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

Phase 4TerminatedNCT00855413

University of North Carolina, Chapel Hill15 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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: 1. Women who are pregnant or breast-feeding. 2. Women with a positive pregnancy test on enrollment or prior to study drug administration. 3. Women of reproductive potential who are unwilling or unable to use acceptable methods to avoid pregnancy for the entire study period 4. 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. 5. Known allergy/sensitivity to study drugs or their formulations. 6. Difficulty swallowing capsules/tablets. 7. Inability to communicate effectively with study personnel. 8. Incarceration; prisoner recruitment and participation are not permitted. 9. 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. 10. 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. 11. 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. 12. 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. 13. Known cardiac conduction disease. 14. Prior treatment with any other experimental drug for any indication (within 30 days of initiating study treatment). 15. Unable to discontinue any current medications that are excluded during study treatment. 16. A life expectancy less than twelve months. 17. Acute Viral Hepatitis, including, but not limited to, Hepatitis A, B, or C 18. Chronic Hepatitis B Infection documented by a detectable serum Hepatitis B surface antigen (HBsAg) or plasma HBV DNA

Outcomes

Primary Outcomes

Number of Participants With Virologic Response

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

Time frame: 24 weeks

Secondary Outcomes

Number of Participants With Virologic Response

Virologic response to study treatment defined as plasma HIV RNA measurement \<50 copies/mL at week 48

Time frame: 48 weeks from enrollment

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

Total cumulative levels of HIV RNA detected in the semen of participants from enrollment through week 48.

Time frame: From enrollment through 48 weeks

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

Total number of adverse events observed that were possibly or definitely related to study treatment through week 48

Time frame: Enrollment to week 48

Maximum Etravirine Exposure in Cerebrospinal Fluid Among Participants Who Consented to an Optional Lumbar Puncture