Treatment of Acute HIV Infection With Quad Fixed-dose Combination (FDC) Tablet
Condition: HIV
MeSH terms: HIV Infections
Intervention: (FDC) ELV/COBI/FTC/TDF
Intervention description: Antiretroviral treatment
Intervention MeSH terms: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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