Overview

The primary objective of this study is to evaluate uptake and retention of long acting cabotegravir (LA-CAB) also known as Apretude versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) also known as Truvada for PrEP among high-risk women in metro-Orlando through week 48 (to also include reasons for lack of retention in PrEP care)

Eligibility

Inclusion Criteria:

• Aged 18-65 years at the time of signing the informed consent
• Cisgender women with a negative/non-reactive HIV test (for those who choose LA-CAB, a negative or non-reactive HIV Ag/Ab assay and negative qualitative HIV-1 RNA test will be used to confirm negative HIV status, for those who choose TDF/FTC, a negative HIV Ag/Ab assay alone will be used to confirm negative HIV status)
• If insured, must have a stable form of insurance that is expected to continue without significant changes for at least 48 weeks
• If un-or-underinsured, must be enrolled in the study sponsor's assistance program which will provide study medications and study-required laboratory tests at no cost
• Must be at "high-risk" of sexually acquired HIV-1 infection which will be defined as any condomless vaginal or anal sex in the past 6 months plus ≥1 of the following:
  1. Partner living with HIV with unknown viral load
  2. ≥1 sex partner of unknown HIV status
  3. Bacterial STI in the past 6 months (GC/Chlamydia or syphilis)
• Cisgender women

        An individual of child-bearing potential (IOCBP) is eligible to participate if they are not
        pregnant [as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at
        screening and a negative urine hCG test at Day 1 (a local serum hCG test at Day 1 is
        allowed if it can be done, and results obtained, within 24 hours prior to Day 1)], not
        lactating, and at least one of the following conditions applies:
        Non-reproductive potential defined as:
        Pre-menopausal IOCBP with one of the following:
        Documented tubal ligation Documented hysteroscopic tubal occlusion procedure with follow-up
        confirmation of bilateral tubal occlusion Hysterectomy Documented Bilateral Oophorectomy
        Post-menopausal IOCBP defined as 12 months of spontaneous amenorrhea [in questionable cases
        a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels
        consistent with menopause (refer to laboratory reference ranges for confirmatory levels)].
        IOCBP on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be
        required to use one of the highly effective contraception methods if they wish to continue
        their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of
        post-menopausal status prior to study enrollment.
        Reproductive potential and agrees to follow one of the options listed in the Modified List
        of Highly Effective Methods for Avoiding Pregnancy in IOCBP (see Appendix 7) from at least
        14 days prior to the first dose of study medication. Participants will be counseled on the
        recommendation to continue use of a highly effective method of contraception for at least
        14 days after discontinuation of oral CAB and at least 52 weeks after discontinuation of
        LA-CAB due to the unknown risk to the fetus. This discussion will be recorded in the
        participant's source notes.
        The investigator is responsible for ensuring that subjects understand how to properly use
        these methods of contraception. All subjects participating in the study should be counseled
        on safer sexual practices including the use and benefit/risk of effective barrier methods
        (e.g., male condom) and on the risk of STI transmission to an uninfected partner.
        Exclusion Criteria:
          -  IOCBP who are breastfeeding or plan to become pregnant or breastfeed during the study
          -  Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh
             classification
          -  Unstable liver disease (as defined by the presence of ascites, encephalopathy,
             coagulopathy, hypoalbuminaemia, esophageal or gastric varices, or persistent
             jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's
             syndrome or asymptomatic gallstones).
          -  Evidence of Hepatitis B virus (HBV) infection based on the results of testing at
             Screening for Hepatitis B surface antigen (HbsAg), Hepatitis B core antibody
             (antiHBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV DNA as follows:
        Subjects positive for HbsAg are excluded. Subjects negative for anti-HBs but positive for
        anti-HBc (negative HbsAg status) and positive for HBV DNA are excluded.
        Note: Subjects positive for anti-HBc (negative HbsAg status) and positive for antiHBs (past
        and/or current evidence) are immune to HBV and are not excluded. AntiHBc must be either
        total anti-HBc or anti-HBc immunoglobulin G (IgG), and NOT anti-HBc IgM.
        -Evidence of Hepatitis C virus (HCV) infection based on the results of testing at Screening
        for Hepatitis C antibody (HCV Ab) and HCV RNA as follows:
        Subjects positive for HCV Ab and HCV RNA are excluded Subjects positive for HCV Ab with a
        negative HCV RNA test are permitted to enroll
          -  History or presence of allergy or intolerance to the study drugs or their components
             or drugs of their class.
          -  Has a history or current evidence of any condition (including active tuberculosis
             infection), therapy, laboratory abnormality or other circumstance (including drug or
             alcohol use or dependence) that might, in the opinion of the investigator, confound
             the results of the study or interfere with the participant's participation for the
             full duration of the study, such that it is not in the best interest of the
             participant to participate.
          -  Participants receiving any prohibited medication and who are unwilling or unable to
             switch to an alternative medication Participants with a current or anticipated need
             for chronic systemic anticoagulation or a history of known or suspected bleeding
             disorder, including a history of prolonged bleeding
             **Please note this protocol does not exclude participants who have previously received
             PrEP medications including IM LA-CAB or oral TDF/FTC
          -  ALT ≥5x ULN, OR ALT ≥3xULN and bilirubin >=1.5xULN (with >35% direct bilirubin)
          -  CreCl<50 ml/min for those who elect to start TDF/FTC
          -  Any other screening grade 3 or 4 lab abnormalities that are unexplained or deemed by
             the investigator to be a contraindication for study participation