HIV-associated cryptococcal meningitis Infections and Infestations
Conditions
Interventions
A nested randomised strategy trial to evaluate the safety and feasibility of two strategies for the delivery of TB preventive therapy (TPT) in HIV-associated cryptococcal meningitis: inpatient initiat
Sponsors
London School of Hygiene & Tropical Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: HIV-positive adults (aged =18 years) with HIV-associated cryptococcal meningitis (CSF CrAg positive)
Exclusion criteria
Exclusion criteria: 1. Active TB disease (as evidenced by any positive TB screening test or taking TB therapy at time of screening) 2. Jaundice 3. Abnormal liver function tests (bilirubin >3.5 mg/dl or ALT >200 IU/L) 4. Active hepatitis B infection (defined as hepatitis B surface antigen positive) 5. Known chronic liver disease 6. A clinical syndrome which in the opinion of the attending clinician, puts the patient at significant risk if he/she were to participate in the 1HP trial 7. Pregnant 8. Breastfeeding 9. Hypersensitivity to rifamycins or isoniazid 10. Contraindicated medication(s) (e.g. protease inhibitor)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| TB-disease free 1HP treatment completion at 18 weeks (after cryptococcal meningitis diagnosis and commencement of anti-fungal therapy). Treatment completion is defined as participant-reported adherence to >90% of the study medications for the duration of the trial. TB disease-free at 18 weeks is defined as (1) not receiving a diagnosis of active TB disease for the duration of the trial and (2) a negative WHO TB symptom screen at trial completion. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. 1HP treatment completion (defined as participant-reported adherence to >90% of the study medications) at 18 weeks 2. 1HP discontinuation of the study drugs for =5 consecutive days for any reason, measured using participant interviews and pill counts at 18 weeks 3. Incidence of grade 3-4 adverse events and serious adverse events (SAEs), measured using clinical and laboratory review at 18 weeks 4. Incidence of drug-induced liver injury defined as elevation of blood transaminase (ALT) alone =5x ULN (or ALT =3x ULN if bilirubin abnormal) or alkaline phosphatase (ALP) alone =2x ULN, measured at 18 weeks 5. Incident active TB (defined as clinician diagnosed TB based upon clinical syndrome and/or radiological evidence and/or mycobacteriological evidence), measured at 18 weeks 6. Survival measured using clinical review at 18 weeks 7. Fluconazole, rifapentine and dolutegravir concentrations measured using liquid chromatography-tandem mass spectrometry on days 5 and 14 of 1HP (for n=20 participants) | — |
Countries
Uganda
Outcome results
None listed