Inclusion Criteria:
* Age ≥18 and ≤30 years old
* Willing to undergo urine pregnancy tests
* Has understood the information provided and has provided written informed consent before any study-related procedures are performed.
* HIV uninfected based on negative HIV rapid tests, according to Kenyan national algorithm
* Normal renal function (estimated glomerular filtration rate \>60 mL/min)
* Hepatitis B surface Ag negative
* No active clinically significant medical or psychiatric conditions that, in the opinion of the investigators, would interfere with study participation
* Lack of severe anemia (Hemoglobin \>10 g/dL)
* Willing to use DOT and come to clinic frequently for DOT PrEP for at least 10 weeks
* Willing to have home visits for follow up
* Has access to an active smartphone to allow off-site observation of dosing if unable to come to the clinic or as determined by the study staff, the participant resides in close location to clinic to permit home visit if unable to come to the clinic. i.e., potential participants without a smartphone may be enrolled in the study if investigator determines that the participant resides within reasonable distance from the clinic that would permit home visit id the participant misses their visit.
* Intention to stay within the study site's catchment area for at least 10 weeks.
* Resides or works in catchment area with high speed internet coverage to permit video streaming
* Not pregnant or breast feeding
* Willing to use effective contraception during the study period.
* At low risk for HIV. In Kenya, national guidelines define substantial risk for HIV and recommend PrEP be an option for individuals reporting: partner of HIV-infected person not on ART or on ART for \<6 months, \>1 partner of unknown status, transactional sex, recent STI, recurrent PEP use, inconsistent condom use, or injection drug use. So, non-pregnant cisgender women reporting any of these factors will not be eligible for the study but will be linked for PrEP at clinic of choice including at Thika Site itself.
* Willing to be randomized to non-daily PrEP and come to clinic frequently for DOT PrEP
* Willingness and ability to be abstinent for at least 7 days after each vaginal biopsy visit.
Exclusion Criteria:
* Inability to give informed consent
* Positive screening HIV+ as determined by standard rapid serologic assays or suspected acute HIV infection in the opinion of the clinician. (example signs and symptoms of acute HIV infection include combinations of fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and adenopathy cervical or inguinal)
* Positive HBV surface antigen test at screening
* Calculated creatinine clearance \<60 ml/min.
* Any laboratory value or uncontrolled medical conditions that, in the opinion of the investigators, would interfere with the study conditions such as, heart disease and/or cancer.
* Prohibited concomitant medications are: investigational agents (within 30 days of enrollment), aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir (\>800mg acyclovir or \>500mg valacyclovir for \>7 days), cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications including TAF®, TRUVADA®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and tenofovir, respectively.
* Current or past use of PrEP (pre-exposure prophylaxis)
* Not willing to have home visits
* Pregnancy or plan to become pregnant in the next 6 months or unwillingness to use birth control
* Current breastfeeding
* High risk of HIV infection (for example: sexually active with an HIV infected partner; engages in condomless intercourse with HIV-infected partners or partner of unknown status during the study; females who exchange sex for money, shelter, or gifts; active injection drug use or during the last 12 months; newly diagnosed sexually transmitted infections in last 6 months.
