Clinical trial NCT02105987 (phase 3, status: completed)
Conditions: infection, human immunodeficiency virus
ICD codes: Z21
Drugs: abc/dtg/3tc fdc, ongoing cart regimen
SMILES: NC1=NC(=O)N(C=C1)[C@@H]1CS[C@H](CO)O1, CCO
Eligibility criteria:

        Inclusion Criteria:

          -  Be able to understand and comply with protocol requirements, instructions, and
             restrictions;

          -  Be likely to complete the study as planned;

          -  Be considered appropriate candidates for participation in an investigative clinical
             trial with oral medication (e.g., no active substance abuse, acute major organ
             disease, or planned long-term work assignments out of the country, etc.).

          -  Signed and dated written informed consent is obtained from the subject or the
             subject's legal representative prior to screening

          -  HIV-1 infected men or women >=18 years of age;

          -  A female may be eligible to enter and participate in the study if she: a. Is of
             non-childbearing potential either defined as post-menopausal (12 months of spontaneous
             amenorrhea and >=45 years of age) or physically incapable of becoming pregnant with
             documented tubal ligation, hysterectomy, or bilateral oophorectomy or,

          -  A female may be eligible to enter and participate in the study if she: b. Is of
             childbearing potential with a negative pregnancy test at both Screening and Day 1 and
             agrees to use one of the following methods of contraception to avoid pregnancy:
             Complete abstinence from intercourse from 2 weeks prior to administration of study
             drug, throughout the study, and for at least 2 weeks after discontinuation of all
             study drugs; Double barrier method (e.g., male condom/spermicide, male
             condom/diaphragm, diaphragm/spermicide); Any intrauterine device (IUD) with published
             data showing that the expected failure rate is <1% per year ; Male partner
             sterilization prior to the female subject's entry into the study and this male is the
             sole partner for that subject; Approved hormonal contraception for subjects randomly
             assigned to the ABC/DTG/3TC arm or approved hormonal contraception plus a barrier
             method for subjects assigned to continued antiretroviral therapy arm; Any other method
             with published data showing that the expected failure rate is <1% per year.

          -  Any contraception method must be used consistently, in accordance with the approved
             product label and for at least 2 weeks after discontinuation of study drug. A
             childbearing potential female subject who starts the study using complete abstinence
             as her contraceptive method and decides to become sexually active must use the double
             barrier method either as a bridge to an approved hormonal contraception (if possible)
             or as a method of choice to be maintained from that moment onwards.

          -  All subjects participating in the study should be counselled on safer sexual practices
             including the use of effective barrier methods (e.g., male condom/spermicide).

          -  Within the last year, 2 consecutive plasma HIV-1 Ribonucleic acid (RNA) measurements
             <50 copies/millilitres (c/mL) and plasma HIV-1 RNA<50 c/mL at Screening (<75 b
             Deoxyribonucleic acid [bDNA] is considered equal to <50 c/mL); Subjects who present at
             initial screening with a viral load between 50 to 200 c/mL can be retested once within
             the screening period.

          -  Must be on current regimen (whether first or second line Combination antiretroviral
             therapy [cART]) for at least 6 months prior to Screening;

          -  Acceptable stable cART regimens prior to Screening include: • Boosted PI (or
             Atazanavir [ATV]) unboosted) + 2 NRTIs, NNRTI + 2 NRTIs, • INI + 2 NRTIs. For subjects
             on an INI, their INI at Screening must be RAL or Elvitegravir (EVG)

          -  Any switch to a second line regimen, defined as change of a single drug or multiple
             drugs simultaneously, must have occurred due to tolerability and/or safety concerns.

          -  Subject must have achieved plasma HIV-1 RNA level <50 c/mL within 6 months of start of
             initial cART regimen with no plasma HIV-1 RNA level >200 c/mL following initial
             suppression;

          -  Documentation that the subject is negative for the human leukocyte antigen (HLA)
             B*5701 allele;

        Exclusion Criteria:

        Exclusionary Medical Conditions

          -  Women who are breastfeeding;

          -  Any evidence of an active (Centers for Disease Control and Prevention [CDC] Category
             C) disease. Exceptions include cutaneous Kaposi's sarcoma not requiring systemic
             therapy and historic CD4+ cell counts of <200 cells/cubic millimeter (mm).

          -  Subjects with any degree of hepatic impairment;

          -  Subjects positive for hepatitis B virus surface antigen (+HBsAg) at Screening or with
             an anticipated need for hepatitis C virus (HCV) therapy during the study;

          -  History or presence of allergy to the study drugs or their components or drugs of
             their class;

          -  Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or
             resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial
             neoplasia; other localized malignancies require agreement between the investigator and
             the study medical monitor for inclusion of the subject;

          -  Subjects who, in the investigator's judgment, pose a significant suicidality risk.
             Recent history of suicidal behavior and/or suicidal ideation may be considered as
             evidence of serious suicide risk;

        Exclusionary Treatments Prior to Screening or Day 1

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;

          -  Treatment with any of the following agents within 28 days of Screening: radiation
             therapy, cytotoxic chemotherapeutic agents, any immunomodulators that alter immune
             responses;

          -  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 drug;

          -  A history of use of only mono or dual NRTI therapy prior to starting cART;

          -  Use of etravirine at time of switch;

          -  Use of DTG at time of switch;

          -  Subjects receiving any prohibited medication listed in the protocol and who are
             unwilling or unable to switch to an alternate medication

        Exclusionary Laboratory Values or Clinical Assessments at Screening

          -  Evidence of primary viral resistance based on the presence of any
             resistance-associated major PI or any NRTI, NNRTI, or INI mutation in any prior
             resistance genotype assay result;

          -  Any verified Grade 4 laboratory abnormality, with the exception of Grade 4
             triglyceride abnormalities. A single repeat test is allowed during the screening
             period to verify a result;

          -  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;

          -  Alanine aminotransferase (ALT) >=5 times the upper limit of normal (ULN), or ALT >=3 ×
             ULN and bilirubin >=1.5 × ULN (with >35% direct bilirubin);

          -  Subject has CrCl of <50 mL/min using Modification of Diet in Renal Disease (MDRD);

          -  QTc (Bazett) >=450 msec or QTc (Bazett) >=480 msec for subjects with bundle branch
             block. The QTc is the QT interval corrected for heart rate according to Bazett's
             formula (QTcB). The QTc should be based on a single QTc value electrocardiogram (ECG)
             obtained.

          -  Eligibility of subjects for study participation will be decided by the investigators
             after taking into consideration various country specific guidelines, and
             notwithstanding the above mentioned minimum inclusion and exclusion criteria.