Clinical Trials

MainTitle

HIV Viremia and Persistence in Acutely HIV-Infected Patients Treated With Darunavir/Ritonavir and Etravirine

This study has been terminated
( Study halted by sponsor due to slow enrollment. )

Sponsor
University of North Carolina, Chapel Hill

Collaborator
Janssen Pharmaceuticals

Information provided by (Responsible Party)
Cynthia L Gay, MD, University of North Carolina, Chapel Hill

ClinicalTrials.gov Identifier
NCT00855413

First received: March 2, 2009
Last updated: September 12, 2017
Last Verified: September 2017
History of Changes
Purpose

Purpose

Purpose: This is a pilot study to evaluate HIV viremia and persistence in acutely HIV infected antiretroviral naïve patients treated with Darunavir/ritonavir and Etravirine

Participants: 20 participants, age 18 and older, HIV infected, antiretroviral naïve patients

Procedures (methods): ARV treatment with Darunavir/ritonavir and Etravirine,

Optional studies:

Genital secretion samples, Cerebrospinal fluid samples, Leukapheresis, Endoscopy/colonoscopy

Condition Intervention Phase
Acute HIV Infection
HIV Infections

Drug : Darunavir
Drug : Ritonavir
Drug : Etravirine
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CID 0821 - Pilot Study to Evaluate HIV Viremia and Persistence in Acutely HIV-Infected Antiretroviral Naïve Patients Treated With Darunavir/Ritonavir and Etravirine

Further study details as provided by Cynthia L Gay, MD, University of North Carolina, Chapel Hill:

Primary Outcome Measures

  • Number of Participants With Virologic Response [ Time Frame: 24 weeks ]
    Virologic response defined as plasma HIV RNA measurement <200 copies/mL at week 24
Secondary Outcome Measures:
  • Number of Participants With Virologic Response [ Time Frame: 48 weeks from enrollment ]
    Virologic response to study treatment defined as plasma HIV RNA measurement <50 copies/mL at week 48
  • Median Change in CD4 Cell Count From Week 0 to Week 24. [ Time Frame: week 0, week 24 ]
  • Median Change in CD4 Cell Count From Week 0 to Week 48. [ Time Frame: 48 weeks from enrollment ]
  • HIV RNA Levels Immediately Prior to Initiating Study Treatment. [ Time Frame: HIV RNA level at enrollment ]
  • Median Time to HIV RNA Suppression to <200 Copies/mL [ Time Frame: From enrollment to the date of HIV RNA suppression, assessed up to Week 48 ]
  • HIV RNA Detection in Semen [ Time Frame: From enrollment through 48 weeks ]
    Total cumulative levels of HIV RNA detected in the semen of participants from enrollment through week 48.
  • Number of Participants Who Stopped Study Treatment Due to Adverse Event or Intolerance [ Time Frame: Enrollment to Week 48 ]
  • Adverse Events Possibly or Definitely Related to Study Treatment Through Week 48 [ Time Frame: Enrollment to week 48 ]
    Total number of adverse events observed that were possibly or definitely related to study treatment through week 48
  • Maximum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture [ Time Frame: Week 4 and week 48 ]
  • Minimum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture [ Time Frame: Week 4 and week 48 ]
  • Maximum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture [ Time Frame: Week 4 and week 48 ]
  • Minimum Darunavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture [ Time Frame: Week 4 and week 48 ]
  • Maximum Ritonavir Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture [ Time Frame: Week 4 and Week 48 ]
  • Minimum Ritonavir Exposure Range in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture [ Time Frame: Week 4 and week 48 ]
  • Maximum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen [ Time Frame: Weeks 0-4 and weeks 12, 48 ]
  • Minimum Etravirine Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen [ Time Frame: Weeks 0-4 and weeks 12, 48 ]
  • Maximum Darunavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen [ Time Frame: Weeks 0-4 and weeks 12, 48 ]
  • Minimum Darunavir Exposure Range in Semen Among Participants Who Consented to an Optional Collection of Semen [ Time Frame: Weeks 0-4 and weeks 12, 48 ]
  • Maximum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen [ Time Frame: Weeks 0-4 and Weeks 12, 48 ]
  • Minimum Ritonavir Exposure in Semen Among Participants Who Consented to an Optional Collection of Semen [ Time Frame: Weeks 0-4 and Weeks 12, 48 ]
  • Maximum Etravirine Exposure in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure [ Time Frame: between Week 4-12 and between Weeks 36-48 ]
  • Minimum Etravirine Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure [ Time Frame: between Week 4-12 and between Weeks 36-48 ]
  • Maximum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure [ Time Frame: between Week 4-12 and between Weeks 36-48 ]
  • Minimum Darunavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure [ Time Frame: between week 4-12 and between weeks 36-48 ]
  • Maximum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure [ Time Frame: between week 4-12 and between Weeks 36-48 ]
  • Minimum Ritonavir Exposure Range in Ileal Tissue Among Participants Who Consented to an Optional Gut Biopsy Procedure [ Time Frame: between week 4-12 and between weeks 36-48 ]
  • Number of Participants With HIV RNA Measurement Above the Limits of Detection in Cerebrospinal Fluid [ Time Frame: Week 4 and Week 48 ]
  • Number of Participants With Neurocognitive Impairment at Baseline [ Time Frame: Week 2 or 4 ]
  • Number of Participants With Neurocognitive Impairment at Week 24 [ Time Frame: Week 24 ]
  • Number of Participants With Neurocognitive Impairment at Week 48 [ Time Frame: Week 48 ]
  • Overall Neurocognitive Impairment Score at Week 2 or 4 [ Time Frame: Week 2 or 4 ]
    Neuropsychological performance was assessed at Week 2 or 4, Week 24 and Week 48 in the following measures: Premorbid/language (Wide Range Achievement Test 4 -Reading Subtest), Learning (HVLT-R, Hopkins Verbal Learning Test-Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score was created by averaging all tests. Participants also completed the self-reported functional status Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
  • Overall Neurocognitive Impairment at Week 24 [ Time Frame: Week 24 ]
    Neuropsychological performance was assessed at week 2 or 4, week 24 and week 48 in the following measures: Premorbid/language (Wide Range Achievement Test 4 -Reading Subtest), Learning (Hopkins Verbal Learning Test - Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score of neurocognitive functioning was created by averaging all tests. Participants also completed Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
  • Overall Neurocognitive Impairment at Week 48 [ Time Frame: Week 48 ]
    Neuropsychological performance was assessed at baseline (week 2 or 4), week 24 and week 48 in the following domain (measures): Premorbid/language (Wide Range Achievement Test (WRAT) 4 - Reading Subtest), Learning (HVLT-R, Hopkins Verbal Learning Test - Revised), Memory (HVLT-R), Speed of Processing (Trailmaking A (Army Individual Test Battery, 1944), 1974, Stroop color, Attention (WAIS-III Symbol Search; Stroop word, Fine motor, Executive (Trailmaking B, Stroop interference, Letter, Category Fluency. An overall summary score of neurocognitive functioning was created by averaging all tests. Participants also completed the self-reported functional status Patient's Assessment of Own Functioning Inventory (PAOFI) and the Activities of Daily Living Scale (ADLS). Best available demographically corrected normative data were utilized to create z scores. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
  • Change in Overall Neurocognitive Impairment From Baseline to Week 24 or 48 [ Time Frame: Baseline to Week 24 or 48 ]
    Change in overall z score from baseline to week 24 or 48. A negative z score denotes below-average performance relative to a US normative comparison population. A higher z score is a better outcome.
  • Correlation of HIV RNA Levels in CSF and Drug Levels With Neurocognitive Functioning [ Time Frame: From enrollment through Week 48 ]
  • Correlation of Time to HIV RNA Levels <200 Copies/mL With Improvement in Neurocognitive Functioning From Baseline to Week 24 and 48 [ Time Frame: Baseline to Week 24 and 48 ]
  • HIV RNA Detection in Ileal Biopsy Specimens [ Time Frame: Weeks 4 and 48 ]
    Average HIV RNA detected in the ileal biopsy specimens per participant over weeks 4 and 48.

Enrollment: 15
Study Start Date: March 2009
Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: Darunavir/Ritonavir and Etravirine
Darunavir/Ritonavir 800 mg/100 mg orally once daily. ETR will be given 200 mg orally twice daily, although patients may choose to take ETR 400 mg QD to have a simpler all QD regimen.
Drug: Darunavir

800 mg orally once daily

Other Name: Prezista
Drug: Ritonavir

100 mg orally once daily

Other Name: Norvir
Drug: Etravirine

200 mg orally twice daily, although patients may choose to take ETR 400 mg QD to have a simpler all QD regimen

Other Name: Intelence

Detailed Description:

Study Design
This is a multicenter, single arm, 48-week open-label pilot study of DRV/R & ETR in acute HIV infection. Study sites will be members of the Duke-UNC Acute HIV Infection Study Consortium. If baseline resistance is detected after treatment begins (e.g. evidence of pre-existing baseline resistance (genotypic or phenotypic) that may adversely affect the efficacy of the study regimen), the patient may elect to alter treatment as per best clinical practice. The new regimen will not be provided by the study, but will be obtained for the participant through available clinical resources.
After patients are identified with acute HIV infection, they will be offered the opportunity to participate in the study. Patients will also be offered the opportunity to co-enroll in CHAVI 001 and 012, studies that follow the virological and immunological response of patients with AHI, regardless of the initiation of ART. An overall consent form will be signed for study participation, and separate informed consents with signatures will be obtained for optional studies. Patients will be eligible for participation after signing the overall consent - agreeing to participate in studies of other compartment specimens is not required for enrollment. At the initial visit, patient eligibility will be confirmed with appropriate laboratory testing (see "STUDY POPULATION"). When eligibility is verified, entry laboratory studies will be obtained, and the participants will be started on DRV/r, and ETR. All participants will be followed at regular intervals thereafter as specified in the schedule of evaluations. Participants meeting criteria for virologic failure will be offered the opportunity to switch to the best available regimen as selected by their HIV provider.
Hypothesis
Combination therapy with DRV/R & ETR will suppress plasma viremia and improve immunologic function in antiretroviral (ART)-naïve, acutely HIV-infected (AHI) patients, and will limit replication in HIV-1 cellular compartments.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  1. Documentation of Acute HIV Infection as defined above.
  2. Men and women age ≥18 years.
  3. Participants will be ART naïve, defined as ≤14 days of antiretroviral treatment at any time prior to entry. The only exceptions are: Post-exposure prophylaxis (PEP) provided the patient was documented as HIV-1 negative at least 3-6 months after completion of the PEP treatment.
  4. Screening HIV-1 RNA >1,000 copies/mL obtained within 30 days at study entry.
  5. Lab values obtained within 30 days prior to study entry:
  6. Absolute neutrophil count >500/mm3
  7. Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women
  8. Platelet count >50,000/mm3
  9. AST (SGOT) ≤2.5 x ULN
  10. ALT (SGPT) ≤2.5 x ULN
  11. Total bilirubin <2.5 x ULN
  12. Calculated creatinine clearance (Cockcroft-Gault formula) > 30mL/min:
    • CrCl = (140-age) x body weight (kg) (x 0.85 if female)
    • Serum creatinine [mg/dL] x (72)
  13. For women of reproductive potential, a negative serum or urine pregnancy test within 7 days prior to initiating antiretroviral study medications. Reproductive potential is defined as females who have reached menarche and have not been post-menopausal for at least 24 consecutive months, or have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, or salpingotomy). Acceptable documentation of surgical sterilization includes patient-reported history.
  14. If participating in sexual activity that could lead to pregnancy, female study patients must use at least one form of contraception, which could consist only of a barrier method. All patients must continue to use contraception for 6 weeks after stopping the study medications. Acceptable methods of contraception include: condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, or IUD. Female volunteers not of reproductive potential are not required to use contraception.
  15. Ability and willingness of patient to give written informed consent.

  • Exclusion Criteria:
  • Women who are pregnant or breast-feeding.
  • Women with a positive pregnancy test on enrollment or prior to study drug administration.
  • Women of reproductive potential who are unwilling or unable to use acceptable methods to avoid pregnancy for the entire study period
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
    • Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is permitted.
  • Known allergy/sensitivity to study drugs or their formulations.
  • Difficulty swallowing capsules/tablets.
  • Inability to communicate effectively with study personnel.
  • Incarceration; prisoner recruitment and participation are not permitted.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or confound the analysis of study endpoints.
  • Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neurological examination or neuropsychological test results.
  • Active brain infection (except for HIV-1), brain neoplasm, space-occupying brain lesion requiring acute or chronic therapy. Participants with any fungal meningitis, parasitic infection, or CNS lymphoma are excluded from participation.
  • Serious illness requiring systemic treatment and/or hospitalization until patient 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. NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction.
  • Known cardiac conduction disease.
  • Prior treatment with any other experimental drug for any indication (within 30 days of initiating study treatment).
  • Unable to discontinue any current medications that are excluded during study treatment.
  • A life expectancy less than twelve months.
  • Acute Viral Hepatitis, including, but not limited to, Hepatitis A, B, or C
  • Chronic Hepatitis B Infection documented by a detectable serum Hepatitis B surface antigen (HBsAg) or plasma HBV DNA

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT00855413

    Locations

    United States, North Carolina
    The University of North Carolina - Chapel Hill
    Chapel Hill, North Carolina, United States, 27599
    Duke University
    Durham, North Carolina, United States, 27707

    Sponsors and Collaborators

    University of North Carolina, Chapel Hill
    Janssen Pharmaceuticals

    Investigators

    Principal Investigator: Cynthia Gay, MD, MPH University of North Carolina, Chapel Hill
    Principal Investigator: David M Margolis, MD University of North Carolina, Chapel Hill
    More Information

    More Information


    Responsible Party: Cynthia L Gay, MD, Clinical Assistant Professor, University of North Carolina, Chapel Hill  
    ClinicalTrials.gov Identifier: NCT00855413   History of Changes  
    Other Study ID Numbers: CID 0821  
    Study First Received: March 2, 2009  
    Last Updated: September 12, 2017  

    Keywords provided by Cynthia L Gay, MD, University of North Carolina, Chapel Hill:

    Acute HIV
    HIV
    Treatment Naive
    Acute Infections

    Additional relevant MeSH terms:
    Infection
    Communicable Diseases
    HIV Infections
    Acquired Immunodeficiency Syndrome
    Viremia
    Ritonavir
    Darunavir
    Etravirine

    ClinicalTrials.gov processed this data on December 18, 2017
    This information is provided by ClinicalTrials.gov.