The DART DELIVER-02 Study

Inclusion Criteria

• •1. HIV infection initially documented by at least one of the following at any time prior to study entry:
• •* any licensed rapid HIV test
• •* HIV antibody test
• •* HIV Ag/Ab assay
• •…and documented confirmation by at least one of the following at any time prior to study entry:
• •* licensed Western blot of HIV ½ antibody differentiation immunoassay
• •* a second antibody test by a method other than the initial rapid HIV and/or HIV antibody assay
• •* HIV-1 antigen, plasma HIV-1 RNA viral assay.
• •2. Ages ≥ 18 to ≤ 65 years old
• •3. Able and willing to give written informed consent.
• •4. Able and willing to stay in contact with site during the duration of the trial
• •5. Able and willing to provide adequate locator information.
• •6. Able and willing to comply with all study requirements through duration of the trial.
• •7. Continuous ART for a minimum of 24 months prior to screening, defined as not missing more than 9 consecutive days in the last 3 months prior to screening.
• •8. No change in any ART medication in the 30 days prior to screening.
• •9. Permitted ART regimens include:
• •• At least 3 ART agents (not counting ritonavir or cobicistat as one of the agents if less than a 200 mg total daily dose). One of the agents must include an integrase inhibitor, NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitors), or a boosted-PI (protease inhibitor).
• •OR
• •• Two (2) ART agents in which one of the agents is either a boosted protease inhibitor or an integrase inhibitor.
• •Note: Other potent fully suppressive antiretroviral combinations will be considered on a case-by-case basis.
• •10. Participants must be determined to have an alternative ART regimen that can be constructed to assure availability of an effective option if assigned to Arm B and TTI leads to selection of virus resistant to the current regimen.
• •11. Ability and willingness of participant to continue ART throughout the study or temporarily discontinue ART for up to 8 weeks (for Arm B) under closely monitored supervision.
• •12. Plasma HIV-1 RNA \<50 copies/mL at 2 time points in the 24 months prior to screening and never ≥50 copies/mL on 2 consecutive time points in the last 24 months.
• •13. No HIV RNA ≥200 copies/mL in the 6 months prior to screening.
• •14. CD4 cell count ≥ 400 cells/mm3 performed at screening.
• •15. At US sites, Hepatitis C (HCV) antibody negative result at screening or, if the participant is HCV antibody positive, a negative HCV RNA at screening; at Kenyan sites, participants must be HCV antibody negative at screening.
• •16. Hepatitis B surface antigen (HBsAg) negative at screening.
• •17. Women of child-bearing potential must have a negative serum pregnancy test with a sensitivity of at least 25 milli-international unit (mIU) per milliliter at screening Note: Women of child-bearing potential is defined as women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy
• •18. For participants with partners who do not have HIV or HIV status unknown, willingness to abstain from sexual intercourse, use a condom, and/or advise partner(s) to use pre-exposure prophylaxis (PrEP) consistently during the study TTI and until plasma HIV-1 RNA is \<200 copies/mL if assigned to Arm B.
• •19. All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) while on study and for 6 months after their last investigational product (IP) intervention.
• •20. All men and women participating in sexual activity that could lead to pregnancy must agree to consistently use at least one of the following forms of birth control for at least 21 days prior to Visit 3 (Day 0) and for 6 months after their last IP intervention.
• •* Condoms (internal or external) with or without a spermicidal agent
• •* Diaphragm or cervical cap with spermicide
• •* Intrauterine device (IUD)
• •* Tubal ligation
• •* Hormone-based contraceptive
• •21. Agrees not to enroll on another study of an investigational agent during the study period, defined as any unlicensed investigational drug not yet approved for use in humans.
• •22. Willingness to defer live vaccinations (e.g., varicella, measles, mumps, rubella (MMR), yellow fever, oral polio, Mpox) from 30 days prior to enrollment through week 16.
• •23. Willingness to defer routine vaccination, including influenza, from 14 days prior to enrollment through Week 16 of the study.
• •Note: Individuals who require vaccination will delay enrollment until 14 days after vaccination.
• •24. Agrees to refrain from blood donation during the course of the study.
• •25. Participants with Type 2 diabetes must have a hemoglobin A1C \<8 or a fasting glucose ≤ 125 mg/dL; mmol/L at screening.
• •26. Adequate organ function as indicated by the laboratory values in Table 7 of the protocol.