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

NCT00855413 | Terminated Phase 4 Results DMC

• 1 other identifier: CID 0821
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Acute HIV Infection; HIV Infections

Keywords

Acute HIV; HIV; Treatment Naive; Acute Infections

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Virologic Response

  Virologic response defined as plasma HIV RNA measurement \<200 copies/mL at week 24

  24 weeks

Secondary Outcomes (37)

• Number of Participants With Virologic Response

  48 weeks from enrollment

• Median Change in CD4 Cell Count From Week 0 to Week 24.

  week 0, week 24

• Median Change in CD4 Cell Count From Week 0 to Week 48.

  48 weeks from enrollment

• HIV RNA Levels Immediately Prior to Initiating Study Treatment.

  HIV RNA level at enrollment

• Median Time to HIV RNA Suppression to <200 Copies/mL

  From enrollment to the date of HIV RNA suppression, assessed up to Week 48

Study Arms (1)

Darunavir/Ritonavir and Etravirine

OTHER

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; Drug: Ritonavir; Drug: Etravirine

Interventions

Darunavir DRUG

800 mg orally once daily

Also known as: Prezista

Darunavir/Ritonavir and Etravirine

Ritonavir DRUG

100 mg orally once daily

Also known as: Norvir

Darunavir/Ritonavir and Etravirine

Etravirine DRUG

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

Also known as: Intelence

Darunavir/Ritonavir and Etravirine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documentation of Acute HIV Infection as defined above.
• Men and women age ≥18 years.
• 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.
• Screening HIV-1 RNA \>1,000 copies/mL obtained within 30 days at study entry.
• Lab values obtained within 30 days prior to study entry:
• Absolute neutrophil count \>500/mm3
• Hemoglobin \> 8.5 g/dL for men and \> 8.0 g/dL for women
• Platelet count \>50,000/mm3
• AST (SGOT) ≤2.5 x ULN
• ALT (SGPT) ≤2.5 x ULN
• Total bilirubin \<2.5 x ULN
• 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)
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (2)

The University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27707, United States

Location

Related Publications (3)

• Gay CL, Mayo AJ, Mfalila CK, Chu H, Barry AC, Kuruc JD, McGee KS, Kerkau M, Sebastian J, Fiscus SA, Margolis DM, Hicks CB, Ferrari G, Eron JJ; Duke-UNC Acute HIV Infection Consortium. Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection. AIDS. 2011 Apr 24;25(7):941-9. doi: 10.1097/QAD.0b013e3283463c07.

  PMID: 21487250 BACKGROUND

• C Gay, O Dibben, A Stacey, N Gasper-Smith, M Liu, N Goonetilleke, G Ferrari, J Eron, C Hicks, A McMichael, B Haynes, P Borrow, M Cohen, the Duke-UNC CHAVI 001 Clinical Working Group. "Effect(s) of antiretroviral treatment on acute HIV infection." XVII International AIDS Conference, 2008 Abstract no. THPE0086.

  BACKGROUND

• Gay CL, Neo DT, Devanathan AS, Kuruc JD, McGee KS, Schmitz JL, Sebastian J, Shaheen NJ, Ferrari G, McKellar M, Fiscus SA, Hicks CB, Robertson K, Kashuba ADM, Eron JJ, Margolis DM. Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection. AIDS. 2020 Nov 1;34(13):1923-1931. doi: 10.1097/QAD.0000000000002652.

  PMID: 32773474 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Darunavir; Ritonavir; etravirine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Limitations and Caveats

Early termination prior to target enrollment due to slow enrollment limited analysis involving optional procedures. Lack of paired (baseline and followup) samples from optional procedures also limited ability to perform these analyses.

Results Point of Contact

• Title: Dr. Cynthia Gay
• Organization: The University of North Carolina

cynthia_gay@med.unc.edu

9198432726

Study Officials

• Cynthia Gay, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• David M Margolis, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: March 2, 2009
• First Posted: March 4, 2009
• Study Start: March 1, 2009
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: October 17, 2017
• Results First Posted: October 17, 2017

Record last verified: 2017-09

Locations

US (2)