blot, p24 antigen assay, quantitative HIV-1 RNA assay, or HIV culture). * The patient is at least 18 years of age. * ART-naïve, lopinavir/ritonavir susceptible on genotypic testing, CCR5-tropic virus on Trofile testing (ESTA). * Negative pregnancy test within 72 hours prior to start of study for women of childbearing potential. * Females of childbearing potential and males must utilize effective barrier contraception. * HIV RNA greater than 1,000 copies per mL at entry. * Liver enzymes (AST, ALT) \< 3 times the upper limit of normal.
Exclusion criteria
* Patients who are pregnant or breast-feeding. * Active alcohol or substance abuse sufficient, in the Investigator's opinion that makes compliance to the study protocol unlikely. * Suspected or active HIV-related opportunistic infection or condition requiring acute therapy within 30 days of entry into the trial. * Patients on therapy for hepatitis B. * Patients with hepatitis B surface antigen, or any evidence of active hepatitis B such as positive hepatitis B DNA and/or presence of hepatitis e antigen or e antibody. * Acute hepatitis B or C within 60 days of entry. * Patients harboring preexistent co-receptor CXCR4 tropic or dual-or mixed-tropic HIV. * Patients harboring HIV resistant to lopinavir/ritonavir on genotypic testing. * The presence of decompensated heart failure, myocardial infarction within 1 year, bypass surgery, severe vascular disease, or active hepatobiliary disease. * Concomitant use of rifampin, ergot derivatives (i.e. dihydroergotamine, ergotamine), cisapride, lovastatin, simvastatin, triazolam, orally administered midazolam, carbamazepine, phenytoin, St. John's wort, ketoconazole, itraconazole, clarithromycin, telithromycin, amiodarone, bepridil, flecainide, propafenone, quinidine, voriconazole or nefazodone. * Patients with concomitant diagnosis of malignancy or cancer other than basal cell carcinoma within the past 5 years. * Concomitant use of investigational agents including the use of any investigational vaccines. * Any other clinical conditions or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for study, or unable to comply with the dosing requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assess Proportion of Participants With HIV RNA Levels <50 and < 400 Copies/mL. | week 48 |
Secondary
| Measure | Time frame |
|---|---|
| Assess the Proportion of Participants at Study Termination With VL < 50 Copies/ml. | week 48 |
| Determine the Time to Viral Suppression (VL < 50 Copies/ml). | 48 weeks |
| Number of Participants With HIV RNA < 50 and <400 Copies/ml. | week 24 |
| Assess the Changes in CD4+ T Cell Count. | week 24, 48 |
| Assess Development of HIV Resistance Mutations and in HIV Co-receptor Tropism Changes in Participants Who Develop Virologic Rebound. | week 48 |
| Determine the Median Change in VL From Baseline to Week 24, to Week 48 and to Study Termination. | week 24, week 48 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Single Arm Drug: lopinavir/ritonavir plus maraviroc
lopinavir/ritonavir plus maraviroc: Lopinavir/ritonavir 400 mg/100 mg two tablets twice daily with Maraviroc 150 mg one tablet twice daily will be administered for 48 weeks to participants meeting entry criteria. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Open Label Single Arm |
|---|---|
| Age, Continuous | 29 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Assess Proportion of Participants With HIV RNA Levels <50 and < 400 Copies/mL.
Time frame: week 48
Population: Subject terminated study prior to week 48
Secondary
Assess Development of HIV Resistance Mutations and in HIV Co-receptor Tropism Changes in Participants Who Develop Virologic Rebound.
Time frame: week 48
Population: Subject terminated study prior to week 48
Secondary
Assess the Changes in CD4+ T Cell Count.
Time frame: week 24, 48
Population: Analysis was not performed because only 1 subject was enrolled and terminated study prior to week 48
Secondary
Assess the Proportion of Participants at Study Termination With VL < 50 Copies/ml.
Time frame: week 48
Population: Subject terminated study prior to week 48
Secondary
Determine the Median Change in VL From Baseline to Week 24, to Week 48 and to Study Termination.
Time frame: week 24, week 48
Population: Analysis was not performed as only one subject was enrolled
Secondary
Determine the Time to Viral Suppression (VL < 50 Copies/ml).
Time frame: 48 weeks
Population: Subject terminated study prior to week 48
Secondary
Number of Participants With HIV RNA < 50 and <400 Copies/ml.
Time frame: week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Single Arm | Number of Participants With HIV RNA < 50 and <400 Copies/ml. | 1 Participants |