| Eligibility |
Inclusion Criteria:
- Estimated date of HIV-1 acquisition within 8 weeks of participant's last HVTN 704/HPTN
085 infusion.
- Initiated ART within 28 weeks of HVTN 704/HPTN 085 HIV-1 date of diagnosis.
- Receiving continuous ART for at least 1 year. ART interruptions of up to 7 days and =
90 days prior to enrollment are acceptable. Within- and between-class changes in ART
within the previous year are acceptable.
- If on an NNRTI, willingness and ability to switch to a PI- or INSTI-containing regimen
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 ART
re-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 sexual
activity until after confirmation of viral suppression following ART re-initiation.
- Willingness for CRS staff to contact primary HIV care provider to exchange information
regarding HVTN 804/HPTN 095 and participant medical history.
- Site investigator anticipates that a fully active alternative ART regimen could be
constructed and would be available in the event of virologic failure on the
participant's current ART regimen.
- Access to a participating CRS and willingness to adhere to study visit schedule and to
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 of
understanding of all questionnaire items answered incorrectly.
- Agrees not to enroll in another study of an investigational research agent for the
duration of the participant's trial participation.
Laboratory Inclusion Values:
Immunology/Virology
- HIV-1 infection, with reactive HIV-1 antibody and any Multispot or Geenius HIV-1/HIV-2
results, documented by the HVTN 704/HPTN 085 HIV diagnostic algorithm.
- Plasma HIV-1 RNA = 1,000 copies/mL by any assay, prior to initiating ART.
- CD4+ 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 an VQA-certified
or DAIDS-approved assay and collected:
- at screening, within 90 days prior to enrollment; and
- greater than 9 months prior to the screening HIV-1 RNA.
Hematology
- Hemoglobin (Hgb) = 10.0 g/dL for volunteers who were assigned female sex at birth, =
11.0 g/dL for volunteers who were assigned male sex at birth.
- Absolute neutrophil count (ANC) = 750 cells/mm3
- Platelets = 100,000 cells/mm3
Chemistry
- ALT < 2.5 times the institutional upper limit of normal and 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 human chorionic
gonadotropin (ß-HCG) pregnancy test performed at the screening visit and prior to
enrollment. Persons who are NOT capable of becoming pregnant due to having reached
menopause (no menses for 1 year) or having undergone total hysterectomy or bilateral
oophorectomy or tubal ligation (verified by medical records) are not required to
undergo pregnancy testing.
- Reproductive status: A volunteer who is capable of becoming pregnant must agree to
consistently use effective contraception for sexual activity that could lead to
pregnancy from at least 21 days prior to enrollment through confirmation of viral
suppression following ART re-initiation.
- Volunteers capable of becoming pregnant must also agree not to seek pregnancy through
alternative methods, such as artificial insemination or in vitro fertilization, until
after confirmation of viral suppression following ART re-initiation.
Exclusion Criteria:
1. Any plasma HIV-1 RNA = LLOQ (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 by values < LLOQ and if the blips occur more than 6 months prior
to enrollment.
Note: US volunteers must have results from a CLIA or VQA-approved assay. Non-US sites
must have results from locally available assays that are approved as standard-of-care
by their regional governing bodies.
2. History of AIDS-defining illnesses or US Centers for Disease Control (CDC) Category C
events per the current list on the CDC website (see HVTN 804/HPTN 095 SSP).
3. Autoimmune disease, including Type I diabetes mellitus (Not excluded from
participation: Volunteer with mild, stable and uncomplicated autoimmune disease that
does not require consistent immunosuppressive medication and that, in the judgment of
the site investigator, is likely not subject to exacerbation and likely not to
complicate AE assessments).
4. Immunosuppressive medications received within 6 months before enrollment (Not
exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical
corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course
of oral/parenteral prednisone or equivalent at doses < 60 mg/day and length of therapy
< 11 days with completion at least 30 days prior to enrollment).
5. Blood products received within 120 days before planned ART interruption.
6. Investigational research agents, other than experimental vaccine(s) (See Exclusion
Criterion #7), received within 30 days before planned ART interruption.
7. HIV or non-HIV experimental vaccine(s) received within the last 1 year. Exceptions may
be made by the HVTN 804/HPTN 095 PSRT for vaccines that have subsequently undergone
licensure by the FDA or by the national regulatory authority where the volunteer is
enrolling. For volunteers who have received control/placebo in an experimental vaccine
trial, the HVTN 804/HPTN 095 PSRT will determine eligibility on a 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 804/HPTN 095 PSRT on a
case-by-case basis.
8. Licensed live attenuated vaccines received within 30 days before planned ART
interruption (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV];
varicella; yellow fever; live attenuated influenza vaccine).
9. Licensed vaccines that are not live attenuated vaccines received within 14 days before
planned ART interruption (eg, tetanus, pneumococcal, hepatitis A or B).
10. Receipt of any emergency-use authorized, WHO emergency use listed, licensed or
registered SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccine within
4 weeks before planned ART interruption. Note: SARS-CoV-2 vaccination is not required
for HVTN 804/HPTN 095 eligibility.
11. Significant or unstable cardiac or cerebrovascular disease (eg, angina, congestive
heart failure [CHF], recent cerebrovascular accident [CVA], or myocardial infarction
[MI]).
12. Hepatitis B surface antigen (HBsAg) or positive HCV RNA (Not exclusionary: positive
HCV Ab with negative HCV RNA).
13. Volunteers who have:
- a SARS-CoV-2 positive test (direct viral detection, eg, viral nucleic acid or
antigen detection) =14 days of enrollment, if asymptomatic OR
- unresolved COVID-19 (ie, SARS-CoV-2 positive test AND symptoms) = 14 days of
enrollment (not excluded: individuals with symptoms consistent with residual
sequelae of resolved COVID19, in the clinical judgement of the investigator)
14. Pregnant or breastfeeding
15. Clinically significant medical condition, physical examination findings, clinically
significant abnormal laboratory results, or past medical history with clinically
significant implications for current health. A clinically significant condition or
process 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 establish
venous access;
- A condition that requires active medical intervention or monitoring to avert
grave danger to the volunteer's health or well-being during the study period; or
- Any condition specifically mentioned among the exclusion criteria.
16. Any medical, psychiatric, occupational, or other condition that, in the judgment of
the investigator, would interfere with, or serve as a contraindication to, protocol
adherence, assessment of safety, or a volunteer's ability to give informed consent.
17. Any medical, psychiatric, occupational, or other condition that, in the judgment of
the investigator, could be exacerbated by events associated with protocol
participation, which include: ATI, low-level viremia, subsequent viral rebound, and
ART re-initiation.
18. HIV dementia or other neurologic disease that, in the judgment of the investigator,
would be a contraindication to study participation.
19. Psychiatric condition that precludes compliance with the protocol. Specifically
excluded are persons with psychoses within the past 3 years, ongoing risk for suicide,
or history of suicide attempt or gesture within the past 3 years.
20. Malignancy (Not excluded from participation: Volunteer who has had malignancy excised
surgically and who, in the investigator's judgment, has a reasonable assurance of
sustained cure, or who is unlikely to experience recurrence of malignancy during the
period of the study).
21. Current untreated or incompletely treated active tuberculosis disease or current
latent tuberculosis infection (Not excluded from participation: Volunteer who has
latent tuberculosis infection and is undergoing treatment, with at least one month of
treatment completed)
22. Untreated or incompletely treated syphilis, gonorrhea, or chlamydia infection
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