Analytical Treatment Interruption (ATI) to Assess the Immune System's Ability to Control HIV in Participants Who Became HIV-infected During the HVTN 703/HPTN 081 AMP Study

Inclusion Criteria:

• Estimated date of HIV-1 acquisition within 8 weeks (ie, before or after) havingreceived an HVTN 703/HPTN 081 infusion.

• Initiated ART within 28 weeks of HVTN 703/HPTN 081 date of HIV-1 diagnosis.

• Receiving continuous ART for at least 1 year. ART interruptions of up to 7 days induration and ≥ 90 days prior to enrollment are acceptable. Within- and between-classchanges in ART within the previous year are acceptable.

• If on an NNRTI, willingness and ability to switch to a PI- or INSTI-containingregimen for at least 4 weeks prior to ART interruption.

• Willingness to interrupt ART for up to 24 weeks or up to the time of meeting ARTre-initiation criteria.

• Willingness to re-initiate ART upon meeting study ART re-initiation criteria.

• Willingness to use barrier protection (ie, male or female condoms) for all sexualactivity during ATI and until confirmation of viral suppression following ARTre-initiation.

• Willingness for CRS staff to contact primary HIV care provider to exchangeinformation regarding HVTN 805/HPTN 093 and participant medical history.

• Site investigator anticipates that a fully active alternative ART regimen could beconstructed and would be available in the event of virologic failure on theparticipant's current ART regimen.

• Access to a participating CRS and willingness to adhere to study visit schedule andto be followed for the planned duration of the study.

• Ability and willingness to provide informed consent.

• Assessment of understanding: volunteer demonstrates understanding of this study;completes a questionnaire prior to enrollment with verbal demonstration ofunderstanding of all questionnaire items answered incorrectly.

• Agrees not to enroll in another study of an investigational research agent for theduration of the participant's trial participation.

Laboratory Inclusion Values:

Immunology/Virology

• HIV-1 infection, with reactive HIV-1 antibody and any Multispot or GeeniusHIV-1/HIV-2 results, documented by the HVTN 703/HPTN 081 HIV diagnostic algorithm.

• Plasma HIV-1 RNA ≥ 1,000 copies/mL by any assay, prior to initiating ART.

• CD4+ T cell count ≥ 450 cells/mm3 obtained within 90 days prior to enrollment.

• One plasma HIV-1 RNA below the lower limit of quantitation (LLOQ) of anVQA-certified or DAIDS-approved assay and collected at each of the following:

• at screening, within 90 days prior to enrollment; and

• greater than 9 months prior to the screening HIV-1 RNA. Note: Sites must haveresults from locally available assays that are approved as standard-of-care bytheir regional governing bodies.

Hematology

• Hemoglobin (Hgb) ≥ 10.0 g/dL

• Absolute neutrophil count (ANC) ≥ 750 cells/mm3

• Platelets ≥ 100,000 cells/mm3

Chemistry

• Alanine aminotrasferase (ALT) < 2.5 times the institutional upper limit of normaland direct bilirubin within the institutional range of normal.

• Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2

Reproductive Status

• Volunteers capable of becoming pregnant: negative serum or urine beta humanchorionic gonadotropin (β-HCG) pregnancy test performed at the screening visit andprior to enrollment. Persons who are NOT capable of becoming pregnant due to havingreached menopause (no menses for 1 year) or having undergone total hysterectomy orbilateral oophorectomy or tubal ligation (verified by medical records) are notrequired to undergo pregnancy testing.

• Reproductive status: A volunteer who is capable of becoming pregnant must agree toconsistently use effective contraception (ie, IUD or hormonal) for sexual activitythat could lead to pregnancy from at least 21 days prior to enrollment throughconfirmation of viral suppression following ART re-initiation.

• Volunteers capable of becoming pregnant must also agree not to seek pregnancythrough alternative methods, such as artificial insemination or in vitrofertilization, until after confirmation of viral suppression following ARTre-initiation.

Exclusion Criteria:

• Any plasma HIV-1 RNA ≥ LLOQ of VQA-certified or DAIDS-approved assay (LLOQ: 75, 50, 40, or 20 copies/mL) within 12 months prior to enrollment. NOTE: Two "blips" (ie,plasma HIV-1 RNA > LLOQ) < 400 copies/mL are allowed if preceded and followed byvalues < LLOQ and if the blips occur more than 6 months prior to enrollment. Note:Sites must have results from locally available assays that are approved asstandard-of-care by their regional governing bodies.

• History of AIDS-defining illnesses or US Centers for Disease Control (CDC) CategoryC events per the current list on the CDC website.

• Autoimmune disease, including Type I diabetes mellitus (Not excluded fromparticipation: Volunteer with mild, stable and uncomplicated autoimmune disease thatdoes not require consistent immunosuppressive medication and that, in the judgmentof the site investigator, is likely not subject to exacerbation and likely not tocomplicate AE assessments).

• Immunosuppressive medications received within 6 months before enrollment (Notexclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3]topical corticosteroids for mild, uncomplicated dermatologic condition; or [4] asingle course of oral/parenteral prednisone or equivalent at doses < 60 mg/day andlength of therapy < 11 days with completion at least 30 days prior to enrollment).

• Blood products received within 120 days before planned ART interruption.

• Investigational research agents, other than experimental vaccine(s), received within 30 days before planned ART interruption.

• HIV or non-HIV experimental vaccine(s) received within the last 1 year. Exceptionsmay be made by the HVTN 805/HPTN 093 PSRT for vaccines that have subsequentlyundergone licensure by the FDA or by the national regulatory authority where thevolunteer is enrolling. For volunteers who have received control/placebo in anexperimental vaccine trial, the HVTN 805/HPTN 093 PSRT will determine eligibility ona case-by-case basis. For volunteers who have received an experimental vaccine(s)greater than 1 year ago, eligibility for enrollment will be determined by the HVTN 805/HPTN 093 PSRT on a case-by-case basis.

• Licensed live attenuated vaccines received within 30 days before planned ARTinterruption (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV];varicella; yellow fever; live attenuated influenza vaccine).

• Licensed vaccines that are not live attenuated vaccines received within 14 daysbefore planned ART interruption (eg, tetanus, pneumococcal, hepatitis A or B,influenza).

• Receipt of any emergency-use authorized, WHO emergency use listed, licensed orregistered SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccinewithin 4 weeks before planned ART interruption.

Note: SARS-CoV-2 vaccination is not required for HVTN 805/HPTN 093 eligibility

• Significant or unstable cardiac or cerebrovascular disease (eg, angina, congestiveheart failure [CHF], recent cerebrovascular accident [CVA], or myocardial infarction [MI]).

• Positive Hepatitis B surface antigen (HBsAg) or positive HCV RNA (Not exclusionary:positive HCV Ab with negative HCV RNA).

• Pregnant or breastfeeding

• Volunteers who have:

• a SARS-CoV-2 positive test (direct viral detection, eg, viral nucleic acid orantigen detection) ≤ 14 days of enrollment, if asymptomatic OR

• unresolved COVID-19 (ie, SARS-CoV-2 positive test AND symptoms) ≤ 14 days ofenrollment (not excluded: individuals with symptoms consistent with residualsequelae of resolved COVID-19, in the clinical judgement of the investigator)

• Clinically significant medical condition, physical examination findings, clinicallysignificant abnormal laboratory results, or past medical history with clinicallysignificant implications for current health. A clinically significant condition orprocess includes but is not limited to:

• A process that would affect the immune response;

• A process that would require medication that affects the immune response;

• Any contraindication to repeated blood draws, including inability to establishvenous access;

• A condition that requires active medical intervention or monitoring to avertgrave danger to the volunteer's health or well-being during the study period;or

• Any condition specifically mentioned among the exclusion criteria.

• Any medical, psychiatric, occupational, or other condition that, in the judgment ofthe investigator, would interfere with, or serve as a contraindication to, protocoladherence, assessment of safety, or a volunteer's ability to give informed consent.

• Any medical, psychiatric, occupational, or other condition that, in the judgment ofthe investigator, could be exacerbated by events associated with protocolparticipation, which include: ATI, low-level viremia, subsequent viral rebound, andART re-initiation.

• HIV dementia or other neurologic disease that, in the judgment of the investigator,would be a contraindication to study participation.

• Psychiatric condition that precludes compliance with the protocol. Specificallyexcluded are persons with psychoses within the past 3 years, ongoing risk forsuicide, or history of suicide attempt or gesture within the past 3 years.

• Malignancy (Not excluded from participation: Volunteer who has had malignancyexcised surgically and who, in the investigator's judgment, has a reasonableassurance of sustained cure, or who is unlikely to experience recurrence ofmalignancy during the period of the study).

• Current untreated or incompletely treated active tuberculosis disease or currentlatent tuberculosis infection (Not excluded from participation: Volunteer who haslatent tuberculosis infection and is undergoing treatment, with at least one monthof treatment completed)

• Untreated or incompletely treated syphilis, gonorrhea, or chlamydia infection