Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1U01AI068636 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From study entry to week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Probability of Death by Week 24 | The Kaplan-Meier estimate of cumulative probability of death by week 24 | From study entry to week 24 |
| Cumulative Probability of First AIDS Progression by Week 96 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mina C Hosseinipour, MD | University of North Carolina Lilongwe CRS | Study Chair |
| Johnstone Kumwenda, MBChB, FRCP | College of Med. JHU CRS | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS | Rio de Janeiro | 21045-900 | Brazil | |||
| Les Centres GHESKIO CRS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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 | ||
| Background | 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 | ||
| Background | 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 | ||
| 31761933 |
| Label | URL |
|---|---|
| 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) | View source |
Not provided
851 were randomized 1:1 to treatment strategies A and B. Results reported for 850 eligible participants; 1 was subsequently found ineligible and excluded from all analyses.
Recruited at AIDS Clinical Trials Units in 10 international countries. Recruitment occurred between October 31, 2011 (date of first participant was randomized) and June 9, 2014 (date of last participant was randomized).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Empiric | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Efavirenz | Drug | Participants will take one 600 mg tablet administered orally once daily without food. |
|
|
| Truvada | Drug | 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 FDC | Drug | 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 FDC | Drug | 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. |
|
| Isoniazid | Drug | INH 300 mg orally once daily |
|
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
| 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. | 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. | At weeks 0, 4, 24, and 48 |
| CD4+ T-cell Count | The absolute levels of CD4+ T-cell counts (cells/mm^3) | 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. | Weeks 0, 4, 24 and 48 |
| Time to Initiation of TB Treatment by Week 96 | Median time to TB treatment initiation since study entry | 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 | 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). | 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 | 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. | 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 | 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 | 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 | 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. | From study entry to week 48 |
| Port-au-Prince |
| 6110 |
| Haiti |
| GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS | Port-au-Prince | Haiti |
| YRG CARE Medical Ctr., VHS Chennai CRS | Rajiv Gandhi Salai Taramani | Chennai | 600113 | India |
| BJ Medical College CRS | Pune | Maharashtra | 411001 | India |
| AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS | Eldoret | 30100 | Kenya |
| Walter Reed Project - Kenya Med. Research Institute Kericho CRS | Kericho | 20200 | Kenya |
| College of Med. JHU CRS (30301) | Blantyre | Malawi |
| University of North Carolina Lilongwe CRS (12001) | Lilongwe | Malawi |
| San Miguel CRS | San Miguel | Lima region | Peru |
| Barranco CRS (11301) | Lima | 18 PE | Peru |
| Wits HIV CRS | Johannesburg | Gauteng | South Africa |
| CAPRISA eThekwini CRS | Durban | KwaZulu-Natal | 4011 | South Africa |
| Durban Adult HIV CRS | Durban | KwaZulu-Natal | South Africa |
| Soweto ACTG CRS (12301) | Johannesburg | South Africa |
| Joint Clinical Research Centre (JCRC) (12401) | Kampala | Uganda |
| Kalingalinga Clinic CRS (12801) | Lusaka | Zambia |
| UZ-Parirenyatwa CRS | AIDS Research Unit P.O. Box A178 | Harare | Zimbabwe |
| Derived |
| 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. |
| 27025337 | Derived | Hosseinipour 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. |
| Manual for Expedited Reporting of Adverse Events to DAID, Version 2.0, January 2010 | View source |
| FG001 | Arm B: IPT | 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). |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Intent to treat: All eligible participants were included in the baseline characteristics.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Empiric | 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 |
| BG001 | Arm B: IPT | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| HIV-1 RNA | Median | Inter-Quartile Range | log10 copies/mL |
| |||||||||||||||
| CD4+ T-cell count | Median | Inter-Quartile Range | cells/mm^3 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | 95% Confidence Interval | Cumulative probability per 100 persons | From study entry to week 24 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cumulative Probability of Death by Week 24 | The Kaplan-Meier estimate of cumulative probability of death by week 24 | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | 95% Confidence Interval | Cumulative probability per 100 persons | From study entry to week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | 95% Confidence Interval | Cumulative probability per 100 persons | From study entry to week 96 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | 95% Confidence Interval | Cumulative probability per 100 persons | From study entry to week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants With HIV-1 RNA Level <400 Copies/mL | Proportion of participants with HIV-1 RNA level <400 copies/mL. | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment. Missing data were assumed missing completed at random. | Posted | Number | 95% Confidence Interval | Proportion of participants | At weeks 0, 4, 24, and 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | CD4+ T-cell Count | The absolute levels of CD4+ T-cell counts (cells/mm^3) | Intent to treat: All eligible participants were included in the analysis: Participants were analyzed per original assigned randomized treatment. Missing data were assigned missing completely at random. | Posted | Median | Inter-Quartile Range | cells/ mm^3 | At weeks 0, 4, 24, and 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Intention to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment. Missing data were assumed missing completely at random. | Posted | Median | Inter-Quartile Range | cells/ mm^3 | Weeks 0, 4, 24 and 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Initiation of TB Treatment by Week 96 | Median time to TB treatment initiation since study entry | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Median | Inter-Quartile Range | Days | From study entry to week 96 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants With TB Diagnosis by Week 96 | Proportion of participants with TB diagnosis per current ACTG Diagnosis Appendix 60 by week 96 | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | Proportion of participants | From study entry to week 96 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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). | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | Proportion of participants | From study entry to week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | Proportion of participants | From study entry to week 48. The lab events were collected at study entry, weeks 2, 4, 8, 12, 16, 20, 24, and 48. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | Proportion of participants | From study entry to week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants With Reportable Hospitalization by Week 48 | Proportion of participants with reportable hospitalization reported by Week 48 | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | Proportion of participants | From study entry to week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | Proportion of participants | From study entry to week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants Who Prematurely Discontinued Antiretroviral Therapy by Week 48 | Proportion of participants with premature discontinuation of antiretroviral therapy (ART) by Week 48 | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment | Posted | Number | Proportion of participants | From study entry to week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Intent to treat: All eligible participants were included in the analysis: participants were analyzed per original assigned randomized treatment. | Posted | Number | 95% Confidence Interval | Cumulative probability per 100 persons | From study entry to week 48 |
|
From treatment dispensation to up to week 96
The protocol required reporting of signs and symptoms and laboratory abnormalities of >=Grade 2 and all grades of fever. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Empiric | 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 | 36 | 424 | 85 | 424 | 380 | 424 |
| EG001 | Arm B: IPT | 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). | 44 | 426 | 94 | 426 | 379 | 426 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Faecaloma | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Multi-organ failure | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hepatitis acute | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hepatitis alcoholic | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hepatotoxicity | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Immune reconstitution inflammatory syndrome | Immune system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Acquired immunodeficiency syndrome | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Central nervous system infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Cerebral toxoplasmosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Cytomegalovirus chorioretinitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea infectious | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Disseminated tuberculosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Furuncle | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| HIV infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Histoplasmosis disseminated | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Immune reconstitution inflammatory syndrome associated tuberculosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Lymph node tuberculosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Malaria | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Meningitis bacterial | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Meningitis cryptococcal | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Meningitis tuberculous | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Meningitis viral | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Neurosyphilis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Oesophageal candidiasis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Periorbital cellulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Salmonella sepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Subcutaneous abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Tuberculoma of central nervous system | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Tuberculosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Typhoid fever | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Viral vasculitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Anogenital warts | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Hairy cell leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Kaposi's sarcoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Ischaemic cerebral infarction | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Acute psychosis | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Reactive psychosis | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Uterine prolapse | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abortion induced | Surgical and medical procedures | MedDRA 23.1 | Systematic Assessment |
| |
| Cryptococcal fungaemia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| HIV-associated neurocognitive disorder | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Brain neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Non-Hodgkin's lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood bicarbonate decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vaginal discharge | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Oropharyngeal plaque | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood sodium increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ACTG Clinicaltrials.gov Coordinator | ACTG Network Coordinating Center, Social & Scientific Systems, Inc. | (301) 628-3313 | ACTGCT.Gov@s-3.com |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068257 | Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination |
| C098320 | efavirenz |
| D000069480 | Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination |
| D012293 | Rifampin |
| D007538 | Isoniazid |
| ID | Term |
|---|---|
| D000068698 | Tenofovir |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000068679 | Emtricitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D006834 | Hydrazines |
| D007539 | Isonicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D011725 | Pyridines |
Not provided
Not provided
| Male |
|
| Hispanic (Regardless of Race) |
|
| Asian, Pacific Islander |
|
| Malawi |
|
| Brazil |
|
| South Africa |
|
| Zimbabwe |
|
| Uganda |
|
| Zambia |
|
| Kenya |
|
| Peru |
|
| India |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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). |
|
|
|
|
|
|
|
|
|
|
|
|