| Eligibility |
Inclusion Criteria:
- Males and females at least 18 but no more than 65 years of age at study entry.
- Ability and willingness of participant or legal guardian/representative to provide
informed consent.
- Weight =40 kg and a body mass index (BMI) of greater than 18.5 kg/m^2.
- Documentation of HIV-1 infection status, as below:
- HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test
kit at any time prior to 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 or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral
loads of >1,000 copies/mL are also acceptable as documentation of HIV-1
infection.
- Note A: The term "licensed" refers to a US Food and Drug Administration
(FDA)-approved kit, which is required for all investigational new drug (IND)
studies, or for sites that are 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. Non-US sites are encouraged to use US
FDA-approved methods for IND studies.
- Note B: World Health Organization (WHO) and Centers for Disease Control and
Prevention (CDC) guidelines mandate that confirmation of the initial test result
must use a test that is different from the one used for the initial assessment. A
reactive initial rapid test should be confirmed by either another type of rapid
assay or an E/CIA that is based on a different antigen preparation and/or
different test principle (e.g., indirect versus competitive), or a Western blot
or a plasma HIV-1 RNA viral load.
- HIV-1 plasma viral load <50 copies/mL obtained within 30 days prior to study entry by
any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA)
certification or its equivalent, or at any network-approved non-US laboratory that is
Virology Quality Assessment (VQA) certified.
- At US sites: Evidence of LTBI by tuberculin skin test (TST) reactivity =5 mm, or a
positive interferon gamma release assay (IGRA) at any time prior to study entry.
- At non-US sites: Indication for LTBI treatment according to WHO latent TB
guidelines (Note: TST/IGRA results not required).
- On a stable once daily DTG (50 mg) based ART with once daily 2 NRTIs and
- with at least 28 total days of DTG and NRTI dosing prior to study entry
- with no gaps in self-reported DTG and NRTI adherence of more than 3 consecutive
days in the 28 days prior to study entry
- with no intention to change ART for the duration of the study
- NOTE A: Participants who switch from another ART regimen to DTG to meet
eligibility requirements for this study will be eligible to enroll as long as the
ART is switched at least 28 days prior to study entry.
- Chest radiograph or chest computed tomography (CT) scan performed within 30 days prior
to study entry without evidence of active TB.
- The following laboratory values obtained within 30 days prior to study entry by any US
laboratory that has a CLIA certification or its equivalent, or at any network approved
non-US laboratory that operates in accordance with Good Clinical Laboratory Practice
(GCLP) and participates in appropriate external quality assurance programs.
- Absolute neutrophil count (ANC) >750 cells/mm^3
- Hemoglobin =7.4 g/dL
- Platelet count =50,000/mm^3
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
<2.5 X the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) <2.5
X ULN
- Total bilirubin =1.5 x ULN
- Creatinine <1.3× ULN
- For females of reproductive potential, negative serum or urine pregnancy test at
Screening within 30 days prior to entry and within 48 hours prior to entry by any US
clinic or laboratory that has a CLIA certification or its equivalent, or is using a
point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or
clinic that operates in accordance with GCLP and participates in appropriate external
quality assurance programs.
- NOTE A: If screening visit occurs within 48 hours prior to entry, only one test
will occur prior to entry.
- NOTE B: Urine test must have a sensitivity of 15-25 mIU/mL.
- Female participants of reproductive potential must agree not to participate in the
conception process (i.e., active attempt to become pregnant, in vitro fertilization),
and if participating in sexual activity that could lead to pregnancy, must agree to
use one reliable nonhormonal method of contraception, as listed below, while on study
treatment and through study completion.
- Acceptable forms of contraception include:
- Intrauterine device (IUD) or intrauterine system
- Cervical cap with spermicide
- Diaphragm with spermicide
- NOTE A: Condoms (male or female) with or without a spermicidal agent are not
acceptable, as they are not sufficiently reliable.
- NOTE B: Participant-reported history is acceptable documentation of menopause
(i.e., at least 1 year amenorrheic), hysterectomy, or bilateral oophorectomy or
bilateral tubal ligation; these candidates are considered not of reproductive
potential and are eligible without the required use of contraception.
Exclusion Criteria:
- Breastfeeding, pregnancy, or plans to become pregnant.
- Known allergy/sensitivity or any hypersensitivity to components of the study drugs, or
their formulations.
- Presence of any confirmed or probable active TB based on criteria listed in the
current AIDS Clinical Trials Group (ACTG) Diagnosis Appendix at screening.
- History of rifamycin-monoresistant, INH-monoresistent, multi-drug resistant (MDR) or
extensively-drug resistant (XDR) TB at any time prior to study entry
- Known exposure to rifamycin-monoresistant, INH-monoresistant, MDR- or XDR-TB (e.g.,
household member of a person with rifamycin-monoresistant, INH monoresistant, MDR- or
XDR-TB) at any time prior to study entry by participant self report or medical
records.
- History of peripheral neuropathy Grade =2 according to the Division of AIDS Table for
Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table),
Corrected Version 2.1, July 2017, which can be found on the DAIDS RSC website at
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.
- 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 requiring systemic treatment and/or hospitalization within 7
days prior to study entry.
- Known cirrhosis, a history of decompensated liver disease (ascites, hepatic
encephalopathy, or esophageal varices) or current Child Pugh Class B or C hepatic
impairment.
- Note: Refer to the study protocol for Child Pugh scoring and classification
table.
- Initiated, discontinued, or changed doses of drugs that are P-glycoprotein (PGP)
inducers, that are P-glycoprotein (PGP) inhibitors,or that are known to have drug
interactions with DTG, within 30 days prior to study entry.
- Note: Refer to the list of prohibited and precautionary medications in the study
protocol.
- Known porphyria at any time prior to study entry.
- Receipt of any other antiretroviral therapy other than DTG and 2 NRTI within 28 days
prior to study entry.
- Receipt of TAF within 28 days prior to study entry.
- Documented resistance that may confer reduced susceptibility to DTG, at any time prior
to study entry. This includes the following INSTI mutations: Q148 substitutions, T66A,
L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, G193E/R, or N155H.
- Clinically suspected INSTI resistance, at any time prior to study entry, as evidenced
by prior receipt of INSTI containing ART, during which time two or more HIV-1 RNA
levels of >200 copies/mL were observed after having attained virologic suppression to
<200 copies/mL and without known interruption.
- Consumption of >3 alcohol beverages on any day within 30 days prior to entry.
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