| Eligibility |
Inclusion Criteria:
1. 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.
WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention)
guidelines mandate that confirmation of the initial test result must use a test that
is different from the one used for the initial assessment. More information on this
criterion can be found in the protocol.
2. Currently on continuous combination ART (antiretroviral therapy) for =48 weeks prior
to study entry. This is defined as continuous ART for the 48-week period prior to
study entry with no ART interruption longer than 7 consecutive days.
3. Screening plasma HIV-1 RNA <40 copies/mL within 90 days prior to study entry using a
FDA-approved assay with a quantification limit of 40 copies/mL or lower performed by
any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA)
certification or its equivalent.
4. HIV-1 RNA level <40 copies/mL for at least 48 weeks prior to study entry performed by
any US laboratory that has a CLIA certification or its equivalent.
- NOTE: Single determinations that are between the assay quantification limit and
500 copies/mL (i.e., "blips") are allowed as long as the preceding and subsequent
determinations are below the level of quantification. The screening value may
serve as the subsequent undetectable value following a blip.
5. CD4?/CD8? cell count obtained within 90 days prior to study entry at any US laboratory
that has a CLIA certification or its equivalent.
6. Positive CMV IgG serology, at any time prior to study entry using a FDA-approved assay
at any US laboratory that has a CLIA certification or its equivalent.
- NOTE: If a prior positive CMV IgG serology test is confirmed in the medical
record, a repeat CMV IgG test is not required at screening.
7. The following laboratory values obtained within 90 days prior to study entry by any US
laboratory that has a CLIA certification or its equivalent:
- Hemoglobin >9.0 g/dL
- Platelet count >75,000/mm³
- Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT),
and alkaline phosphatase =3 x ULN (upper limit of normal)
- Total bilirubin =2.5 x ULN
- NOTE: If an individual is taking atazanavir-containing regimen at the time
of screening, a total bilirubin of =5 x ULN is acceptable.
- Estimated Glomerular Filtration Rate (eGFR) >30 mL/min/1.73m² or creatinine
clearance (CrCl) >30 mL/min using the Cockcroft-Gault, EPI-GFR or MDRD equations
located on the DMC website.
8. For individuals assigned female sex at birth and of reproductive potential, negative
serum or urine pregnancy test within 24 hours prior to study entry by any US clinic or
laboratory that has a CLIA certification or its equivalent, or a CLIA Certificate of
Waiver for those performing a point of care (POC)/CLIA-waived test. (Urine test must
have a sensitivity of <25 mlU/mL).
- NOTE: Persons of female sex assigned at birth and of reproductive potential are
defined as having reached menarche and have not been post-menopausal for at least
24 consecutive months (i.e. have had menses within the preceding 24 months), and
have not undergone testosterone therapy for gender alignment or surgical
sterilization such as hysterectomy, bilateral oophorectomy, tubal ligation or
salpingectomy. An individual's report is considered acceptable documentation or
reproductive status.
9. All participants that are participating in sexual activity that could lead to
pregnancy must agree to use contraception throughout the study. At least one of the
following must be used throughout the study:
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Hormone-based contraceptive
- Condoms with or without a spermicide
- NOTE A: Individuals who are not of reproductive potential are not required
to use contraception.
- NOTE B: Sperm-producing participants should refrain from donating sperm
during the treatment period and for at least 90 days after the last dose of
study treatment.
10. Persons age greater than or equal to 40 years.
11. Ability and willingness of individual or legal guardian/representative to provide
informed consent.
Exclusion Criteria:
1. Change in the ART regimen within 12 weeks prior to study entry or intended
modification of ART during the study.
- NOTE: Modifications in the dosage or frequency (i.e. twice a day [bid] to once a
day [qd]) of individual antiretroviral (ARV) drugs during the 12 weeks prior to
study entry are permitted. In addition, the change in formulation (e.g. from
standard formulation to fixed-dose combination) is allowed within 12 weeks prior
to study entry. A within class single drug substitution (e.g. switch from
atazanavir to darunavir, or tenofovir disoproxil fumarate to tenofovir
alafenamide) is allowed within 12 weeks prior to study entry. A switch to any
other nucleoside reverse transcriptase inhibitor (NRTI) from abacavir (or vice
versa) is not permissible. No other changes in ART within the 12 weeks prior to
study entry are permitted.
2. Use of any of the following ARV drugs in current regimen: efavirenz, nevirapine,
etravirine, lopinavir/ritonavir, and once-daily dosing of raltegravir (bid dosing of
raltegravir is acceptable).
3. Two or more HIV-1 RNA determinations >200 copies/mL within 48 weeks prior to study
entry.
4. Any febrile illness (>101°F) within 30 days prior to study entry.
5. Use of drugs with anti-CMV activity within 90 days prior to study entry, with the
exception of standard dose valacyclovir and acyclovir. See the protocol for more
information.
6. Immunosuppressive or immunomodulatory drug use, with the exception of topical,
inhaled, and intranasal corticosteroids within 90 days prior to study entry. See the
protocol for more information.
7. Concomitant use of prohibited medications. See the protocol for more information.
8. Persons who are breastfeeding, pregnant or planning to become pregnant during the
study.
9. Participating in a study where co-enrollment is not allowed.
10. Receipt of any vaccination within 14 days prior to study entry.
11. Presence on screening ECG or a known history of atrial tachycardia (other than sinus
tachycardia). Ventricular tachycardia is also an exclusion criterion.
12. History of cardiomyopathy or congenital heart disease or evidence of advanced
conduction system disease including second degree heart block Mobitz type II, third
degree heart block, AV dissociation or ECG findings that may be suggestive of
predisposition to arrhythmia (i.e. delta wave).
13. Known allergy/sensitivity or any hypersensitivity to components of the study drug or
its formulation.
14. Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements.
15. Acute or serious illness requiring systemic treatment and/or hospitalization within 90
days prior to study entry.
16. Known chronic active hepatitis B virus infection within the last 24 weeks prior to
study entry.
- NOTE: Active is defined as hepatitis B surface antigen (HBsAg) positive and
hepatitis B DNA (HBV DNA) positive. Persons with HBV DNA below level of
quantification (BLQ) for >24 weeks prior to study entry are eligible.
17. Known chronic active hepatitis C within the last 24 weeks prior to study entry.
- NOTE: Active is defined as a detectable plasma hepatitis C virus (HCV) RNA level.
Persons with HCV RNA BLQ for >24 weeks prior to study entry are eligible.
18. Presence of history of conditions that could account for impaired neuropsychological
performance (if present), including head injury with prolonged (>1 hour) loss of
consciousness, central nervous system infection (e.g. encephalitis), severe learning
disability, psychosis, and/or active drug or alcohol use, or dependence that, in the
opinion of the site investigator, would interfere with adherence to study
requirements.
19. History of multi-class HIV drug resistance or intolerance, such that in the opinion of
the investigator, an alternative fully active antiretroviral regimen cannot be
constructed should the participant experience loss of viral suppression on their
current regimen during the study.
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