Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

There are now several HIV treatment options for a person with HIV infection who has not yet
been treated. Most people who receive treatment and take their medications as directed have a
good result. This is usually determined by measuring the amount of HIV in the blood (viral
load). The best response is when HIV cannot be found (less than 50 copies/mL) in the blood.
However, it has recently become clear that some people with HIV who are receiving effective
HIV drugs continue to have more health problems than people without HIV infection. Sometimes,
there is damage to organs in the body, including bone, kidneys, and the brain.

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
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.