A Trial of Same-Day Testing and Treatment to Improve Outcomes Among Symptomatic Patients Newly Diagnosed With HIV

Tuberculosis Clinical Trial

Official title:

A Trial of Same-Day Testing and Treatment to Improve Outcomes Among Symptomatic Patients Newly Diagnosed With HIV

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03154320
• Other study ID #: AI131998
• Status: Completed
• Phase: N/A
• Start date: November 6, 2017
• Est. completion date: April 16, 2021

Study information

• Verified date: September 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: April 16, 2021
• Est. primary completion date: April 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV/AIDS
• Tuberculosis

Intervention

Other:
• Same-Day Treatment
Treatment with ART or TB medication on day of HIV diagnosis
• Standard treatment
Standard treatment

Locations

Country	Name	City	State
Haiti	GHESKIO	Port-au-Prince

Sponsors (6)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Analysis Group, Inc., Florida International University, Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic, University of California, Davis, Weill Medical College of Cornell University

Country where clinical trial is conducted

Haiti, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Retention in care with viral suppression	Proportion of participants who are in care with HIV-1 RNA <200 copies/ml	48 weeks after HIV testing
Secondary	Mortality	All-cause mortality	48 weeks after HIV testing
Secondary	Mean treatment cost per participant	Mean treatment cost per participant	48 weeks after HIV testing
Secondary	Viral suppression	Proportion of participants with HIV-1 RNA <50 copies/ml and <1000 copies/ml	48 weeks after HIV testing
Secondary	Adherence by medication possession ratio	Proportion of participants with 48-week adherence to ART of at least 90% by pharmacy refill records	48 weeks after HIV testing
Secondary	Adherence by 3-day self-report	Proportion of participants with perfect (100%) adherence as measured by 3-day self-report at 48 weeks after HIV testing	48 weeks after HIV testing
Secondary	Treatment failure	Proportion of participants meeting WHO criteria for ART failure and proportion initiating second-line ART during the study period	48 weeks
Secondary	TB testing characteristics	Sensitivity, specificity, predictive values, and likelihood ratios of spot and early morning Xpert Ultra results and chest x-ray, as single and as combined tests, with liquid culture as gold standard	These diagnostic tests will be conducted during the first week of study enrollment
Secondary	Time in clinic	Median time spent in clinic during first day and month of the study	First study day and first study month
Secondary	Coping with HIV diagnosis	Scores on the COPE survey	2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
Secondary	Connectedness to Treatment Setting	Scores on the Connectedness to Treatment Setting Scale	2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
Secondary	TB diagnosis after ART initiation	Diagnosis of culture-positive TB after ART initiation (BACTEC MGIT 960, Becton Dickinson)	48-week study period
Secondary	Incidence of immune reconstitution inflammatory syndrome (IRIS)	Incidence of paradoxical or unmasking IRIS	48-week study period
Secondary	Adverse events	New Division of AIDS Grade 3 or Grade 4 signs, symptoms, or laboratory abnormalities that are at least a one-grade increase from baseline	48-week study period
Secondary	Measure of hope and optimism	Scores on the State Hope Scale	2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
Secondary	Patient satisfaction	Scores on the HRSA Patient Satisfaction Survey	12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing
Secondary	Time to death	Days to death	48-week study period
Secondary	Last missed dose of medication	Proportion of participants who report last missed dose of ART was at least 2 weeks ago	2 Weeks, 12 Weeks, 24 Weeks, 48 Weeks