Optimizing reversal of HIV latency with combination therapy (pyrimethamine, lenalidomide, panobinostat)

Laborértékek

• A potential subject who meets any of the following criteria will be excluded from participation in this study: • Previous exposure to any of the studied LRAs in the last year • Acute or chronic co-infection with hepatitis B and/or C by the presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA in blood. • Co-medication with clinically significant interactions with LRA (see chapter 15.h for list) • Comorbidities affected by LRA compounds, such as but not limited to: known Glucose-6-phospate-dehydrogenase (G6PD) deficiency with anaemia, untreated haemolysis of any cause or hereditary thrombophilia not currently treated by anticoagulation. • Prolonged Qtc time >480ms at screening, as measured by electrocardiogram (ECG). • Patients of childbearing potential unless double contraceptive measures are taken. Non-childbearing is defined by one of the following criteria: amenorrhoea for ≥ 1 year, premature ovarian failure, assigned male at birth, or having undergone previous bilateral salpingo-oophorectomy, or hysterectomy • Sexual active patients unwilling to abstain from sex unless willing to use condom protection during and until 1 week after administration of study medication. • Active malignancy during the past year with the exception of basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi’s sarcoma treated with ARTalone or other indolent malignancies. • Registered allergies for any of the investigational medical products • Any lab abnormalities at screening as listed below: • Moderate kidney impairment, def ined as eGFR <50 mL/min. In PLWH on dolutegravir- or bictegravir-based ART regimens, cystatin C-based eGFR can be used, as creatinine-based eGFR is underestimat ed due to drug interf erence 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, serum sodium <130 mmol/L, serum potassium <3.0 mmol/L, serum phosphate <0.5 mmol/L, serum calcium <1.9 mmol/L, serum magnesium <0.5 mmol/L.

• Documented HIV-1 infection by 4th generation ELISA, Western Blot or PCR. • ≥ 18 years old. • World Health Organization (WHO) performance status 0 or 1. • Current plasma HIV RNA <50 copies/ml measured on the last 2 occasions, with measurements being at least 3 months apart. • Uninterrupted prescribed ART for a minimum of two consecutive years. • Considered >95% adherent to ART by treating physician. • 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. • Confirmed HIV subtype B. People with a high likelihood of subtype B can participate if they live in a HIV subtype B endemic region with HIV acquired there and in whom no HIV sequencing is available or can be done on stored samples. • People should be considered capable mentally and somatically by their treating physician to understand the informed consent procedure and undergo the study treatment.