drug-drug interaction study of vesatolimod in adults with hiv-1 who have very low or undetectable virus levels

Conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection

Summary: the goal of this clinical study is to learn more about the impact of cobicistat (cobi) (p-glycoprotein (p-gp), breast cancer resistance protein (bcrp), and strong cytochrome p450 enzyme \[cyp\]3a inhibitor), voriconazole (vor) (strong cyp3a inhibitor), and rifabutin (rfb) (moderate cyp3a inducer) on the study drug, vesatolimod (ves), in people with hiv-1 on antiretroviral therapy (art).


Eligibility criteria:
key inclusion criteria: * on an antiretroviral therapy (art) regimen for at least 6 consecutive months, with no change in the art regimen within 2 months prior to screening. permitted arts are as follows: * cohort 1: a regimen of (bictegravir \[bic\], dolutegravir \[dtg\], raltegravir \[ral\], or doravirine \[dor\]) plus nucleoside reverse transcriptase inhibitors (nrtis). examples of acceptable regimens include bic/emtricitabine/tenofovir, dtg/ abacavir (abc)/3tc, dtg/3tc, dtg + emtricitabine/tenofovir, or dor/3tc/tenofovir * cohort 2: a dtg-based regimen is required (dtg/abc/3tc), (dtg/3tc), or (dtg + nrtis) * plasma hiv-1 rna levels less than 50 copies/ml at screening * have normal hematologic function with an absolute neutrophil count greater than or equal to 1.5 × 10\^9/l, platelets greater than or equal to 150 × 10\^9/l; hemoglobin greater than or equal to 10.5 g/dl for females and greater than or equal to 11.5 g/dl for males * clusters of differentiation (cd) 4 t cell count greater than or equal to 350 cells/μl * aspartate aminotransferase (ast) and alanine aminotransferase (alt) less than or equal to 2.5 x upper limit of normal (uln) and total bilirubin less than or equal to 1.5 mg/dl, or normal direct bilirubin and creatinine less than or equal to 1.25 x uln * have a calculated creatinine clearance (clcr) of at least 60 ml/min (using the cockcroft-gault method) based on serum creatinine and actual body weight as measured at screening and upon admission * individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception * must be willing and able to comply with all study requirements and available to complete the study schedule of assessments * in the judgment of the investigator, be in good general health, based on review of the results from a screening visit key exclusion criteria: * have received any study drug within 30 days prior to study dosing * participation in any other clinical study (including observation studies) without prior approval from the sponsor is prohibited while participating in this study * have current alcohol or substance abuse judged by the investigator to potentially interfere with individual compliance or individual safety, or a positive drug or alcohol test at screening or baseline * no evidence of chronic hepatitis b virus (hbv) infection (defined as positive hepatitis b surface antigen \[hbsag\] and/or positive hbv core antibody with positive reflex hbv dna polymerase chain reaction (pcr)). note: positive hbv core antibody with negative reflex hbv dna pcr results are acceptable * no evidence of active hepatitis c virus (hcv) infection (defined as positive hepatitis c antibody and hcv rna above lower limit of quantitation). note: positive anti-hcv antibody and negative hcv pcr results are acceptable * acute febrile illness within 35 days prior to day 1 * have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study * received any vaccine or immunomodulatory medication within 4 weeks prior to screening. elective vaccination (eg, flu shot, hepatitis a or b vaccine) during the course of the study will require prior approval from the sponsor * coronavirus disease of 2019 (covid-19) vaccinations are allowed, with the requirement that they should not be administered within 7 ± 2 days of receiving ves * have a history of any of the following: * significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria * significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity) * known hypersensitivity to the study drugs, their metabolites, or to formulation excipients * autoimmune disease * significant cardiac disease or a family history of long qt syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years * syncope, palpitations, or unexplained dizziness * implanted defibrillator or pacemaker * liver disease, including gilbert syndrome * severe peptic ulcer disease requiring prolonged (≥ 6 months) medical treatment * medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). a history of cholecystectomy is not exclusionary * have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with individual treatment, assessment, or compliance with the protocol * for cohort 1, individuals with cyp2c19 genotype of cyp2c19\*2/\*2, cyp2c19\*2/\*3, or cyp2c19\*3/\*3 note: other protocol defined inclusion/exclusion criteria may apply.