FTC/RPV/TDF on T-Cell Activation, CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir

AIDS Clinical Trials Group (ACTG) A5308 was a single-arm clinical trial to evaluate the
effect of initiating fixed-dose combination (FDC) FTC/RPV/TDF on CD8+ T-cell activation and
other immunologic and virologic biomarkers among treatment-naïve HIV-1 controllers with any
absolute CD4+ T-cell count. At study entry, these participants were followed off ART for a
12-week lead-in period, and then at week 12, participants initiated FDC FTC/RPV/TDF and had
48 weeks of follow-up to evaluate the primary endpoint.

All participants who completed Step 1 (48 weeks of ART) had the option to register to Step 2,
for an additional 48 weeks of follow-up, and had the choice of either continuing FDC
FTC/RPV/TDF or follow-up with no study treatment.

Participants underwent safety and tolerability evaluations throughout the study, including
physical examinations and clinical assessments. Pregnancy tests were performed on women of
childbearing potential. Collection of stored blood plasma/peripheral blood mononuclear cell
(PBMC) samples occurred at entry and weeks 0, 4, 12, 24, 36, 48, 60, 72 and 96 on ART.

Only participants who were on intervention (ART) for at least 24 weeks had samples sent for
testing of immunologic and virologic biomarkers.

Inclusion Criteria:

Step 1

- HIV-1 infection

- ART-naïve defined as ≤7 days of antiretroviral (ARV) treatment at any time prior to
entry

- Documentation of HIV-1 RNA <500 copies/mL verified by at least two measurements prior
to the screening RNA specimen

- Screening HIV-1 RNA <500 copies/mL using an US FDA-approved assay obtained within 60
days prior to study entry by any laboratory that has a CLIA certification or its
equivalent

- Laboratory values obtained within 60 days prior to entry by any laboratory that has a
CLIA certification or its equivalent:

- Absolute neutrophil count (ANC) >=500/mm^3

- Hemoglobin >=8.0 g/dL

- Platelet count >=40,000/mm^3

- Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT),
and alkaline phosphatase <=5 X Upper Limit of Normal (ULN)

- Total bilirubin <=2.5 X ULN

- Calculated creatinine clearance (CrCl) >=60 mL/min

- For females of reproductive potential, negative serum or urine pregnancy test within
48 hours prior to study entry by any clinic or laboratory that has a CLIA
certification or its equivalent

- Female subjects of reproductive potential, who are participating in sexual activity
that could lead to pregnancy, must agree to use at least one reliable form of
contraceptive (ie, condoms (male or female) with or without a spermicidal agent; a
diaphragm or cervical cap with spermicide; an intrauterine device (IUD); or
hormone-based contraceptive) while receiving the protocol-specified treatment and for
6 weeks after stopping the medications

- No evidence of any exclusionary resistance mutations based on results from any
genotype assay from any laboratory that has a Clinical Laboratory Improvement
Amendments (CLIA) certification or its equivalent

Step 2

- Completion of Step 1

- Ability and willingness of subject to choose to receive either open-label ART FDC
(FTC/RPV/TDF) or no study treatment for an additional 48 weeks

- For females of reproductive potential, negative serum or urine pregnancy test within
48 hours prior to the week 60 visit by any clinic or laboratory that has a CLIA
certification or its equivalent

Exclusion Criteria:

Step 1

- Chronic hepatitis B virus (HBV) infection (documented by hepatitis B surface antigen
(HBsAg) seropositivity)

- Breastfeeding

- Use of immunomodulators (eg, interleukins, interferons, cyclosporine), topical
imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy
within 30 days prior to study entry or plans to start immunomodulators, topical
imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy
during the study

- Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or
their formulation

- Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements

- Acute or serious illness requiring systemic treatment and/or hospitalization within 30
days prior to entry

- Symptomatic HIV disease and/or AIDS-defining illness.

- Vaccinations within 7 days prior to study entry

- Plans to initiate hepatitis C treatment during the study

- Perinatally-acquired HIV

- Use of any of the following medications within 7 days prior to study entry:

- St. John's wort (Hypercium perforatum)

- Anticonvulsants (eg, oxacarbazepine, phenobarbital, phenytoin)

- Anti-infectives (eg, rifabutin, rifampin, rifapentine)

- Corticosteroids (eg, dexamethasone (more than 1 dose))

- Proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole,
rabeprazole)

Step 2

- Plans to start immunomodulators, topical imiquimod, HIV vaccine, systemic cytotoxic
chemotherapy, or investigational therapy during Step 2 of the study

- Plans to initiate hepatitis C treatment during Step 2 of the study

NOTE: Please refer to the protocol for detailed eligibility criteria.