Clinical trial NCT03154320: A Trial of Same-Day Testing and Treatment to Improve Outcomes Among Symptomatic Patients Newly Diagnosed With HIV
Official title: A Trial of Same-Day Testing and Treatment to Improve Outcomes Among Symptomatic Patients Newly Diagnosed With HIV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV/AIDS
Tuberculosis
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
name: Weill Medical College of Cornell University
name: Florida International University
name: University of California, Davis
name: Analysis Group, Inc.
First posted: 2017-05-16
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized in a 1:1 ratio to standard or same-day treatment
Primary purpose: TREATMENT

Brief summary: This is a randomized, unblinded study comparing standard vs. same-day treatment for patients with TB symptoms (cough, fever, night sweats, or weight loss) at HIV diagnosis. Six hundred patients will be randomized in a 1:1 ratio to the standard group or the same-day treatment group. All study activities will take place at the GHESKIO Centers in Port-au-Prince, Haiti. The study population includes HIV-infected men and women ≥18 years of age who are ART-naïve, and who present with symptoms of TB (cough, fever, nights sweats, or weight loss) at HIV diagnosis.

Detailed description: This study is a randomized trial that will compare outcomes with standard and same-day treatment among patients with TB symptoms at HIV diagnosis. The standard group will receive same-day chest x-ray as well as Xpert Ultra testing with a spot specimen (with 48-hour turn-around-time). Participants will return for Xpert Ultra results and early morning sputum testing on Day 2. TB treatment will be provided on the day of diagnosis (Day 0 for those with high clinical and radiographic suspicion of TB, and Day 2 for those diagnosed by spot Xpert Ultra). Standard group participants who are not diagnosed with TB will be tested and treated for other opportunistic infections (OIs), as clinically indicated, and will initiate ART on Day 7. The same-day group will receive Xpert Ultra testing (with same-day results) and chest x-ray with same-day ART or TB treatment (on Day 0) based on test results. They will also be tested and treated for other OIs as clinically indicated. They will provide early morning sputum for repeat testing on Day 1. Both groups will receive Xpert Ultra testing on both spot and early morning specimens, with liquid culture on both specimens as the diagnostic gold standard; those with TB will start ART according to WHO guidelines.

Three specific aims are proposed:

Aim 1: To compare the proportion of participants in each group who are alive and in care with undetectable viral load (\<200 copies/ml) at 48 weeks after HIV testing. Hypothesis: The proportion of participants retained in care with undetectable viral load will be 51% in the standard and 65% in the same-day group.

Aim 2: To compare mortality in each group at 48 weeks after HIV testing. Hypothesis: Mortality will be 10% in the standard group and 4% in the same-day group.

Aim 3: To conduct a comparison of cost and cost-effectiveness of standard and same-day care, where cost is measured by the mean treatment cost and effectiveness is measured by being alive and in care with plasma HIV-1 RNA level \<200 copies/ml at 48 weeks after HIV testing. Hypothesis: Same-day treatment will cost less per patient retained in care with undetectable viral load.

Aim 4: To determine the rates of ART and TB treatment initiation, TB diagnosis after ART initiation, IRIS, adverse events, and adherence in both groups, and to evaluate the sensitivity, specificity, and predictive values of single tests and different testing combinations compared to liquid mycobacterial culture results.

Eligibility criteria: Inclusion Criteria:

* Men and women of ≥18 years of age
* Presence of cough, fever, night sweats or weight loss
* Ability and willingness to give written informed consent
* Documentation of positive HIV status (test conducted at GHESKIO)
* Acceptance of HIV diagnosis, defined as affirmative responses to two questions: "I believe that HIV and AIDS exist" and "I believe that the results of my HIV test show that I am infected".

Exclusion Criteria:

* Any use of ART in the past
* Treatment for TB in the year prior to screening visit
* Pregnancy or breastfeeding at the screening visit
* Active drug, alcohol use, or mental condition that would interfere with the ability to adhere to study requirements, in the opinion of the study physician
* Score of \<3 for any of the 7 questions on the ART readiness survey
* Planning to transfer care to another clinic during the study period
* Symptoms consistent with WHO stage 4 neurologic disease (cryptococcal meningitis, TB meningitis; central nervous system toxoplasmosis; HIV encephalopathy; progressive multifocal leukoencephalopathy)
* Severe illness, classified as one of the WHO "danger signs" of temperature \>39 degrees Celsius, pulse \>120 beats/minutes, respiratory rate \>30, or inability to walk unaided.

Primary outcomes:
measure: Retention in care with viral suppression
timeFrame: 48 weeks after HIV testing
Secondary outcomes:
measure: Mortality
timeFrame: 48 weeks after HIV testing
measure: Mean treatment cost per participant
timeFrame: 48 weeks after HIV testing
measure: Viral suppression
timeFrame: 48 weeks after HIV testing
measure: Adherence by medication possession ratio
timeFrame: 48 weeks after HIV testing
measure: Adherence by 3-day self-report
timeFrame: 48 weeks after HIV testing
measure: Treatment failure
timeFrame: 48 weeks
measure: TB testing characteristics
timeFrame: These diagnostic tests will be conducted during the first week of study enrollment
measure: Time in clinic
timeFrame: First study day and first study month
measure: Coping with HIV diagnosis
timeFrame: 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
measure: Connectedness to Treatment Setting
timeFrame: 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
measure: TB diagnosis after ART initiation
timeFrame: 48-week study period
measure: Incidence of immune reconstitution inflammatory syndrome (IRIS)
timeFrame: 48-week study period
measure: Adverse events
timeFrame: 48-week study period
measure: Measure of hope and optimism
timeFrame: 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
measure: Patient satisfaction
timeFrame: 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
measure: Time to death
timeFrame: 48-week study period
measure: Last missed dose of medication
timeFrame: 2 Weeks, 12 Weeks, 24 Weeks, 48 Weeks
Other outcomes:
Locations:
city: Port-au-Prince
country: Haiti
facility: GHESKIO
Study officials:
affiliation: Brigham and Women's Hospital
name: Serena P Koenig, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N, Schumacher SG, Ochodo EA, Haraka F, Zwerling AA, Pai M, Steingart KR, Horne DJ. Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis. Cochrane Database Syst Rev. 2021 Feb 22;2(2):CD009593. doi: 10.1002/14651858.CD009593.pub5.