CCTG 595 is a controlled, open-label, two-arm, randomized (1:1) clinical demonstration project to determine if the use of a text-message based adherence intervention (iTAB) improves retention and adherence to PrEP compared to standard of care (SoC) PrEP delivery.

A total of 400 HIV-uninfected men who have sex with men (MSM)and male to female (M to F) transgender individuals with recent high-risk transmission behavior will be enrolled into the study. Each subject will be followed for up to 48 weeks after enrollment of the last subject. The primary endpoint will be measured at 48 weeks.

All subjects will start PrEP with TDF + FTC fixed dose combination given once daily. Subjects will be randomized (1:1) to either the iTAB text messaging adherence reminder intervention with SoC or the SoC alone arm. Subjects placed into the iTAB intervention arm will receive a personalized, automated texting system to maintain adherence and retention. Both groups will receive access to PrEP in accordance with standardized comprehensive methods of prescribing, risk reduction counseling, adherence counseling, and clinical assessments that include safety monitoring, as well as HIV and STD screening.

TDF 300 mg + FTC 200 mg fixed dose combination will be given orally once daily starting at the baseline visit (month 0) and continued throughout the study.

Inclusion Criteria:

• Man or transgender M to F who has sex with men.

• Age 18 years or older.

• Subjects must have substantial ongoing risk of acquisition of HIV as evident by one or more of the following:

  • Has at least one HIV infected sexual partner for ≥4 weeks.
  • No condom use during anal intercourse with ≥3 male sex partners who are HIV-positive or of unknown HIV status during the last 3 months.
  • No condom use during anal sex with ≥1 male partner and STI diagnosis during the last 3 months.

• Negative for HIV infection by rapid HIV test and confirmed negative by NAT or other sensitive method such as antibody- antigen test.

• Acceptable laboratory values in the past 30 days:

  • Calculated creatinine clearance of at least 60 mL/min by the Cockcroft-Gault formula (eCcr (male) in mL/min = [(140 - age in years) x (lean body weight in kg)] / (72 x serum creatinine in mg/dL)
  • Alanine aminotransferase (ALT) and/ or aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN)
  • Hemoglobin > 9 g/dL
  • Absolute neutrophil count > 750/ mm3
  • Platelets > 75,000/ mm3

Exclusion Criteria:

• Unable to give informed consent.

• Active hepatitis B (positive hepatitis B surface antigen (HBSAg) or HBSAg negative/ HB core antibody positive/ HBV PCR positive).

• Has substantial medical condition, that in the opinion of the investigator would preclude participation, as defined by

  • cardiovascular condition that may lead to an increased risk of complication if placed on study drugs.
  • gastrointestinal condition that would impair absorption of study drugs.
  • neurological or psychiatric condition that would significantly impair the ability to adhere to PrEP.
  • calculated GFR < 60 mL/min.
  • alcohol or drug abuse or dependence that would significantly impair the ability to adhere to PrEP (only for those with severe impairment).
  • other medical condition that would unacceptably increase the risk of harm from study drug or significantly impair the ability to adhere to PrEP.

• Suspected sensitivity or allergy to the study drug or any of its components.

• Currently using an essential product or medication that interacts with the study drug such as the following:

  • ART (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents)

  • Agents with known nephrotoxic potential:

    • aminoglycoside antibiotics (including gentamicin)
    • IV amphotericin B
    • cidofovir
    • cisplatin
    • foscarnet
    • IV pentamidine
    • IV vancomycin
    • oral or IV gancyclovir
    • other agents with significant nephrotoxic potential

  • Drugs that slow renal excretion

    • Probenecid

  • Immune system modulators

    • Systemic chemotherapeutic agents (i.e. cancer treatment medications)
    • Ongoing systemic corticosteroids (with the exception of short courses of tapering steroid doses for asthma or other self- limited condition).
    • Interleukin-2 (IL-2)
    • Interferon (alpha, beta, or gamma)

  • Other agent known to have a significant interaction with TDF or FTC

  • Proteinuria 2+ or greater by urine dipstick

  • Signs or symptoms suggestive of acute HIV infection

  • Any other reason or condition that in the opinion of the investigator would interfere with participation, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Up to end of follow up for participants 0-120 weeks

Discontinuation of PrEP may be for valid reasons for not needing prevention of HIV due to not being sexually active

Group 1: PrEP daily, HIV/STI screening, adherence and risk behavior counseling, and safety monitoring Group 2: PrEP daily, HIV/STI screening, adherence and risk behavior counseling, and safety monitoring as well as iTAB text adherence reminders