The Effect of Dolutegravir on Whole-body Insulin Sensitivity, Lipid and Endocrine Profile in Healthy Volunteers

Inclusion Criteria

• Willing and able to provide informed consent
• Cis-Male and Cis-Female healthy subjects without underlying conditions
• Subjects must have documented negative HIV serology by ELISA and P24 antigen and not receiving anti-HIV pre-exposure prophylaxis (PreP)
• Subjects must be clinically well volunteers aged between 18 to 60 years with BMI 18 kg/m2
• Healthy, as determined by the investigator or medically qualified designee based on a medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation (including ECG)
• Non-fasting blood glucose, total cholesterol and triglycerides within normal limits
• Subjects should have complete blood count (FBC) with normal differential and platelet count (detail below of specified normal range, table 1)

Table 1 - Compete FBC with normal differential & platelets count ranges Test Male Normal Range Female Normal Range Haemoglobin (g/L) 130-168 114-150 White blood cell count (x109/L) 4.2-10.6 4.2-11.2 Neutrophil count (x109/L) 2.0 - 7.1 Lymphocyte count (x109/L) 1.1 - 3.6 Monocyte count (x109/L) 0.2 - 0.9 Eosinophil count (x109/L) 0.0 - 0.5 Basophil count (x109/L) 0.0 - 0.2

• A female, may be eligible to enter and participate in the study if she:
• is of non-child-bearing potential defined as either 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,
• is of child-bearing 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 penile-vaginal intercourse. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the participant;
• Any intrauterine device with published data showing that the expected failure rate is 0.97 or BMI > 30kg/m2 and BMI 42 mmol/mol will be excluded.
• History or presence of allergy to the dolutegravir
• ALT or AST greater than or equal to 1.5 x Upper Limit of Normal (ULN) and total bilirubin greater than or equal to 1.5 x ULN excluded;
• Pregnancy and breastfeeding women
• Alcohol consumption >10 units/week
• Clinically relevant drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study.
• Unable to refrain from the use of prescription (e.g., dofetilide) or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives prior to the baseline visit and throughout the study until the follow-up period, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise participant safety.
• This includes on-going therapy with any of the following
• Metabolically active medications
• Any lipid-lowering medication
• Any testosterones treatments or supplements - Glucocorticoids including inhaled steroids except for 'as necessary' use
• Beta-blockers
• Thiazide diuretics and indapamide
• Thyroid preparations
• Psychotropic agents
• Anabolic steroids
• Megestrol acetate
• Dofetilide (or pilsicainide)