Study will evaluate the safety and tolerability of once daily Biktarvy for 28 days for prevention of HIV infection in HIV-1-seronegative adults after high-risk sexual contact. (non-occupational post exposure prophylaxis - nPEP)

Non-randomized, open label single arm trial conducted at Fenway Health as a single site. 100 subjects will be enrolled following a high risk sexual exposure in which HIV exposure is a concern. Each person will be provided with detailed informed consent and if they agree, will receive a 28 day regimen of BIC/F/TAF (Biktary) in a single fixed-dose tablet. Subjects will be seen for 3 visits over a period of four months in which assessments will be done to evaluate safety of product, tolerability of product and HIV status. All subjects will be compared to historical controls in the previous one daily TDF-based nPEP studies which were conducted at Fenway Health.

Inclusion Criteria:

1. > Age of 18 at time of first visit.

2. HIV uninfected

3. Willing and able to provide written informed consent.

4. Willing and able to provide adequate locator information.

5. Willing and able to return to all study visits.

6. Willing to participate in all study procedures.

7. Childbearing age: Willing to use contraception for as long as they are on study medication plus 7 days after. (Appendix A: list of approved contraception).

8. Possible sexual exposure to HIV-1, recent enough to permit receiving the first dose of study medication within 72 hours from the end of the exposure. A possible exposure could include:

   1. Condomless anal, vaginal, oral, or mucosal (e.g. conjunctival) exposure to ejaculate from a partner who is HIV-1 infected or high risk for HIV infection and of unknown HIV-1 serostatus (may include protected sexual exposure with condom failure, breakage or slippage); or
   2. Condomless penile exposure to cervicovaginal secretions or anorectal secretions from a partner who is HIV-1 infected or high risk for HIV infection and of unknown HIV-1 serostatus (may include protected sexual exposure with condom failure, breakage or slippage)

Exclusion Criteria:

1. An active psychiatric illness or active drug or alcohol abuse that, in the opinion of the investigator, could prevent compliance with study procedures.
2. Pregnancy and/or breastfeeding.
3. People who are actively trying to become pregnant.
4. Acute or chronic hepatitis B infection.
5. Acute or chronic renal disease.
6. Creatinine clearance at or below 30 mL/min (Cockcroft-Gault0 Known intolerance or allergy to tenofovir disoproxil fumarate, tenofovir alafenamide, emtricitabine, or bictegravir.

8. Currently taking or plans to take prohibited medication while enrolled in the study. (Appendix B: complete list of prohibited medications).

9. Non-English speakers.