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MethodsAI467003 was a Phase 2b, randomised, active-controlled, blinded-to-BMS-986001 dose trial.HIV-1-infected adults with plasma HIV-1 RNA greater than 5000 copies per mL and CD4+ T-cell counts greater than 200 cells/mm 3 were randomised 2:2:2:3 to three BMS-986001 arms (100, 200 or 400 mg once daily), or reference arm (TDF 300 mg once daily), each with efavirenz (600 mg once daily) and lamivudine (300 mg once daily). Both subjects and investigators remained blinded to BMS-986001 dose, but not allocation, through Week 48. Proportion of subjects with plasma HIV-1 RNA less than 50 copies per mL and safety (serious adverse events [SAEs] and AEs leading to discontinuation) through Week 24 were primary endpoints. Resistance analysis was a secondary endpoint, and additional safety parameters were exploratory endpoints.AI467003 is registered with ClinicalTrials.gov (NCT01489046). FindingsA total of 757 subjects were assessed for eligibility and 301 randomised. Randomised subjects were assigned to receive either BMS-986001 (n=67 for the 100 mg once-daily group, n=67 for the 200 mg once-daily group, n=66 for the 400 mg once-daily group) or TDF (n=101 In a Phase 2a, dose-escalating, monotherapy study conducted for 10 days in treatment-experienced, HIV-1-infected, subjects who were not exposed to any antiretroviral treatment in the previous 3months, BMS-986001 demonstrated a median decrease in HIV-1 RNA from baseline of at least 1 log10 copies per mL for all doses. 19 These findings were used to support the design of this dosefinding Phase 2b study, which assessed the efficacy and safety of three doses of BMS-986001 (100, 200, and 400 mg once daily) versus tenofovir disoproxil fumarate (TDF 300 mg once daily), when coadministered with efavirenz (EFV 600 mg once daily) and lamivudine (3TC 300 mg once daily) in treatment-naïve, HIV-1-infected subjects. A detailed assessment of bone, renal, metabolic and mitochondrial parameters was performed to assess the safety of BMS-986001. 6 METHODS Study designAI467003 was a Phase 2b, randomised, active-controlled, blinded-to-BMS-986001 dose trial carried out at 47 sites across South America, North America, South Africa, Australia, Asia, and Europe.This study was conducted in accordance with Good Clinical Practice (GCP), as defined by the ParticipantsEligible subjects were treatment-naïve (defined as no current or previous exposure to an antiretroviral drug for more than 1 week), HIV-1-infected adults aged at least 18 years with plasma HIV-1 RNA greater than 5,000 copies per mL and CD4+ T-cell counts greater than 200 cells/mm 3 at screening.Exclusion criteria included a history of phenotypic and/or genotypic drug resistance testing showing resistance to EFV, TDF, or 3TC, presence of hepatitis B surface antigen, hepatitis C virus antibody or RNA, history of abnormal liver transaminases (defined as greater than three times the upper limit of normal) at screening, and creatinine clearance less than 60 mL/min at screening. All subjects provided written informed consent in agreement wi...