HIV InfectionPhase 4REMEMBERNCT01380080
REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment
A Phase 4 study testing Atripla (r), Efavirenz and Truvada in people with HIV Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 18 sites in 10 countries.
Trial summary
People with HIV have a high chance of becoming infected with TB, especially when they live in areas where TB infection is common. It can be difficult to diagnose TB in people who need to start HIV treatment right away. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Atripla (r), Efavirenz and Truvada
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 851 participants
- Where
- 18 sitesin 10 countries
- Study dates
- Oct 2011to Apr 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HIV-1 infection
- Willingness to start efavirenz-based ART as soon as possible and within no more than 3 days following randomization.
- CD4+ cell count <50 cells/mm^3 obtained within 45 days prior to study entry
- Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and total bilirubin ≤ 2.5 X ULN within 30 days prior to study entry.
- Creatinine clearance ≥30 mL/min either measured or estimated using values obtained within 30 days prior to study entry.
- Results from a hepatitis B surface antigen test performed within 30 days prior to study entry.
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- Agreement not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
- Female candidates of reproductive potential must have a negative serum or urine (15-25 mIU/mL) pregnancy test result within 7 days prior to study entry.
- Female candidates of reproductive potential who are participating in sexual activity that could lead to pregnancy must use two reliable methods of contraception while on study.
- Karnofsky performance score >/= 30 at time of study entry.
- Ability to swallow medications.
- Ability and willingness of participant or legal guardian/representative to provide informed consent.
- Intention to remain in the same general geographic region for the duration of study participation.
Who cannot join
- Presence of any confirmed or probable TB based on criteria listed in the current ACTG diagnosis appendix within 30 days prior to study entry and following completion of study-specific screening algorithm.
- Use of single-dose NVP for prevention of mother-to-child transmission (pMTCT) within 24 months prior to study entry.
- Use of prohibited medications within 30 days prior to study entry.
- Known allergy/sensitivity or any hypersensitivity to components of study-required ART or TB treatment.
- Current receipt of treatment for active TB or receipt of >14 days cumulative treatment for active TB within 96 weeks prior to study entry.
- Receipt of >30 days cumulative of INH prophylaxis within 48 weeks prior to study entry.
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- Receipt at any time prior to study entry of >7 days cumulative treatment with any ARV or combination of ARVs (except for ARVs taken for any length of time during pregnancy for pMTCT, or ARVs taken for occupational exposure).
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Current Grade ≥2 neuropathy.
- History of multi-drug-resistant (MDR) TB.
- Within 12 weeks prior to entry, exposure to a household member or co-worker with known MDR TB.
Trial locations and contacts
18 sites in 10 countries.
18 sites in 10 countries
South Africa4 sites
CAPRISA eThekwini CRS
Durban, KwaZulu-Natal, 4011
Durban Adult HIV CRS
Durban, KwaZulu-Natal
Wits HIV CRS
Johannesburg, Gauteng
Soweto ACTG CRS (12301)
Johannesburg
Haiti2 sites
Les Centres GHESKIO CRS
Port-au-Prince, 6110
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
Port-au-Prince
India2 sites
BJ Medical College CRS
Pune, Maharashtra, 411001
YRG CARE Medical Ctr., VHS Chennai CRS
Rajiv Gandhi Salai Taramani, Chennai, 600113
Kenya2 sites
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS
Eldoret, 30100
Walter Reed Project - Kenya Med. Research Institute Kericho CRS
Kericho, 20200
Malawi2 sites
College of Med. JHU CRS (30301)
Blantyre
University of North Carolina Lilongwe CRS (12001)
Lilongwe
Peru2 sites
Barranco CRS (11301)
Lima, 18 PE
San Miguel CRS
San Miguel, Lima region
Brazil1 site
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, 21045-900
About this study
Official title: Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis Treatment Regimens (REMEMBER)
People with HIV have a high chance of becoming infected with TB, especially when they live in areas where TB infection is common. It can be difficult to diagnose TB in people who need to start HIV treatment right away. Within about 6 months after starting HIV treatment, some of these people can become very sick with TB and can even die from it.
This study was being done in people who were starting HIV treatment and who lived in areas where the TB infection rate is high. The purpose of this study was to test an experimental approach to TB treatment to see if it is better than the usual approach. The experimental approach was to start TB treatment at the same time as HIV treatment, even when TB infection had not been found. The usual approach was to start TB treatment only if TB infection was found.
Read more
In this study, half of the people started TB treatment at the same time as they started their HIV treatment. The other half started TB treatment only if TB infection was found.
The study also tested how safe and effective it was to start TB treatment at about the same time as HIV treatment even when TB infection had not been found. The study collected information about diet, whether (and when) people in the study became sicker or died, how well their HIV was controlled, how they were feeling, how they were taking their medications, whether it mattered where they lived or what kind of HIV and TB care was standard, how many people were diagnosed with TB while in the study, and how the cost of the two treatment options on a national level could be compared.
Read the detailed description
This was a randomized, open-label, phase IV strategy trial for participants from resource-limited settings (RLS) who presented with advanced HIV disease and no probable or confirmed tuberculosis (TB), and who were initiating antiretroviral treatment (ART).
Participants were randomized to one of two strategy arms: immediate, empiric TB treatment (Empiric arm) or local standard of care TB treatment (IPT arm).
Randomization was balanced by clinical trial unit and stratified according to CD4+ T cell count (<25 vs. ≥25 cells/mm^3) and presence of any of the following prognostic factors: reportable hospitalization within the past 30 days, BMI <18.5 kg/m^2, or anemia (hemoglobin <8 g/dl).
Participants were followed for 96 weeks. Participants attended study visits at screening, enrollment, and weeks 1, 2, 4, 8, 12, 16, 20, 24 and 48. Signs and symptoms, ART modifications, concomitant medications, and clinical events as defined by AIDS Clinical Trials Group (ACTG) Appendix 60 were collected at each visit. Blood was collected for CD4 and HIV-1 RNA at study entry, weeks 4, 24 and 48, and blood for safety laboratories (liver function, hematology, and renal function) was collected at all visits except week 1. A sputum sample was collected and stored at study entry. Phone contact was conducted at weeks 60, 72, 84 and 96 to obtain information about vital status, reportable hospitalization, TB status (including screening and follow-up), TB and HIV treatment modifications, and quality of life.
- Conditions
- HIV Infection
- Being tested
- Atripla (r), Efavirenz, Truvada, Rifampin/isoniazid/pyrazinamide/ethambutol FDC, Rifampin/isoniazid FDC
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atripla (r)Drug
Patients are administered one tablet of Efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (EFV/FTC/TDF, Atripla) to taken be taken orally once daily at bedtime without food.
EfavirenzDrug
Also called EFV
Participants will take one 600 mg tablet administered orally once daily without food.
TruvadaDrug
Participants will take one tablet of Emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF, Truvada) administered orally once daily with or without food.
Rifampin/isoniazid/pyrazinamide/ethambutol FDCDrug
Participants will be administered Rifampin/isoniazid/pyrazinamide/ethambutol FDC tablets orally, once daily; dose by weight as determined in Table 5.1-1 of the protocol, for the first 8 weeks.
Rifampin/isoniazid FDCDrug
Participants will be administered rifampin/isoniazid FDC tablets orally, once daily; dose by weight as determined in Table 5.1-1 in the protocol, for 16 weeks following the first 8 weeks.
IsoniazidDrug
INH 300 mg orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Empiric | Experimental | Study treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only Receives: Drug: Atripla (r); Drug: Efavirenz; Drug: Truvada; Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC; Drug: Rifampin/isoniazid FDC |
| Arm B: IPT | Experimental | Study treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH). Receives: Drug: Atripla (r); Drug: Efavirenz; Drug: Truvada; Drug: Isoniazid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Probability of Death or Unknown Vital Status by Week 24
The Kaplan-Meier estimate of the cumulative probability of death or unknown vital status by week 24.
The vital status was considered unknown at week 24 if a participant prematurely discontinued from the study before week 24 and no vital status was obtained at week 48.
Measured: From study entry to week 24
Secondary outcomes (15)
Cumulative Probability of Death by Week 24
The Kaplan-Meier estimate of cumulative probability of death by week 24
Measured: From study entry to week 24
Cumulative Probability of First AIDS Progression by Week 96
The Kaplan-Meier estimate of the cumulative probability of first AIDS progression which was defined as the identification of a new World Health Organization (WHO) stage 3 or 4 condition
Measured: From study entry to week 96
Cumulative Probability of Death or AIDS Progression by Week 24
The Kaplan-Meier estimate of the cumulative probability of death or AIDS progression by week 24. AIDS progression was defined as new WHO stage 3 or 4 conditions occurred after study entry.
Measured: From study entry to week 24
Proportion of Participants With HIV-1 RNA Level <400 Copies/mL
Proportion of participants with HIV-1 RNA level <400 copies/mL.
Measured: At weeks 0, 4, 24, and 48
CD4+ T-cell Count
The absolute levels of CD4+ T-cell counts (cells/mm^3)
Measured: At weeks 0, 4, 24, and 48
CD4+ T-cell Count Change From Baseline
Change was calculated as the CD4+ T-cell count at the later weeks (4, 24 and 48) minus the baseline (week 0) CD4+ T-cell count.
Measured: Weeks 0, 4, 24 and 48
Time to Initiation of TB Treatment by Week 96
Median time to TB treatment initiation since study entry
Measured: From study entry to week 96
Proportion of Participants With TB Diagnosis by Week 96
Proportion of participants with TB diagnosis per current ACTG Diagnosis Appendix 60 by week 96
Measured: From study entry to week 96
Proportion of Participants With at Least One New Grade 3 or 4 Adverse Event That is at Least a One-grade Increase From Baseline by Week 48
Proportion of participants with at least one new Grade 3 or 4 laboratory or sign or symptom that is at least a one-grade increase from baseline by Week 48. Grade 3=Severe, Grade 4=Life-Threatening according to DAIDS AE Grading Table (see references).
Measured: From study entry to week 48
Proportion of Participants With at Least One New Grade 3 or 4 Targeted Laboratory Value That is at Least a One-grade Increase From Baseline by Week 48
Proportion of participants with at least one new Grade 3 or 4 that is at least a one-grade increase from baseline for the following targeted laboratory values by Week 48
The targeted laboratory events include hemoglobin, serum creatinine, ALT and AST
Measured: From study entry to week 48. The lab events were collected at study entry, weeks 2, 4, 8, 12, 16, 20, 24, and 48.
Proportion of Participants With Immune Reconstitution Inflammatory Syndrome (IRIS) by Week 48
Proportion of participants with IRIS (using current ACTG definition Appendix 60, see References) by Week 48. IRIS in participants with TB and other opportunistic infections may occur shortly after the initiation of potent combination ART, particularly in participants with advanced HIV disease.
Measured: From study entry to week 48
Proportion of Participants With Reportable Hospitalization by Week 48
Proportion of participants with reportable hospitalization reported by Week 48
Measured: From study entry to week 48
Proportion of Participants Who Prematurely Discontinued Any Component of TB Treatment by Week 48
Proportion of participants with premature discontinuation of any component of TB treatment by Week 48
Measured: From study entry to week 48
Proportion of Participants Who Prematurely Discontinued Antiretroviral Therapy by Week 48
Proportion of participants with premature discontinuation of antiretroviral therapy (ART) by Week 48
Measured: From study entry to week 48
Cumulative Probability of Death or AIDS Progression by Week 48
The Kaplan-Meier estimate of the cumulative probability of death or AIDS progression by week 48. AIDS progression was defined as new WHO stage 3 or 4 conditions occurred after study entry.
Measured: From study entry to week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startOct 2011
- Primary completion31 Jan 2015
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 851 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Mina C Hosseinipour, MD, Study chair, University of North Carolina Lilongwe CRSJohnstone Kumwenda, MBChB, FRCP, Study chair, College of Med. JHU CRS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01380080
- Sponsor's protocol ID
- ACTG A5274
- Other IDs
- 1U01AI068636
- Acronym
- REMEMBER
- Status last verified
- Oct 2024
- First submitted
- 22 Jun 2011
- Last updated
- 15 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
M. Hosseinipour, G. Bisson, S., et al. Empiric TB therapy does not decrease early mortality compared to Isoniazid Preventive therapy in adults with advanced HIV initiating ART: Results of ACTG A5274 (REMEMBER study). Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment and prevention; July 19-22, 2015; Vancouver, Canada. Abstract A-729-0105-03495
Johnstone Kumwenda, Amita Gupta, et al. Empiric TB therapy versus IPT in HIV-infected persons initiating ART (ACTG A5274 48 week results). Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1383
Gregory P. Bisson, Amita Gupta, et al. Urine LAM Testing in Advanced HIV-Infected Adults in a Trial of Empiric TB Therapy. Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1650
Manabe YC, Andrade BB, Gupte N, Leong S, Kintali M, Matoga M, Riviere C, Samaneka W, Lama JR, Naidoo K, Zhao Y, Johnson WE, Ellner JJ, Hosseinipour MC, Bisson GP, Salgame P, Gupta A. A Parsimonious Host Inflammatory Biomarker Signature Predicts Incident Tuberculosis and Mortality in Advanced Human Immunodeficiency Virus. Clin Infect Dis. 2020 Dec 17;71(10):2645-2654. doi: 10.1093/cid/ciz1147.
PubMed 31761933Hosseinipour MC, Bisson GP, Miyahara S, Sun X, Moses A, Riviere C, Kirui FK, Badal-Faesen S, Lagat D, Nyirenda M, Naidoo K, Hakim J, Mugyenyi P, Henostroza G, Leger PD, Lama JR, Mohapi L, Alave J, Mave V, Veloso VG, Pillay S, Kumarasamy N, Bao J, Hogg E, Jones L, Zolopa A, Kumwenda J, Gupta A; Adult AIDS Clinical Trials Group A5274 (REMEMBER) Study Team. Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1198-209. doi: 10.1016/S0140-6736(16)00546-8.
PubMed 27025337
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis Treatment Regimens (REMEMBER)
- ClinicalTrials.gov ID
- NCT01380080
- Acronym / sponsor ID
- REMEMBER / ACTG A5274
- Conditions
- HIV Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 851 participants (actual)
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Oct 2011 (actual)
- Primary completion
- 31 Jan 2015 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 27 Jun 2011 (estimated)
- Results
- Posted 23 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People with HIV have a high chance of becoming infected with TB, especially when they live in areas where TB infection is common. It can be difficult to diagnose TB in people who need to start HIV treatment right away. Within about 6 months after starting HIV treatment, some of these people can become very sick with TB and can even die from it.
This study was being done in people who were starting HIV treatment and who lived in areas where the TB infection rate is high. The purpose of this study was to test an experimental approach to TB treatment to see if it is better than the usual approach. The experimental approach was to start TB treatment at the same time as HIV treatment, even when TB infection had not been found. The usual approach was to start TB treatment only if TB infection was found.
In this study, half of the people started TB treatment at the same time as they started their HIV treatment. The other half started TB treatment only if TB infection was found.
The study also tested how safe and effective it was to start TB treatment at about the same time as HIV treatment even when TB infection had not been found. The study collected information about diet, whether (and when) people in the study became sicker or died, how well their HIV was controlled, how they were feeling, how they were taking their medications, whether it mattered where they lived or what kind of HIV and TB care was standard, how many people were diagnosed with TB while in the study, and how the cost of the two treatment options on a national level could be compared.
Detailed description
This was a randomized, open-label, phase IV strategy trial for participants from resource-limited settings (RLS) who presented with advanced HIV disease and no probable or confirmed tuberculosis (TB), and who were initiating antiretroviral treatment (ART).
Participants were randomized to one of two strategy arms: immediate, empiric TB treatment (Empiric arm) or local standard of care TB treatment (IPT arm).
Randomization was balanced by clinical trial unit and stratified according to CD4+ T cell count (<25 vs. ≥25 cells/mm^3) and presence of any of the following prognostic factors: reportable hospitalization within the past 30 days, BMI <18.5 kg/m^2, or anemia (hemoglobin <8 g/dl).
Participants were followed for 96 weeks. Participants attended study visits at screening, enrollment, and weeks 1, 2, 4, 8, 12, 16, 20, 24 and 48. Signs and symptoms, ART modifications, concomitant medications, and clinical events as defined by AIDS Clinical Trials Group (ACTG) Appendix 60 were collected at each visit. Blood was collected for CD4 and HIV-1 RNA at study entry, weeks 4, 24 and 48, and blood for safety laboratories (liver function, hematology, and renal function) was collected at all visits except week 1. A sputum sample was collected and stored at study entry. Phone contact was conducted at weeks 60, 72, 84 and 96 to obtain information about vital status, reportable hospitalization, TB status (including screening and follow-up), TB and HIV treatment modifications, and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Empiric | Experimental | Drug: Atripla (r), Drug: Efavirenz, Drug: Truvada, Drug: Rifampin/isoniazid/pyrazinamide/ethambutol FDC, Drug: Rifampin/isoniazid FDCStudy treatment for Arm A participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral treatment as soon as possible following randomization and within no more than 3 days following randomization plus a 4-drug anti-tuberculosis treatment (ATT) regimen (defined as rifampin/isoniazid/ethambutol/pyrazinamide) as soon as possible following randomization and within no more than 7 days following initiation of antiretroviral therapy. After 2 months (or 8 weeks), the 4-drug ATT will be followed with 4 months (or 16 weeks) of 2-drug ATT (defined as rifampin/isoniazid). All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only |
| Arm B: IPT | Experimental | Drug: Atripla (r), Drug: Efavirenz, Drug: Truvada, Drug: IsoniazidStudy treatment for Arm B participants is the strategy of initiating study-provided or other FDA-approved or tentatively approved antiretroviral therapy as soon as possible following randomization and within no more than 3 days following randomization and of initiating anti-TB treatment (ATT) only when indicated according to local standard practice and at the discretion of the site investigator. All participants will be followed through week 96. Drug provision by or through the study will be through week 48 only. Pyridoxine is provided by the sites to all participants while they are receiving isoniazid (INH). |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- HIV-1 infection
- Willingness to start efavirenz-based ART as soon as possible and within no more than 3 days following randomization.
- CD4+ cell count <50 cells/mm^3 obtained within 45 days prior to study entry
- Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and total bilirubin ≤ 2.5 X ULN within 30 days prior to study entry.
- Creatinine clearance ≥30 mL/min either measured or estimated using values obtained within 30 days prior to study entry.
Key exclusion criteria (11 listed)
- Presence of any confirmed or probable TB based on criteria listed in the current ACTG diagnosis appendix within 30 days prior to study entry and following completion of study-specific screening algorithm.
- Use of single-dose NVP for prevention of mother-to-child transmission (pMTCT) within 24 months prior to study entry.
- Use of prohibited medications within 30 days prior to study entry.
- Known allergy/sensitivity or any hypersensitivity to components of study-required ART or TB treatment.
- Current receipt of treatment for active TB or receipt of >14 days cumulative treatment for active TB within 96 weeks prior to study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atripla (r)Patients are administered one tablet of Efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (EFV/FTC/TDF, Atripla) to taken be taken orally once daily at bedtime without food. | Drug | Arm A: Empiric, Arm B: IPT |
| EfavirenzAlso: EFVParticipants will take one 600 mg tablet administered orally once daily without food. | Drug | Arm A: Empiric, Arm B: IPT |
| TruvadaParticipants will take one tablet of Emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF, Truvada) administered orally once daily with or without food. | Drug | Arm A: Empiric, Arm B: IPT |
| Rifampin/isoniazid/pyrazinamide/ethambutol FDCParticipants will be administered Rifampin/isoniazid/pyrazinamide/ethambutol FDC tablets orally, once daily; dose by weight as determined in Table 5.1-1 of the protocol, for the first 8 weeks. | Drug | Arm A: Empiric |
| Rifampin/isoniazid FDCParticipants will be administered rifampin/isoniazid FDC tablets orally, once daily; dose by weight as determined in Table 5.1-1 in the protocol, for 16 weeks following the first 8 weeks. | Drug | Arm A: Empiric |
| IsoniazidINH 300 mg orally once daily | Drug | Arm B: IPT |
Primary outcome
Cumulative Probability of Death or Unknown Vital Status by Week 24
Time frame: From study entry to week 24
The Kaplan-Meier estimate of the cumulative probability of death or unknown vital status by week 24. The vital status was considered unknown at week 24 if a participant prematurely discontinued from the study before week 24 and no vital status was obtained at week 48.
15 secondary outcomes
Cumulative Probability of Death by Week 24
Time frame: From study entry to week 24
Cumulative Probability of First AIDS Progression by Week 96
Time frame: From study entry to week 96
Cumulative Probability of Death or AIDS Progression by Week 24
Time frame: From study entry to week 24
Proportion of Participants With HIV-1 RNA Level <400 Copies/mL
Time frame: At weeks 0, 4, 24, and 48
CD4+ T-cell Count
Time frame: At weeks 0, 4, 24, and 48
CD4+ T-cell Count Change From Baseline
Time frame: Weeks 0, 4, 24 and 48
Time to Initiation of TB Treatment by Week 96
Time frame: From study entry to week 96
Proportion of Participants With TB Diagnosis by Week 96
Time frame: From study entry to week 96
Proportion of Participants With at Least One New Grade 3 or 4 Adverse Event That is at Least a One-grade Increase From Baseline by Week 48
Time frame: From study entry to week 48
Proportion of Participants With at Least One New Grade 3 or 4 Targeted Laboratory Value That is at Least a One-grade Increase From Baseline by Week 48
Time frame: From study entry to week 48. The lab events were collected at study entry, weeks 2, 4, 8, 12, 16, 20, 24, and 48.
Proportion of Participants With Immune Reconstitution Inflammatory Syndrome (IRIS) by Week 48
Time frame: From study entry to week 48
Proportion of Participants With Reportable Hospitalization by Week 48
Time frame: From study entry to week 48
Proportion of Participants Who Prematurely Discontinued Any Component of TB Treatment by Week 48
Time frame: From study entry to week 48
Proportion of Participants Who Prematurely Discontinued Antiretroviral Therapy by Week 48
Time frame: From study entry to week 48
Cumulative Probability of Death or AIDS Progression by Week 48
Time frame: From study entry to week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundM. Hosseinipour, G. Bisson, S., et al. Empiric TB therapy does not decrease early mortality compared to Isoniazid Preventive therapy in adults with advanced HIV initiating ART: Results of ACTG A5274 (REMEMBER study). Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment and prevention; July 19-22, 2015; Vancouver, Canada. Abstract A-729-0105-03495
- BackgroundJohnstone Kumwenda, Amita Gupta, et al. Empiric TB therapy versus IPT in HIV-infected persons initiating ART (ACTG A5274 48 week results). Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1383
- BackgroundGregory P. Bisson, Amita Gupta, et al. Urine LAM Testing in Advanced HIV-Infected Adults in a Trial of Empiric TB Therapy. Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 16-1650
- Derived from this study: PubMed 31761933Manabe YC, Andrade BB, Gupte N, Leong S, Kintali M, Matoga M, Riviere C, Samaneka W, Lama JR, Naidoo K, Zhao Y, Johnson WE, Ellner JJ, Hosseinipour MC, Bisson GP, Salgame P, Gupta A. A Parsimonious Host Inflammatory Biomarker Signature Predicts Incident Tuberculosis and Mortality in Advanced Human Immunodeficiency Virus. Clin Infect Dis. 2020 Dec 17;71(10):2645-2654. doi: 10.1093/cid/ciz1147.
- Derived from this study: PubMed 27025337Hosseinipour MC, Bisson GP, Miyahara S, Sun X, Moses A, Riviere C, Kirui FK, Badal-Faesen S, Lagat D, Nyirenda M, Naidoo K, Hakim J, Mugyenyi P, Henostroza G, Leger PD, Lama JR, Mohapi L, Alave J, Mave V, Veloso VG, Pillay S, Kumarasamy N, Bao J, Hogg E, Jones L, Zolopa A, Kumwenda J, Gupta A; Adult AIDS Clinical Trials Group A5274 (REMEMBER) Study Team. Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1198-209. doi: 10.1016/S0140-6736(16)00546-8.
- The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)Link provided by the sponsor.
- Manual for Expedited Reporting of Adverse Events to DAID, Version 2.0, January 2010Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mina C Hosseinipour, MD study chair
University of North Carolina Lilongwe CRS
Johnstone Kumwenda, MBChB, FRCP study chair
College of Med. JHU CRS
18 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atripla (r), Efavirenz and Truvada in people with HIV Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 18 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in South Africa, Haiti, India, Kenya, Malawi and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative Probability of Death or Unknown Vital Status by Week 24 (time frame: From study entry to week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01380080, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.