Human Immunodeficiency Virus (HIV) Infection
Conditions
Keywords
Tuberculosis (TB) infection, Acquired immunodeficiency syndrome, Antiretroviral therapy (ART), Immune reconstitution inflammatory syndrome, People living with HIV (PLHIV), Same-day initiation (SDI) of ART, TB preventive treatment, Sub-Saharan African countries, HIV/TB-coinfection, immune reconstitution inflammatory syndrome (IRIS)
Brief summary
SaDAPT is a pragmatic, randomized, therapeutic-use trial comparing two approaches (ART first versus TB results first) for the timing of ART initiation in PLHIV with presumptive TB, but no signs of central nervous system (CNS) disease, in a routine primary and secondary care setting in southern Africa with regard to HIV viral suppression (VL \<400 copies/mL) 26 weeks after enrolment.
Detailed description
In this randomized controlled trial (RCT) two different, guideline-approved algorithms for antiretroviral therapy (ART) initiation in people living with HIV (PLHIV) with presumptive Tuberculosis (TB), but no signs of central nervous system (CNS) disease will be compared. In one arm, same-day initiation (SDI) of ART will be applied (ART first) for all participants independent of the status or results of initial TB investigations. In the other arm, an approach with deferral of ART initiation until TB is excluded or confirmed and TB treatment initiated will be applied (TB results first). The direct comparison of the two approaches in a pragmatic, two-country RCT conducted in a representative high-prevalence setting will provide evidence on the open question of optimal timing of ART initiation in the large subgroup of PLHIV with presumptive TB outside the CNS.
Interventions
OTHERART first- Therapeutic use trial
ART initiation on the day of enrolment independent of TB investigations in PLHIV with presumptive TB but no signs of CNS disease. The trial uses treatments and drug-doses as per international and national guidelines. All treatment components will be applied at standard dosage and no new substances or alternative indications will be tested.
OTHERTB results first- Therapeutic use trial
Deferral of ART initiation until active TB has been refuted or confirmed. PLHIV presenting with symptoms (cough, fever, night sweat, weight loss) are defined as presumptive TB, and should have microbiological TB investigations. Routine TB investigations in Malawi and Lesotho usually consist of two sputum bottles for analysis using nucleic acid amplification tests (Xpert MTB/RIF (Ultra)).The trial uses treatments and drug-doses as per international and national guidelines. All treatment components will be applied at standard dosage and no new substances or alternative indications will be tested.
Sponsors
Swiss National Science Foundation
SolidarMed
Kamuzu University of Health Sciences, Malawi
Swiss Tropical & Public Health Institute
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
London School of Hygiene and Tropical Medicine
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, parallel, open-label, 1:1 individually randomized, non-inferiority trial
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 12 years or older * HIV-positive * Not taking ART (naïve or reported no ART intake since 90 days or more) * Presenting with one or more TB symptoms according to W4SS * Unknown TB status * Planning to continue care at the study facility for at least 30 weeks * Willing and able to consent (age 18 years or older) or assent with guardian consent (age 12 to 17 years)
Exclusion criteria
* Medical condition requiring admission or referral to a higher level health facility at enrolment * Symptoms or clinical signs suggestive for diseases of the CNS * Positive cryptococcal antigen test (CrAg) * Reporting to be pregnant * Taking TB treatment, TB preventive therapy (TPT) or treatment against cryptococcal meningitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HIV viral suppression <400 copies/mL | 26 (22 - 40) weeks after enrolment | HIV viral suppression \<400 copies/mL (obtained from routine laboratory reports at study facility, from laboratory reports of referral facility in case of transfer out, or from dried blood spot (DBS) sample for participants without documented clinic visit but found during home visit tracing) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-traumatic mortality | during the first 30 weeks after enrolment | Non-traumatic mortality |
| Serious adverse events (SAEs) | during the first 30 weeks after enrolment | SAEs |
| Retention in care | 26 (22 - 30) weeks after enrolment | Retention in care, defined as a documented ART clinic visit between 22 and 30 weeks after enrolment |
| Engagement in care | 26 (22 - 30) weeks after enrolment | Engagement in care, defined as reporting regular ART intake, irrespective if a documented visit took place between 22 and 30 weeks after enrolment |
| Lost to follow-up | 26 (22 - 30) weeks after enrolment | Lost to follow-up, defined as non-retained in care and not reached through tracing |
| TB-Immune reconstitution inflammatory syndrome (IRIS) | during the first 30 weeks after enrolment | TB-Immune reconstitution inflammatory syndrome (IRIS) is defined as Adverse event of special interest (AESIs): AESIs |
| Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis) | during the first 30 weeks after enrolment | Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis), defined as any TB diagnosis after enrolment not classified as prevalent TB at enrolment |
| HIV viral suppression | at 26 (22 - 40) weeks | HIV viral suppression using different thresholds (\<20 copies/mL; \<100 copies/mL; \<1000 copies/mL) |
| Disengagement from care | 26 (22 - 30) weeks after enrolment | Disengagement from care, defined as non-engaged in care but reached through patient tracing |
Other
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of active TB diagnosed at enrolment (exploratory endpoint) | up to a maximum of 28 days after enrolment | Prevalence of active TB, defined as TB diagnosed clinically or microbiologically through the TB investigations at enrolment |
Countries
Lesotho, Malawi
Outcome results
None listed