PLUTO

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• A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Prior exposure to any of the studied LRAs in the previous 90 days 33 of 69 Based on CCMO protocol template CTR Version 3.0, May 2023 2026-525211-14-00, 1.3 (30-01-2026) CONFIDENTIAL 2. HIV-2 (double)infection 3. Co-infection with hepatitis B, unless resolved HBV (anti-HBc positive, anti-HBs positive and HBsAg negative) OR HBsAg positive and on continuous HBV-active antiviral therapy for ≥24 weeks prior to dosing, and HBV DNA undetectable or ≤ 200 IU/mL on two measurements (screening and within 4 weeks prior to enrolment), and no history of advanced fibrosis/cirrhosis (stage F2 and higher) 4. Co-infection with hepatitis C, measured by the presence of hepatitis C virus RNA in blood. 5. Co-medication with clinically significant interactions with LRA. 6. mRNA vaccine or adjuvant vaccine (e.g. Shingrix) in the previous 4 weeks. 7. Megaloblastic anaemia due to folate deficiency and untreated haemolysis of any cause 8. Active malignancy during the past year with the exception of basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi’s sarcoma treated with ART alone or other indolent malignancies. 9. History of suicide attempt or suicidal ideation. 10. History of ophthalmological medical problems leading to glaucoma or visual field disturbances (e.g. macula oedema). Refraction abnormalities that can be corrected by lenses are acceptable. 11. History of any medical condition with a causal relationship with hyperammonaemia. 12. History of epileptic seizures in the previous year. 13. Registered allergies for any of the investigational medical products 14. Sexually active participants who do not fit any of the following: a) Female subject of childbearing potential willing to comply with pregnancy tests before start and four weeks after end of treatment and willing to use of double contraceptive measures during and until 1 week after administration of study medication. Non-childbearing is defined by one of the following criteria: amenorrhoea for ≥ 1 year, premature ovarian failure, assigned male at birth, or having undergone bilateral salpingo-oophorectomy, or hysterectomy. b) Sexually active male PLWH who have sex with female partners of childbearing potential and willing to abstain from sex or willing to use condom protection during and until 1 week after administration of study medication. c) Sexually active male PLWH who have sex with postmenopausal female partners and willing to abstain from sex or willing to use condom protection or with a postmenopausal female partner on pre-exposure prophylaxis during and until 1 week after administration of study medication. d) Male PLWH who have sex with male partners and willing to abstain from sex or willing to use a condom protection during and until 1 week after administration of study medication. e) Male PLWH who have sex with male partners on preexposure prophylaxis during and until 1 week after administration of study medication. 15. Any lab abnormalities at screening as listed below: a) Moderate kidney impairment, defined as eGFR <50 mL/min. In PLWH on dolutegravir- or bictegravir-based ART regimens, cystatin C-based eGFR can be used, since possible drug interference with tubular creatinine excretion which leads to eGFR underestimation. b) Moderate hepatic impairment, defined as bilirubin > 3 x upper limit of normal (ULN) or ALT > 3x ULN c) Inadequate blood counts, defined as: haemoglobin <6.5 mmol/L (males) or <6.0 mmol/L (females), Absolute neutrophil count <1000 cells/mm3, thrombocytes <100 x109/L, international standardized ratio >1.6, activated partial thromboplastin time >40 seconds