| Eligibility |
Step 1 Inclusion Criteria:
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
confirmed by a licensed Western blot or a second antibody test by a method other than
the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
NOTE: The term "licensed" refers to a US FDA-approved kit, which is required for all IND
studies, or for sites located in countries other than the United States, a kit that has
been certified or licensed by an oversight body within that country and validated
internally.
- Plasma HIV-1 RNA >1000 copies/mL by any assay obtained prior to initiating ART. NOTE:
Documentation or candidate recall is acceptable.
- For Cohort A participants, ART initiated during chronic infection (e.g., more than 6
months after estimated date of infection, or as determined by site investigator, study
team, or available medical records).
- For Cohort B, diagnosis of acute HIV infection (AHI) as defined by the criteria listed
below.
Fiebig Staging Criteria (must be source documented):
- Fiebig I-II: E/CIA negative, HIV-1 RNA or p24 antigen positive, and negative or
indeterminate Western blot, if performed
- Fiebig III-IV: Reactive HIV-1 antibody and negative or indeterminate results on the
Western blot or Geenius HIV-1/HIV-2
- Fiebig V: Reactive HIV-1 antibody and positive Western blot or Geenius HIV-1/HIV-2
without p31 band NOTE A: ART must have been initiated more than 10 days after Fiebig
I-II diagnosis and less than 90 days after Fiebig V diagnosis to qualify for Cohort B.
NOTE B: Candidates who were diagnosed with Fiebig I-II AHI must have had a positive
HIV-1 RNA test or subsequently have had a positive Western blot if no positive HIV-1
RNA test was available.
- Receiving continuous ART for at least 2 years and on any NNRTI-, PI-, or
INSTI-containing regimen.
NOTE A: ART interruptions of up to 7 days and at least 90 days prior to entry are
acceptable.
NOTE B: Within- and between-class changes in ART within the previous 2 years are
acceptable.
- For candidates whose ART includes an NNRTI, willingness and ability to change to a PI-
or INSTI-containing regimen for at least 4 weeks prior to ART interruption and the
local availability of such a regimen.
- Nadir CD4+ cell count =200 cells/mm3.
NOTE: Candidate recall or documentation is acceptable.
- CD4+ cell count =500 cells/mm3 obtained within 90 days prior to study entry in a US
laboratory that has is compliant with Clinical Laboratory Improvement Amendments
(CLIA) or its equivalent or in any network approved non-US laboratory that operates in
accordance with Good Clinical Laboratory Practices (GCLP) and participates in
appropriate external quality assurance (EQA) programs.
- One documented plasma HIV-1 RNA that is below the limit of detection of an
FDA-approved assays (limit of detection: 75, 50, 40, or 20 copies/mL) between 12 and
24 months prior to the screening HIV-1 RNA and one documented HIV-1 RNA that is below
the limit of detection of the FDA-approved assays (limit of detection: 75, 50, 40, or
20 copies/mL) collected fewer than 12 months prior to the screening HIV-1 RNA.
- Plasma HIV-1 RNA level below the limit of assay quantification within 90 days prior to
entry.
- The following laboratory values obtained within 90 days prior to entry by any US
laboratory that is compliant with CLIA or its equivalent or in any network approved
non-US laboratory that operates in accordance with GCLP and participates in
appropriate EQA programs.
Absolute neutrophil count (ANC) =750 cells/mm3 Hemoglobin =11.0 g/dL for men and =10.0 g/dL
for women Platelet count =100,000/mm3 Creatinine =1.5 mg/dL Aspartate aminotransferase
(AST) (SGOT) =1.5x upper limit of normal (ULN) Alanine aminotransferase (ALT) (SGPT) =1.5x
ULN
- HCV antibody negative result obtained within 90 days prior to study entry or, if the
HCV antibody result is positive, a negative HCV RNA result within 90 days prior to
study entry and no positive HCV RNA result within 24 weeks prior to entry.
- Ability and willingness of participant to provide informed consent.
- Willingness to have blood samples collected and stored indefinitely and used for
HIV-related research purposes.
- For females of reproductive potential (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, or
bilateral oophorectomy and/or bilateral salpingectomy), a negative serum or urine
pregnancy test within 48 hours prior to study entry by any clinic or laboratory that
has a CLIA certification or its equivalent, or is using a point of care CLIA-waived
test, or at any network approved non-US laboratory or clinic that operates in
accordance with Good Clinical Laboratory Practices and participates in appropriate
external quality assurance programs.
NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, bilateral
salpingectomy, tubal micro-inserts, partner who has undergone vasectomy, and menopause is
participant-reported history.
- All participants must agree to use barrier protection (e.g., condoms, dental dams) for
all sexual activity throughout the entire course of the study to prevent HIV
transmission.
- All participants must agree not to participate in the conception process (e.g., active
attempt to become pregnant or to impregnate, sperm donation, or in vitro
fertilization). If participating in sexual activity that could lead to pregnancy, the
participant/partner must use at least two reliable forms of contraceptives (e.g.,
condoms, with or without a spermicidal agent; a diaphragm or cervical cap with
spermicide; an IUD; hormone-based contraception), with at least one being a barrier
method, during the study.
- 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.
- Absence of either active hepatitis B virus (HBV) infection, indicated by a negative
hepatitis B surface antigen (HBsAg) or HBV viral load assays within 90 days prior to
entry or known chronic hepatitis B infection based on a previously positive HBV DNA or
positive HBsAg without a subsequent positive hepatitis B surface antibody (HBsAb).
Step 1 Exclusion Criteria:
- Any plasma HIV-1 RNA at or above the limit of detection of the FDA-approved assays
(limit of detection: 75, 50, 40, or 20 copies/mL) within 24 months prior to entry.
NOTE: A single unconfirmed "blip" (i.e., plasma HIV-1 RNA over limit of detection but <200
copies/mL) is allowed if preceded and followed by values below the limit of detection and
if the blip occurred more than 6 months prior to study entry.
- Currently breastfeeding or plans on breastfeeding during the course of the study or is
pregnant.
- Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements.
- Acute or serious illness, in the opinion of the site investigator, requiring systemic
treatment and/or hospitalization within 60 days prior to entry.
- Any history of an AIDS-defining illness using the current list on the U.S. Centers for
Disease Control and Prevention (CDC)'s website.
- Receipt of any study-defined prohibited medications within 6 months prior to entry.
- Prior history of difficulty establishing venous access or current contraindication for
leukapheresis, in the opinion of the site investigator and based on assessments.
- Receipt of any vaccination within 1 week prior to entry.
NOTE: The entry visit must be scheduled to ensure that 1 week has elapsed after any
vaccination.
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