Combining Latency Reversing Agents to Address the HIV Reservoir

Korábbi kezelés

• Prior exposure to any of the studied LRAs in the previous 90 days
• 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)
• Co-medication with clinically significant interactions with LRA
• mRNA vaccine or adjuvant vaccine (e.g. Shingrix) in the previous 8 weeks.
• 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.
• History of epileptic seizures in the previous year.

Más betegség

• HIV-2 (double)infection
• Co-infection with hepatitis C, measured by the presence of hepatitis C virus RNA in blood.
• History of suicide attempt or suicidal ideation.
• 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.
• History of any medical condition with a causal relationship with hyperammonemia.
• Registered allergies for any of the investigational medical products
• Sexually active participants who do not fit any of the following:
  • 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.
  • 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.
  • 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.
  • Male PLWH who have sex with male partners on preexposure prophylaxis during and until 1 week after administration of study medication.

Laborértékek

• Any lab abnormalities at screening as listed below:
  • 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.
  • Moderate hepatic impairment, defined as bilirubin > 3 x upper limit of normal (ULN) or ALT > 3x ULN
  • 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,

Egyéb

• Megaloblastic anaemia due to folate deficiency and untreated haemolysis of any cause

• Documented HIV-1 infection, confirmed by 4th generation ELISA, Western Blot or PCR.
• Age ≥ 18 years old.
• Confirmed HIV1, subtype A, B, C or D.
• Uninterrupted ART therapy for a minimum 6 months. .
• Plasma HIV RNA <≤50 copies/ml prior to inclusion at two consecutive measurements at least three months apart.
• No disclosed missed ART on more than 2 days per month.
• Current blood CD4+T-cell count of ≥200 cells/mm3
• No clinical signs of cellular immunodeficiency or AIDS.
• Pre-ART plasma HIV RNA ≥1000 copies/mL.
• Able to understand provided information and to give informed consent.