Treatment of Acute HIV Infection With Quad Fixed-dose Combination (FDC) Tablet (PHI04)

Treatment of Acute HIV Infection With the Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate, A Pilot Study of Response to Therapy and HIV Pathogenesis

This is a multicenter, single arm, 48-week open-label study of FDC ELV/COBI/FTC/TDF [Stribild] in acute HIV infection. Study sites will be members of the Duke-UNC Acute HIV Infection Study Consortium. Participants will be enrolled for 96 weeks. Clinical care and study drug (ELV/COBI/FTC/TDF) will be provided for the first 48 weeks. After week 48, clinical care but not study drug will be provided through week 96. A study participant suppressed at week 48 can continue on FDC ELV/COBI/FTC/TDF.

The primary hypothesis is that once daily fixed-dose combination elvitegravir (ELV), cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) will rapidly reduce viral replication to <50 copies RNA/ml in participants with acute HIV infection. The secondary hypotheses to be considered are 1) virologic response rates as measured by plasma HIV RNA levels will be non-inferior or superior to a historical group of participants from the PHI cohort treated with EFV/FTC/TDF, 2) compared to historical controls treated with EFV/FTC/TDF, plasma HIV RNA will decrease more rapidly in PHI participants treated with ELV/COBI/FTC/TDF, 3) compared to historical controls treated with EFV/FTC/TDF, immune activation as measured by the proportion CD4+ and CD8+ cells expressing HLA-DR and CD38+ will decrease more rapidly in PHI participants treated with ELV/COBI/FTC/TDF, 4)in a subset of participants samples will be obtained from compartments such as the gastrointestinal tract, and lymphoid tissues to assess changes over time in parameters such as HIV-1 RNA, immunologic responses to HIV, and tissue and anatomic reservoirs. We hypothesize that treatment with the ELV/COBI/FTC/TDF will demonstrate improved viral clearance in these compartments as compared to historical controls treated with EFV/FTC/TDF. 5) in a subset of participants who remain suppressed on therapy, resting CD4 cells with replication-competent HIV-1 (latent reservoir) will be quantitated and compared to similar measurements in PHI participants treated with EFV/FTC/TDF. In addition, we will compare these results to those measured in HIV-1 infected participants treated and 6) ELV/COBI/FTC/TDF will be well tolerated, and the proportion of participants who require treatment modification will be less than that observed in participants treated with EFV/FTC/TDF.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: (FDC) ELV/COBI/FTC/TDF

Detailed Description

None desired

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC at Chapel Hill
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Acute HIV infection is defined as:

1. A positive 4th generation HIV Ag/Ab Combination Assay and HIV RNA (NAAT or viral load) and one of the following within 30 days of study entry:

   • a negative HIV rapid test
   • negative/indeterminate Western Blot

   OR

2. A negative or indeterminate HIV antibody, antigen, or nucleic acid amplification test (NAAT) and any one of the following within 30 days of study entry:

   • A detectable HIV nucleic acid in blood confirmed by a second NAAT
   • Positive p24 antigen
   • A positive HIV antibody test according to standard criteria obtained within 45 days after an initial negative or indeterminate HIV antibody, antigen, or nucleic acid amplification.

Inclusion Criteria:

1. Acute HIV Infection (as defined above) within 30 days of study entry.
2. Age >18 years.
3. ART-naive (<14 days of previous antiretroviral treatment. Exceptions are: Post-exposure prophylaxis (PEP) if participant was documented as HIV-negative at least 3 months after completion of PEP.

4. Lab values within 30 days prior to study entry:

   1. Absolute neutrophil count >500/mm3
   2. Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women
   3. Platelet count >50,000/mm3
   4. AST (SGOT)> .2.5 x ULN
   5. ALT (SGPT)> .2.5 x ULN
   6. Total bilirubin <2.5 x ULN
   7. Calculated creatinine clearance (Cockcroft-Gault formula) > 70mL/min:
5. For women of reproductive potential, a negative pregnancy test within 72 hours 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.
6. Female study participants must use a reliable form of barrier contraception, such as a condom, even if they also use other methods of birth control. All participants must continue to use contraception for 12 weeks after stopping study medications. Acceptable methods of barrier contraception include: condoms (male or female), diaphragm, or cervical cap. These can be used alone or in tandem with hormonal or IUD method.
7. Ability and willingness of participant to give written informed consent.

Exclusion Criteria:

1. Women who are pregnant or breast-feeding.
2. Women with a positive pregnancy test prior to study drug administration.
3. Men who have sex with women, and women of reproductive potential unwilling or unable to use an acceptable, reliable barrier method of contraception for the entire study period and 12 weeks afterwards.
4. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days of study entry (Prednisone 10 mg QD or less is permitted.
5. Known allergy/sensitivity to study drugs
6. Difficulty swallowing pills
7. Inability to communicate effectively with study personnel
8. Incarceration; prisoner recruitment and participation are not permitted
9. Active drug or alcohol use that, in the opinion of the site investigator, would interfere with participation in the study
10. Any active psychiatric illness 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
12. Serious illness requiring systemic treatment and/or hospitalization until patient either completes therapy or is clinically stable on therapy for at least 7 days prior to study entry
13. Known cardiac conduction disease
14. Prior treatment with any other experimental drug within 30 days of initiating study treatment
15. Unable to discontinue any current medications that are excluded during study treatment
16. 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
19. Calculated creatinine clearance (Cockcroft-Gault formula) <70mL/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quad FDC; FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks	Drug: (FDC) ELV/COBI/FTC/TDF; Antiretroviral treatment; Other Names: STRIBILD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With a Viral Load Measurement of <200 Copies/mL at Week 24	24 weeks
Virologic Efficacy of the Fixed Dose Combination (FDC) ELV/COBI/FTC/TDF Given Once Daily to Participants With Acute HIV Infection as Determined by the Proportion of Treated Participants With HIV-1 RNA to <50 Copies/mL at Week 48	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Immune Activation as Measured by the Proportion of CD4+ and CD8+ Cells Expressing HLA-DR and CD38+	48 weeks
Rate of Virologic Decline in the First 48 Weeks of Treatment Comparing FDC ELV/COBI/FTC/TDF to FDC EFV/FTC/TDF	48 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Grade 3 or Grade 4 Adverse Events	48 weeks
Number of Participants With Adverse Events Related to Study Drug	48 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Mehri McKellar, MD, Duke University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: September 21, 2012
• First Submitted That Met QC Criteria: September 25, 2012
• First Posted (Estimate): September 27, 2012

Study Record Updates

• Last Update Posted (Actual): April 12, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: Pro00035447; IN-US-236-0124 (Other Grant/Funding Number: Funder)