● Extended the double-blind phase from 48 to 96 weeks and added Week 96 evaluations to other secondary objectives, as applicable ● Changed the primary efficacy endpoint of proportion of subjects with HBV DNA levels at Week 48 from below 69 IU/mL to below 29 IU/mL ● Replaced eGFR with serum creatinine as a key secondary safety objective ● Extended duration of ophthalmologic substudy to 144 weeks, with additional ophthalmologic assessment at Weeks 72, 96, and 144 ● Clarified and revised study entry criteria ● Updated statistical section to reflect changes in objectives and to better define analyses of key secondary efficacy and safety endpoints ● Revised the number of subjects for PK substudy from 30 subjects to approximately 16 subjects ● Added section for Management of Potential Posterior Uveitis Cases and section for Multiplicity Adjustments

● Lowered the entry criteria for estimated glomerular filtration rate (eGFR) from ≥ 60 mL/min to ≥ 50 mL/min ● Clarified and revised study entry criteria ● Added clarification regarding subjects who elected an evening study drug dosing schedule: such individuals were no longer required to undergo in-clinic dosing and population PK blood draws at the Week 4 and 12 visits ● Updated statistical analysis methods for key secondary endpoints to align with the TAF HIV Phase 3 development program ● Added cystatin C to the baseline assessments to accommodate the revision to toxicity management for possible nephrotoxicity ● Updated information about the drug formulation for TDF, the comparator, to include the formulation used in developing markets ● Updated information on the management of potential nephrotoxicity ● Added reflex testing for HEV in the event of an ALT elevation

This protocol change was only applicable for China: ● Added the number of subjects to be enrolled in China ● Specified that the dual-energy x-ray absorptiometry (DXA) scan procedure at all protocol-specified visits would be performed only at sites that have the capability ● Added statement that fracture risk assessment at the baseline visit was intended for sites with DXA capability only ● Added hepatitis E virus (HEV) testing as a reflex test for subjects who discontinued study drug and had confirmed ALT elevation ● Updated the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities to reconcile with the scale that was employed in the global program via an administrative letter

● Extended the blinded period of the study to Week 144 (from Week 96). ● Extended the open label period of the study to Week 384 (from Week 144). ● Updated the last study visit date of treatment from Week 144/Early Discontinuation (ED) to Week 384/ED. ● Added 10 study visits (Week 168, 192, 216, 240, 264, 288, 312, 336, 360, and 384/ED) to be conducted during the additional 5 years of the study. ● Revised visit Week numbers to accommodate extension of blinded and open label periods of the study. ● Clarified when open label study drug is to be dispensed to participants who rollover to open-label TAF treatment following Amendment 1 or 2, and under Amendment 3. ● Clarified visit windows for analysis timepoints (Weeks 48, 96, and 144) to be in alignment with DXA windows. ● Added hepatic ultrasound for surveillance of hepatocellular carcinoma every 24 weeks from visit Week 96 to Week 384/ED.