Dolutegravir Plus Lamivudine Dual Therapy in Treatment Naïve HIV-1 Patients

This study was a phase II, single-arm, open-label pilot study designed to estimate the
efficacy of dolutegravir (DTG) plus lamivudine (3TC) as initial combination ART
(antiretroviral therapy) in HIV-1 infected treatment naive participants. The target
enrollment was 120 participants with a cap of N=90 participants with screening HIV-1 RNA <=
100,000 copies/mL. The study aimed to enroll >= 20% women. The expected follow-up for each
participant was 52 weeks.

Visits occurred at screening, entry, and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
from study entry. All signs/symptoms within 30 days prior to entry were recorded.
Subsequently, grade 2 or higher rash and all other grade 3 or higher signs and symptoms were
recorded. All participants underwent routine monitoring including plasma HIV-1 RNA levels,
CD4+ cell count, hematology, chemistry, urinalysis, and pregnancy testing (for women of
reproductive potential).

Population-based protease (PR), reverse transcriptase (RT) and integrase genotyping were done
at the time of confirmed virologic failure. Plasma samples were stored for potential future
studies to assess the impact of adherence, drug-resistant minority viral variants, and DTG
exposure on virologic and CD4+ cell count responses to DTG plus 3TC. All participants also
underwent UGT1A1 genotyping.

NOTE: Further information on the eligibility criteria can be found in the study protocol.

Inclusion Criteria:

- HIV-1 infection.

- Plasma HIV-1 RNA ≥1000 copies/mL and <500,000 copies/mL obtained within 90 days prior
to study entry.

- No evidence of any RT, any integrase, or major protease resistance mutation (according
to the 2014 IAS-USA drug resistance mutations list, available at
https://www.iasusa.org/sites/default/files/tam/22-3-642.pdf) based on pre-ARV
(antiretroviral) treatment genotype performed any time prior to study entry.

- ARV treatment drug-naive (defined as no previous ARV treatment at any time prior to
study entry, with the exception of successful post-exposure prophylaxis (PEP) or
pre-exposure prophylaxis (PrEP).

- The following laboratory values obtained within 45 days prior to study entry:

- ANC (absolute neutrophil count) ≥750/mm^3

- Hemoglobin ≥10.0 g/dL

- Platelets ≥ 50,000/mm^3

- Calculated creatinine clearance (CrCl) ≥50 mL/min, as estimated by the
Cockcroft-Gault equation

- AST (aspartate aminotransferase) <5 x ULN (upper limit of normal)

- ALT (alanine aminotransferase) <5x ULN

- Total bilirubin <1.5 x ULN

- Hepatitis B surface antigen negative within 45 days prior to study entry.

- For women with reproductive potential, negative serum or urine pregnancy test at
screening and within 48 hours prior to study entry.

- If participating in sexual activity that could lead to pregnancy, female participants
with reproductive potential must have agreed to use one form of contraceptive as
listed in the protocol while receiving protocol-specified medications and for 30 days
after stopping the medications.

- Ability and willingness of participant or legal representative to provide informed
consent.

Exclusion Criteria:

- Serious illness requiring systemic treatment and/or hospitalization.

- Treatment within 30 days prior to study entry with immune modulators such as systemic
steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF),
erythropoietin, or any investigational therapy.

- Pregnancy or breastfeeding.

- Receipt of systemic cytotoxic chemotherapy or dofetilide.

- Known allergy/sensitivity to any of the study drugs or their formulations.

- Active drug or alcohol use or dependence that may interfere with adherence to study
requirements, in the opinion of the site investigator.

- Active hepatitis C virus (HCV) treatment or anticipated need for treatment within
study period.

- Unstable liver disease (as defined by the presence of ascites, encephalopathy,
coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice),
known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic
gallstones).

- Severe hepatic impairment (Class C) as determined by Child-Pugh classification.