a study to determine safety and efficacy of dolutegravir/abacavir/lamivudine (dtg/abc/3tc) in human immunodeficiency virus (hiv)-1 infected antiretroviral therapy (art) naïve women (aria)

Conditions: Infection, Human Immunodeficiency Virus; HIV Infections

Summary: this study is designed to demonstrate the non-inferior antiviral activity of dtg/abc/3tc fixed dose combination (fdc) once daily (od) compared to atazanavir plus ritonavir (atv+rtv) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (tdf/ftc fdc) od in hiv-1 infected, art-naïve women over 48 weeks. this study will also characterize the safety and tolerability of dtg/abc/3tc fdc compared to atv+rtv+tdf/ftc fdc. sufficient number of subjects will be screened in order to ensure a total of approximately 474 subjects will be randomized (237 in each study arm)


Eligibility criteria:
inclusion criteria: * hiv-1 infected females (gender at birth) \>=18 years of age * women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol) * hiv-1 infection as documented by screening plasma hiv-1 rna \>=500 c/ml. * documentation that the subject is negative for the hla-b\*5701 allele. * antiretroviral-naïve (\<=10 days of prior therapy with any antiretroviral agent following a diagnosis of hiv-1 infection). * signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening. exclusion criteria: * women who are pregnant or breastfeeding * women who plan to become pregnant during the first 48 weeks of the study * any subject who has had a medical intervention for gender reassignment * any evidence of an active centers for disease control and prevention (cdc) category c disease * subjects with any degree of hepatic impairment * subjects positive for hepatitis b at screening, or anticipated need for 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 * poses a significant suicidality risk * history of osteoporosis with fracture or requiring pharmacologic therapy * 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; * treatment with any agent, with documented activity against hiv-1 in vitro within 28 days of first dose of investigational product (ip) * 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 ip * any evidence of primary viral resistance based on the presence of any major resistance-associated mutation in the screening result or, if known, any historical resistance test result * any verified grade 4 laboratory abnormality, with the exception of grade 4 lipid abnormalities (total cholesterol, triglycerides, high density lipoprotein (hdl) cholesterol, low density lipoprotein (ldl) cholesterol) * 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 ≥ 3xuln and bilirubin ≥ 1.5xuln (with \>35% direct bilirubin) * subject has crcl of \<50 ml/min via cockroft-gault method * corrected qt interval (qtc (bazett)) ≥450msec or qtc (bazett) ≥480msec for subjects with bundle branch block.

Keywords: antiretroviral therapy naïve women once daily hiv infection atazanavir tenofovir/emtricitabine dolutegravir/abacavir/lamivudine fixed dose combination integrase inhibitor ritonavir