Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

Not Recruiting

Trial ID: NCT01400412


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.

Official Title

A Phase 2b, Double-Blind, Placebo-Controlled, Exploratory Randomized Trial to Determine the Bone, Immunologic, Virologic, and Neurocognitive Effects of a Novel Maraviroc-Containing Antiretroviral Regimen in Treatment-Naïve Patients Infected With R5-Tropic HIV-1

Stanford Investigator(s)

Philip Grant
Philip Grant

Asst Prof-Univ Med Line, Medicine - Infectious Diseases


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    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

   - 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 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.


drug: Tenofovir disoproxil fumarate

drug: Placebo for Tenofovir disoproxil fumarate

drug: Placebo for Maraviroc

drug: emtricitabine

drug: darunavir

drug: ritonavir

drug: Darunavir

drug: Ritonavir

drug: Tenofovir disoproxil fumarate

drug: Emtricitabine

drug: Placebo for Tenofovir disoproxil fumarate

drug: Placebo for Maraviroc

drug: Maraviroc

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Debbie Slamowitz, RN, BSN, ACRN
(650) 723-2804