Efficacy, Safety & Tolerability of Switching EFV/TDF/FTC to BIC/FTC/TAF in Virologically Suppressed Adults With HIV-1

Therapeutic dosage of the tenofovir disoproxil fumarate (TDF) component of ATRIPLA® requires
plasma concentrations of the drug that are associated with nephrotoxicity and decreased bone
mineral density. Tenofovir alafenamide fumarate (TAF) has a unique metabolism that results in
higher intracellular levels of the active phosphorylated moiety tenofovir-diphosphate.
Compared with TDF, the therapeutic dosage of TAF reduces tenofovir plasma concentrations by
over 90%. This reduction in plasma concentration results in decreased renal and bone risks.
TAF has the potential to improve on the efficacy and safety profile of TDF.

Efavirenz, another component of ATRIPLA® is widely associated with neuropsychiatric
side-effects, including sleep disturbances, depression, and anxiety. Switching from Efavirenz
to an integrase inhibitor is associated with improvements in mood.

Bictegravir (BIC) is a novel, once daily integrase inhibitor. It has been shown to have
potent antiviral activity, a favorable pharmacokinetic profile, good tolerability and an
improved resistance profile when compared to previous integrase inhibitors. In a phase 2
trial investigating previously untreated people with HIV, bictegravir plus emtricitabine and
tenofovir alafenamide (BIKTARVY®) vs dolutegravir, plus emtricitabine and tenofovir
alafenamide both showed high efficacy up to 24 weeks and both regimens were well tolerated.

Additionally, switching HAART experienced patients to BIKTARVY® has been shown to be
non-inferior to continuation of regimens containing Atazanavir or Darunavir, when they were
given with either lamivudine/abacavir or FTC/TDF.

The Investigators plan to evaluate in a real world setting the efficacy, safety and
tolerability of switching from the older, established single tablet regimen of ATRIPLA®
(EFV/FTC/TDF) to a new single tablet regimen of BIKTARVY® (BIC/FTC/TAF).

Within the limitations of a real-world study, Investigators have attempted to replicate the
protocol of Gilead Science's Phase 3 study evaluating a switch to BIC/FTC/TAF from
dolutegravir plus either FTC/TAF or FTC/TDF14. This will have the potential benefit of
comparing different regimen switches as well as potentially adding robustness to the body of
data regarding BIC/FTC/TAF.

Inclusion Criteria:

- HIV positive

- On a stable antiretroviral regimen consisting of ATRIPLA® for at least the 6
consecutive months preceding Screening Visit.

- Plasma HIV-1 RNA concentrations at undetectable levels for at least 6 consecutive
months prior to the screening visit and have HIV RNA< 50 copies/mL at the Screening
Visit.

- Estimated GFR ≥30mL/min according to the Cockcroft-Gault formula for creatinine
clearance.

- Hepatic transaminases (AST and ALT) ≤5x upper limit of normal (ULN)

- Total bilirubin ≤1.5 mg/dL, or normal direct bilirubin.

- Adequate hematologic function (hemoglobin ≥ 8.5g/dL; platelets ≥ 50,000/mm3; absolute
neutrophil count ≥1,000/mm3)

- Female subjects of reproductive potential using a reliable and consistent method of
birth control for at least three months prior to study dosing. Male subjects should
use condoms when engaging in intercourse of reproductive potential.

- The ability to understand and sign a written informed consent form, which must be
obtained prior to initiation of study procedures.

Exclusion Criteria:

- A new AIDS-defining condition diagnosed within 30 days prior to screening.

- Individuals with decompensated cirrhosis. (i.e. ascites, encephalopathy, etc.)

- Pregnancy

- A history of malignancy within the past 5 years (prior to screening) or ongoing
malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or
resected, noninvasive cutaneous squamous carcinoma. Individuals with cutaneous KS are
eligible but must not have received any systemic therapy for KS within 30 days prior
to baseline.

- Active, serious infections (other than HIV-1 infection) requiring parenteral
antibiotic or antifungal therapy within 30 days prior to baseline.

- Life expectancy < 1 year.

- Subject participation in any clinical trial without prior approval from the
Investigator.

- Concomitant use of disallowed agents from Table 2

- Participation in any other investigation study 30 days prior to enrollment.