Clinical trial to evaluate Metformin compared with placebo for reversal of accelerated aging in persons living with HIV 50 years or older

Prior treatment

• Participants previously diagnosed with diabetes mellitus, prediabetes and body mass index > 30 kg/m2.
• Any comorbidities or treatment with experimental drugs that according to the investigator could bias study results or entail additional risks for the participant.
• Participants with chronic hepatitis B and/or active hepatitis C or concurrent active or progressive liver disease.
• Participants unable to swallow study medication tablets during the treatment period.
• Participants receiving other medications that according to study drug label are contraindicated with metformin.

Other illness

• Participants with history of any of the following comorbidities: stroke, heart failure, dementia, myocardial infarction and cancer or history of lactic acidosis.
• Participants with decreased tissue perfusion or hemodynamic instability due to infection or other causes
• Participants with hypersensitivity or intolerance to any of the components of the study interventions as determined by the investigator.

Lab values

• Liver laboratory abnormalities: alanine aminotransferase (ALT) over 5 times the upper limit of normal (ULN) or ALT over 3xULN and bilirubin over 1.5xULN or any verified Grade 4 laboratory abnormality that to the investigators criteria would affect the safety of the participant if included in the study.

Other

• Impaired renal function (estimated glomerular filtration rate <60 mL/min).
• Pregnant or breastfeeding women, women wishing to conceive or unwilling to commit to contraceptive methods.
• Participants with active alcohol abuse: a. For men, heavy drinking is typically defined as consuming 15 drinks or more per week. b. For women, heavy drinking is typically defined as consuming 8 drinks or more per week.
• Participants that are unwilling to abstain from participating in another interventional clinical trial during the study follow up.

• Participant must be 50 years old or older, at the time of signing the informed consent.
• Participants with HIV-1 infection and an uninterrupted ART regimen in the 3 months prior to study entry a. Only switch for tolerability/convenience/access reasons to generic drugs or switch from ritonavir to cobicistat would be allowed in the 3-month window and as long as the components of the regimen are unchanged.
• HIV viral load (VL) <50 copies/mL at screening and in the year prior to study entry. a. A blip (50-200 copies/ml) would be allowed within 12 months prior to inclusion in the study, if preceded and followed by an undetectable VL determination.
• CD4 count > 500 cel/μL at screening.
• Participants with normal vitamin B12 levels at screening
• Participants with normal HOMA-IR (≤ 2.6)
• Body mass index (BMI) less than 30 Kg/m2.
• Female participants with suspected or documented menopause a. Peri- or post-menopausal, defined as having no menstrual periods for at least 12 months prior to study entry, or skipping at least one menstrual period in the 12 months prior to study entry. Peri- or post-menopausal status will be determined for candidates who have had the uterus removed by an assessment of blood follicle stimulating hormone
• Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.