A Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults

1. HIV-1 infected adults >=18 years of age (or older, if required by local
regulations), at the time of signing the informed consent.
2. Screening plasma HIV-1 RNA of 1000 c/mL to <=100,000 c/mL. If an independent
review of accumulated data from other clinical trials investigating the DTG
plus 3TC dual regimen is supportive of the DTG plus 3TC treatment regimen,
enrolment will be opened to subjects with Screening plasma HIV-1 RNA of 1000
c/mL to <=500,000 c/mL;
3. Antiretroviral-naïve (defined as <=10 days of prior therapy with any
antiretroviral agent following a diagnosis of HIV-1 infection). Subjects who
received HIV postexposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP)
in the past are allowed as long as the last PEP/PrEP dose was >1 year from HIV
diagnosis or there is documented HIV seronegativity between the last
prophylactic dose and the date of HIV diagnosis.
4.Male or female.
A female subject is eligible to participate if she is not pregnant as
confirmed by a negative serum human chorionic gonadotrophin (hCG)
test at Screening and negative urine test at Baseline), not lactating, and
at least one of the following conditions applies:
a.Non-reproductive potential defined as:
•Pre-menopausal females with one of the following:
•Documented tubal ligation
•Documented hysteroscopic tubal occlusion procedure with follow-up
confirmation of bilateral tubal occlusion
•Hysterectomy
•Documented Bilateral Oophorectomy
•Postmenopausal defined as 12 months of spontaneous amenorrhea and
>=45 years of age [in questionable cases a blood sample with
simultaneous follicle stimulating hormone (FSH) and oestradiol levels
consistent with menopause is confirmatory (refer to laboratory
reference ranges for confirmatory levels)]. Females on hormone
replacement therapy (HRT) and whose menopausal status is in doubt
will be required to use one of the highly effective contraception methods
if they wish to continue their HRT during the study. Otherwise, they
must discontinue HRT to allow confirmation of post-menopausal status
prior to study enrolment.
b.Reproductive potential and agrees to follow one of the options listed in
the Modified List of Highly Effective Methods for Avoiding Pregnancy in
Females of Reproductive Potential (FRP) (see Appendix 9, Section
12.9.1) from 30 days prior to the first dose of study medication and for
at least 2 weeks after the last dose of study
medication.
The investigator is responsible for ensuring that subjects understand
how to properly use these methods of contraception.
All subjects participating in the study should also be counselled on safer
sexual practices, including the use and benefit/risk of effective barrier
methods (e.g. male condom), and on the risk of HIV transmission to an
uninfected partner.
5. Subject or the subject*s legal representative capable of giving signed
informed consent as described in Section 10.2 which includes compliance with
the requirements and restrictions listed in the consent form and in this
protocol.

1. Women who are breastfeeding or plan to become pregnant or breastfeed during
the study;
2. Any evidence of an active Centers for Disease Control and Prevention (CDC)
Stage 3 disease [CDC, 2014], except cutaneous Kaposi*s sarcoma not requiring
systemic therapy and historical or current CD4 cell counts less than 200
cells/mm3.
3. Subjects with severe hepatic impairment (Class C) as determined by
Child-Pugh classification;
4. Unstable liver disease (as defined by the presence of ascites,
encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices,
or persistent jaundice), cirrhosis, known biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones);
5. Evidence of HBV infection based on the results of testing at Screening for
HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody
(anti-HBs or HBsAb), and HBV DNA as follows:
• Subjects positive for HBsAg are excluded;
• Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg
status)
and positive for HBV DNA are excluded.
NOTE: Subjects positive for anti-HBc (negative HBsAg status) and positive for
anti- HBs (past and/or current evidence) are immune to HBV and are not excluded.
6. Anticipated need for any HCV therapy during the first 48 weeks of the study
and for HCV therapy based on interferon or any drugs that have a potential for
adverse drug:drug interactions with study treatment throughout the entire study
period;
7. Untreated syphilis infection (positive rapid plasma reagin [RPR] at
Screening without clear documentation of treatment). Subjects who are at least
14 days post completed treatment are eligible.
8. History or presence of allergy or intolerance to the study drugs or their
components or drugs of their class;
9. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell
carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or
cervical, anal or penile intraepithelial neoplasia; other localised
malignancies require agreement between the investigator and the Study Medical
Monitor for inclusion of the subject.
10. Subjects who in the investigator*s judgment, poses a significant
suicidality risk. Recent history of suicidal behaviour and/or suicidal ideation
may be considered as evidence of serious suicide risk.
11. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of
Screening;
12. Treatment with any of the following agents within 28 days of Screening
i. radiation therapy,
ii. cytotoxic chemotherapeutic agents,
iii. any systemic immune suppressant;
13. Treatment with any agent, except recognised ART as allowed above (inclusion
criterion 3.), with documented activity against HIV-1 in vitro within 28 days
of first dose of study treatment;
14. Exposure to an experimental drug or experimental vaccine within either 28
days, 5 half-lives of the test agent, or twice the duration of the biological
effect of the test agent, whichever is longer, prior to the first dose of study
treatment.
15. Subjects enrolled in France (and other countries as required by local
regulations or ethics committees/IRBs): the subject has participated in any
study using an investigational drug during the previous 60 days or 5
half-lives, or twice the duration of the biological effect of the experimental
drug or vaccine, whichever is longer, prior to screening for the study or the
subject will participate simultaneously in another clinical study.
16. Any evidence of pre-existing viral resistance based on the presence of any
major resistance-associated mutation [IAS-USA, 2014] in the Screening result
or, if known, in any historical resistance test result. NOTE: retests of
disqualifying Screening genotypes are not allowed.
17. Any verified Grade 4 laboratory abnormality. A single repeat test is
allowed during the Screening period to verify a result.
18. Any acute laboratory abnormality at Screening, which, in the opinion of the
Investigator, would preclude the subject*s participation in the study of an
investigational compound.
19. Alanine aminotransferase (ALT) >=5 times the upper limit of normal (ULN) or
ALT >=3 x ULN and bilirubin >=1.5 x ULN (with >35% direct bilirubin);
20. Creatinine clearance of <50 mL/min/1.73 m2 via the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) method.