Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen
Condition: HIV-1 Infection
Intervention: Darunavir; Ritonavir; Tenofovir disoproxil fumarate; Emtricitabine; Placebo for Tenofovir disoproxil fumarate; Placebo for Maraviroc; Maraviroc
Intervention description: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.; Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.; Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.; Emtricitabine was administered orally once a day as one 200 mg capsule.; Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.; Placebo for maraviroc was administered orally once a day as one tablet.; Maraviroc was administered orally once a day as one 150 mg tablet.
Intervention MeSH terms: Ritonavir; Darunavir; Tenofovir; Emtricitabine; Maraviroc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 262.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study was to compare the effects on bones of the following two drug
      combinations:

        -  maraviroc (MVC), emtricitabine (FTC), plus darunavir/ritonavir (DRV/r)

        -  tenofovir (TDF) plus emtricitabine (FTC) plus darunavir/ritonavir (DRV/r)

      Additional study objectives were the following:

        -  To see how the drug combinations affect the brain and kidneys.

        -  To see how well the drug combinations lower the HIV viral load.

        -  To see how safe the drug combinations are, how well people are able to take the study
           drug combinations, and how well their immune systems respond to the study drugs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection

          -  No evidence of exclusionary resistance mutations defined as evidence of any major NRTI
             mutation according to the current IAS list of HIV-1 Resistance Mutations Associated
             with Drug Resistance, or any DRV RAMs (refer to the A5303 PSWP for a list of these
             mutations) on any genotype; or evidence of significant NRTI or DRV resistance on any
             phenotype performed at any time prior to study entry. NNRTI-associated resistance
             mutations were not exclusionary.

          -  ARV drug-naïve, defined as </=10 days of ART at any time prior to study entry, except
             in the instances defined in section 4.1.3 of the protocol.

          -  R5-only tropism based on Trofile testing performed within 90 days prior to study
             entry.

          -  Screening HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry by
             any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA
             certification or its equivalent.

          -  Known hepatitis C virus (HCV) antibody status (performed at any laboratory that had a
             CLIA certification or its equivalent).

          -  Certain laboratory values obtained within 60 days prior to study entry, as defined in
             section 4.1.7 of the protocol.

          -  For women of reproductive potential, negative serum or urine pregnancy test with a
             sensitivity of ≤25 mIU/mL within 72 hours prior to study entry.

          -  Female subjects of reproductive potential, who were participating in sexual activity
             that could lead to pregnancy, must agree to use at least one reliable method of
             contraception (as defined in section 4.1.9.1 of the protocol) while receiving the
             study drugs and for 6 weeks after stopping the medications.

          -  Female subjects who were not of reproductive potential or whose male partner(s) had
             azoospermia were eligible to take study drugs without the use of contraceptives.

          -  Ability and willingness of subject or legal guardian/representative to give written
             informed consent.

          -  Willingness to undergo neuropsychological testing.

          -  DXA scan performed after confirmation of the subject's eligibility by Trofile testing
             but no more than 4 weeks prior to randomization.

        Exclusion Criteria:

          -  Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine,
             systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to
             study entry.

          -  New use of hormonal therapies within 6 months prior to study entry. (Stable therapy
             for ≥6 months was permitted.)

          -  New use of oral contraceptive pills (OCPs) in the past 3 months. (Stable therapy for
             ≥3 months was permitted.)

          -  Any oral, intravenous, or inhaled steroids within 30 days prior to study entry.
             (Intranasal steroids and topical corticosteroids were allowed.)

          -  Known allergy/sensitivity to study drugs or their formulations. (A history of sulfa
             allergy was not an exclusionary condition.)

          -  Known hypersensitivity to soy lecithin.

          -  Serious illness requiring systemic treatment and/or hospitalization until subject
             either completes therapy or was clinically stable on therapy, in the opinion of the
             site investigator, for at least 7 days prior to study entry. (Oral candidiasis,
             vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as
             judged by the site investigator) were not exclusionary conditions.)

          -  Requirement for any current medications that were prohibited with any study drugs.
             (Prohibited medications must be discontinued at least 30 days prior to entry. Refer to
             the A5303 PSWP for a list of prohibited medications.)

          -  The presence of decompensated cirrhosis.

          -  A history of or current, active HBV infection defined as positive hepatitis B surface
             antigen test (or positive HBV DNA in subjects with isolated HBcAb positivity, defined
             as negative HBsAg, negative HBsAb, and positive HBcAb) at screening.

          -  Current or prior use of biphosphonates, teriparatide, raloxifene, or denosumab.

          -  Weight >300 lbs (exceeds weight limit of DXA scanners).

          -  History after 18 years of age of fracture of the spine, hip, wrist, or other site
             thought to be related to osteoporosis or bone fragility.

          -  Currently breastfeeding.

          -  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 drug or alcohol abuse that, in the investigator's opinion, could prevent
             compliance with study procedures or confound the analysis of study endpoints.

          -  Active brain infection (except for HIV-1), fungal meningitis, toxoplasmosis, central
             nervous system (CNS) lymphoma, brain neoplasm, or space-occupying brain lesion
             requiring acute or chronic therapy.