HIV/AIDS, Tuberculosis
Conditions
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.
Interventions
OTHERSame-Day Treatment
Treatment with ART or TB medication on day of HIV diagnosis
OTHERStandard treatment
Standard treatment
Sponsors
Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
Weill Medical College of Cornell University
Florida International University
University of California, Davis
Analysis Group, Inc.
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomized in a 1:1 ratio to standard or same-day treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention in care with viral suppression | 48 weeks after HIV testing | Proportion of participants who are in care with HIV-1 RNA \<200 copies/ml |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean treatment cost per participant | 48 weeks after HIV testing | Mean treatment cost per participant |
| Viral suppression | 48 weeks after HIV testing | Proportion of participants with HIV-1 RNA \<50 copies/ml and \<1000 copies/ml |
| Adherence by medication possession ratio | 48 weeks after HIV testing | Proportion of participants with 48-week adherence to ART of at least 90% by pharmacy refill records |
| Adherence by 3-day self-report | 48 weeks after HIV testing | Proportion of participants with perfect (100%) adherence as measured by 3-day self-report at 48 weeks after HIV testing |
| Treatment failure | 48 weeks | Proportion of participants meeting WHO criteria for ART failure and proportion initiating second-line ART during the study period |
| TB testing characteristics | These diagnostic tests will be conducted during the first week of study enrollment | 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 |
| Time in clinic | First study day and first study month | Median time spent in clinic during first day and month of the study |
| Coping with HIV diagnosis | 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing | Scores on the COPE survey |
| Mortality | 48 weeks after HIV testing | All-cause mortality |
| TB diagnosis after ART initiation | 48-week study period | Diagnosis of culture-positive TB after ART initiation (BACTEC MGIT 960, Becton Dickinson) |
| Incidence of immune reconstitution inflammatory syndrome (IRIS) | 48-week study period | Incidence of paradoxical or unmasking IRIS |
| Adverse events | 48-week study period | New Division of AIDS Grade 3 or Grade 4 signs, symptoms, or laboratory abnormalities that are at least a one-grade increase from baseline |
| Measure of hope and optimism | 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing | Scores on the State Hope Scale |
| Patient satisfaction | 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing | Scores on the HRSA Patient Satisfaction Survey |
| Time to death | 48-week study period | Days to death |
| Last missed dose of medication | 2 Weeks, 12 Weeks, 24 Weeks, 48 Weeks | Proportion of participants who report last missed dose of ART was at least 2 weeks ago |
| Connectedness to Treatment Setting | 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing | Scores on the Connectedness to Treatment Setting Scale |
Countries
Haiti
Outcome results
None listed