An Enhanced Package of Care to Reduce Reduce Mortality in Advanced HIV Disease

Phase 3

Recruiting

• Conditions: The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV Disease
• Interventions: Other: Enhanced care package

• Registration Number: NCT05085171
• Lead Sponsor: Makerere University

Brief Summary

A community-based Phase III, cluster randomized trial that seeks to determine the 24 week survival with retention in care of point of care CD4 testing with visitect and an enhanced package of screening and prophylaxis for opportunistic infections among patients with advanced HIV disease.

Detailed Description

The study will be carried out in a population of HIV-infected adults with advanced HIV disease (CD4 \<200 cells/µL) in Uganda. It will be a Randomized controlled trial, Phase III in Uganda over a duration of 5 years assessing 24 weeks survival with retention in care. @4 clinic will be randomized to either receive the enhanced package or standard of care.

Description of Intervention Arm

1. Point-of-care CD4 testing via Visitect (point of care semi Quantitaive CD4 LFA) lateral flow assay (LFA)

2. Enhanced package of opportunistic infection screening and prophylaxis for CD4\<200, including:

* FujiFilm SILVAMP TB LAM (FujiLAM)

* Isoniazid (INH) + rifapentine: 1 month of therapy for latent TB(Tuberculosis) infection

* Cryptococcal Antigen semi-quantitative (CrAg-SQ) LFA (Immy)

* Treatment for disseminated CNS cryptococcal infection if high blood CrAg titer (\>3+ CrAg SQ)

Description of Standard of Care Arm

1. CD4 testing by flow cytometry

2. WHO recommended package of OI screening and prophylaxis, including:

* Urine TB LAM

* INH ( isoniazid 6 months)

* CrAg LFA

* Fluconazole for asymptomatic CrAg+ o 800mg daily x 2 weeks, then 400mg daily x 8 weeks, then 200mg daily.

Problem statement: Current lab-based CD4 testing results in a delay to either start ART(Antiretroviral therapy) or a delay in screening persons with low CD4s for OIs. At present, prioritization has been on ART initiation without systematic OI screening. Those with subclinical OIs started on ART unmask their OIs, with hospitalization / deaths for OIs such as cryptococcosis and TB.

We hypothesize that with point of care CD4 testing, same-day OI screening can occur, yet not interrupt prompt ART initiation for those at low risk (FujiLAM and CrAg-SQ negative) of unmasking immune reconstitution syndrome.

We hypothesize that point-of-care CD4 testing will improve 6-month survival by reducing lag time in CD4 results, thereby facilitating ART initiation, retention-in-care, and OI screening and prophylaxis.

We hypothesize that enhanced screening with the point-of-care FujiLAM, CrAg-SQ LFA, with enhanced prophylaxis for TB (1 month of INH and rifapentine) and with treatment for disseminated CNS cryptococcal infection in those CrAg+ with high titers (\>3+) will improve 6-month survival compared to current WHO-recommended standard practice in persons with advanced HIV disease.

Study Timeline

• Study First Submitted: 2021-10-08
• Study First Submitted QC: 2021-10-08
• Study First Posted: 2021-10-20
• Study Start: 2022-05-04
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-09
• Last Update Posted: 2022-07-12
• Primary Completion: 2027-03-01
• Study Completion: 2027-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2400

Inclusion Criteria

• Age >18 years
• CD4<200 cells/µL
• Ability and willingness to give informed consent for the enhanced package of care arm.

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Exclusion Criteria

• Known virologic suppression (viral load <1000 copies/mL) within prior 3 months
• Cannot or unlikely to attend regular clinic visits

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
intervention(Enhanced package of care) Arm	Enhanced care package	The patients with advanced HIV disease that receive HIV care at the intervention clinics will receive the enhanced intervention package which will include: point of care CD4 testing with visitect, screening for TB and cryptococcal meningitis using Fujifilm LAM and semiquantitative crAg LFA respectively and pre-emptive treatment with isoniazid and rifapentine for one month. Those with a high crAg titers will receive treatment for CNS cryptococcal disease.

Primary Outcome Measures

Name	Time	Method
24-week survival with retention in care	24 weeks	Comparison will be made between study arms of those who receive POC CD4 testing vs. those who receive standard flow cytometry, and those who receive the enhanced package of OI screening and prophylaxis, vs. those who receive the current WHO standard.

Secondary Outcome Measures

Name	Time	Method
Evaluate sensitivity and specificity of the different TB point of care tests.	24 weeks	After a positive FujiFilm TB LAM test, incidence of Xpert-positive or culture positive TB, and clinical outcomes to distinguish between false positive vs. true positive urine tests
Incidence of OIs and associated hospitalization and mortality	Six months	Incidence of active TB within 6 months, Incidence of cryptococcal meningitis and associated mortality.
Tolerability and adherence to prophylaxis regimen and associated grade 3 to 5 adverse events	24 weeks	percentage completion of regimen and proportions that get grade 3 and above AEs.

Trial Locations

Locations (1)

kisugu health center IV; 🇺🇬 Kampala, Uganda