Clinical trial NCT05085171: An Enhanced Package of Care to Reduce Reduce Mortality in Advanced HIV Disease
Official title: A Community-based Phase III, Cluster Randomized Trial of Point-of-care CD4 Testing and Enhanced Screening and Prophylaxis in Advanced HIV Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV Disease
Lead sponsor: Makerere University
Sponsor class: OTHER
Collaborators: name: University of Minnesota
First posted: 2021-10-20
Enrollment: 2400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: A community randomised controlled trial of 24 clinics,12 in the intervention arm and 12 in standard of care arm. Two levels of randomization planned
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: 24-week survival with retention in care
timeFrame: 24 weeks
Secondary outcomes:
measure: Evaluate sensitivity and specificity of the different TB point of care tests.
timeFrame: 24 weeks
measure: Incidence of OIs and associated hospitalization and mortality
timeFrame: Six months
measure: Tolerability and adherence to prophylaxis regimen and associated grade 3 to 5 adverse events
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: kisugu health center IV
Study officials:
References: