• A5404: SARS-CoV-2 Immune Responses after COVID-19 Therapy and Vaccine

    July 23, 2021 Alexis Sexton

    Right now there is no medicine proven to treat COVID-19 in people who are not sick enough to be hospitalized. Researchers will be testing different investigational medicines that they believe are most likely to help people with COVID-19.

    They want to see if these investigational medicines:

    • Are safe for those who need them
    • Can help people get better faster
    • Can get rid of the virus
    • Can help keep oxygen levels up
    • Can keep people from getting sicker
    • Can prevent people from having to go to the hospital

    The whole study lasts about 6 months (24 weeks).

    During the study you would have in-person visits with tests to check on your health. Most of these visits happen during the first month of the study.

    You would also have phone calls or videos chats with the researcher from your home.

    The study team will give you a diary to keep track of your temperature each evening and any symptoms you have. You’ll be asked to fill out this diary for the first 28 days.

    If the study is right for you, you will have your first visit, or entry visit, to meet with a researcher for tests and to be placed in a treatment group.

    Each study medicine will be compared to a placebo. A placebo looks like the real drug but doesn’t have any actual medicine in it. This gives researchers something to compare the study medicine to. You would not know if you are receiving the study medicine or placebo until the end of the study. If a standard treatment for COVID-19 is found during the study, that treatment will be used instead of placebo. Different medicines may be tested during the study at the same time. One type of investigational medicine you might receive is called a monoclonal antibody. Antibodies are naturally made by your body to help fight disease. Monoclonal antibodies are made in the lab and help your body attack invaders, such as viruses, to keep them from entering your cells. Once you are placed in a treatment group, you will receive more information on that investigational medicine being tested, including any possible side effects.

     

    To learn more about this study click here.

  • ACTG A5362: A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study

    June 17, 2021 Alexis Sexton

    Study Description
    A5362 is a study for people with pulmonary tuberculosis (TB) without evidence of resistance to the TB drugs isoniazid (INH) or rifampin (RIF). Participants will be enrolled in one of three treatment groups. Duration of treatment will vary depending on which treatment group the participant is enrolled, but all participants will be in the study for 65 weeks.

    Study Status:    Open to Accrual

    Why is this study being done?

    • To determine if taking a shorter 3-month regimen of a new combination of TB drugs is better than taking a 6-month regimen that is standard of care for the treatment of TB.
    • To look at the tolerability of the study drugs, the effect the drugs have on the electrical activity of the heart, and will measure the level of these drugs in blood.

    Who can join?

    People who:

    • Are 18 years of age or older
    • Have pulmonary TB with or without history of prior treatment, and without known resistance of INH or RIF
    • Have a normal chest X-ray at screening
    • For participants living with HIV: CD4 cell count ≥100 and taking or planning to take anti-HIV therapy
    • Not more than 5 days of treatment directed against active TB for the current TB episode

    What do I need to do in the study?

    For this three-arm study, participants will receive treatment in either:

    Arm 1

    Rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) high dose for 2 weeks; then PHZE + CFZ standard dose for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ standard dose 5 weeks, for a total of 13 weeks of study treatment.

    Arm 2 (Standard of Care)

    Rifampin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampin/isoniazid (RH) for 18 weeks, for a total of 26 weeks of study treatment.

    Arm C

    PHZE + CFZ standard dose for 4 weeks; switch to standard of care, completing RHZE for 4 weeks; then RH for 18 weeks.

    All participants will have blood samples taken to measure the amount of anti-TB drugs in the body, and pictures taken to look for changes in skin color. All participants will undergo routine safety monitoring.  Participants will be followed in the study for 65 weeks.

    What treatments or drugs are involved with this study?

    Study TB medications are provided by the study. Antiretroviral medications are not provided by the study.

  • A5386: N-803 with or without bNAbs for HIV-1 control in participants living with HIV-1 on suppressive ART

    May 26, 2021 Alexis Sexton

    Full Title: A Phase 1 Clinical Trial of the Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) with and without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

    Scientists are looking for ways to effectively clear HIV that rests in areas of the body where standard antiretroviral treatment (ART) is unable to reach. IL-15 superagonist (N-803) appears to reactivate HIV that is “asleep” and is also thought to increase the body’s natural immune response to HIV. Broadly neutralizing antibodies (bNAbs), such as 10-1074 and VRC07-523LS, have been shown to control growth of HIV in the blood and to increase the body’s immune response to HIV. N-803 alone or in combination with bNAbs may provide greater control of HIV than previous efforts.

    Purpose of this Study: This research study is trying to find out if N-803, VRC07-523LS, and 10-1074 are safe and effective at reactivating and targeting the latent cell pool of HIV RNA during an ATI (analytical treatment interruption). All participants will receive eight doses of N-803. Half of participants will also receive 10-1074 and VRC07-523LS. A year after starting study treatment, participants will stop ART for up to 24 weeks to see how well their immune systems control growth of HIV (analytic treatment interruption or ATI).  Participants will be followed closely to see if ART should be restarted. After restarting ART, participants will be followed for another 24 weeks.

    Major requirements for entering the study (things that must be true for you):

    • Living with HIV.
    • Have a low or undetectable viral load for at least 2 years.
    • Be willing to take a superagonist and broadly neutralizing antibodies and complete study related tests.
    • Agree to use contraception/birth control methods.
    • Be between 18 and 70 years old.
    • Be willing to temporarily stop taking antiretrovirals or ART.

    Events or conditions that would prevent you from participating (things that cannot be true about you):

    • Recent serious illness or condition requiring hospitalization.
    • Breastfeeding or pregnant.
    • Active Hepatitis B or C infection or history of AIDS-defining conditions.
    • Current CD4 cell count less than 500 or ever had a CD4 cell count less than 200.

    Talk to your study staff for a complete list of inclusion/exclusion criteria.

    Intervention:

    • Eight doses of N-803 given by needle under the skin; half of participants will receive two doses of 10-1074 and one dose of VRC07-523LS given intravenously (through a catheter in the vein).

    Procedures:

    • Blood and urine tests at scheduled clinic visits for safety evaluations and to check your immune function.
    • Leukapheresis (collection of immune cells through a catheter in the vein) (a procedure similar to donating platelets) will be completed twice.
    • Lymph node fine-needle aspirate (a type of biopsy using a needle) is an optional procedure which will be done prior to study entry and at Week 13.

    Duration of Study: Maximum of 2 years. Arm A will receive one dose of N-803 at Week 1 and then every 3 weeks for a total of eight doses. Arm B will receive one dose each of VRC07-523LS and 10-1074 at Step 1 entry, a dose of N-803 at Week 1 and then every 3 weeks for a total of eight doses, and a second dose of 10-1074 at Week 9. Follow-up visits will occur at Weeks 26, 32, 46 and 52. Week 52 also marks the beginning of the ATI, which can last up to 24 weeks of frequent visits. There will also be follow-up visits at 4, 12, and 24 weeks from the restart of ART.

  • A5391: Doravirine for Persons with Excessive Weight Gain on Integrase Inhibitors and Tenofovir Alafenamide (The Do IT Study)

    May 20, 2021 Alexis Sexton

    Weight gain after starting antiretroviral therapy (ART) is common, but recent studies have found that some people living with HIV (PLWH) who are taking an integrase strand transfer inhibitor (INSTI) combined with tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir alafenamide/lamivudine (TAF/3TC) may gain more weight than people taking other drug combinations. A rising number PLWH are overweight or obese. Higher BMI and weight gain on ART increase the risk for diabetes, heart disease and stroke. Researchers are looking to see if PLWH who have gained a significant amount of weight after starting or switching to an INSTI-containing regimen, can either reduce their rate of weight gain over time or even lose weight with a change to a different ART regimen. This study will include participants who are living with HIV-1, who have been virally suppressed for > 48 weeks on a regimen consisting of an INSTI and TAF/FTC or TAF/3TC and who have experienced > 10% weight gain since the initiation of this ART regimen.

    Purpose of this Study: This research study is trying to find out if PLWH who had > 10% weight gain after starting an antiretroviral therapy (ART) regimen that included an INSTI in combination with TAF/FTC (or TAF/3TC) could gain less weight, or maybe lose weight, after switching to an ART regimen containing doravirine (DOR) with either TAF/FTC (or TAF/3TC), or the related medication tenofovir disoproxil fumarate/emtricitabine (TDF/FTC [or TDF/3TC]). DOR is an FDA-approved antiretroviral drug for the treatment of HIV-1 and a member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) medication class. In multiple studies, DOR was shown to be just as effective as INSTI medications for treating HIV.

    Requirements to Enter Study (things that must be true for you):

    • Living with HIV-1.
    • Be ≥ 18 years old.
    • Currently on an Integrase Inhibitor (INSTI) containing regimen (BIC, DTG or RAL), with > 48 weeks INSTI+TAF/FTC (or TAF/3TC) dosing prior to study entry.
    • Have experienced > 10% weight gain in the 1-3 years after starting these medications.
    • Have a body mass index (BMI) >5 kg/m2.
    • Have study related tests done, including a DEXA Scan (X-Ray Scan measuring measure lean muscle, body fat and bone density).
    • Agree to use contraception/birth control methods if capable of becoming pregnant.
    • Be willing to change ART if randomized to Arms 1 or 2.

    Exclusion Criteria (things that cannot be true about you):

    • Recent serious illness or condition requiring hospitalization.
    • Breastfeeding or pregnant.
    • Historic or current evidence of resistance to the study medication or other medications in its class.
    • Plans to undergo weight loss surgery or to start significant changes to your diet or exercise habits

    Talk to your study staff for a complete list of inclusion/exclusion criteria.

    Intervention:

    When you enter this study, you will be randomized (assigned by chance, as if by roll of dice) to one of three study groups. Because the randomization is equal, you will have a 33% chance of being in any of the following study groups:

    1. Group 1: You will continue taking TAF/FTC (or TAF/3TC) but will stop your INSTI and take DOR; your ART will be DOR+TAF/FTC (or TAF/3TC) for 48 weeks.
    2. Group 2: You will stop your INSTI and TAF/FTC (or TAF/3TC) and will switch to DOR+TDF/FTC (or TDF/3TC) for 48 weeks.
    3. Group 3: You will continue your current ART of an INSTI+TAF/FTC (or TAF/3TC) for 48 weeks.

    Procedures:

    • Blood and urine tests at scheduled clinic visits for safety evaluations and other research testing.
    • Questionnaires asking for information on adherence to ART and diet and exercise habits.
    • DEXA Scan (Dual-Energy X-Ray Absorptiometry) to measure lean muscle, body fat and bone density.

    Duration of Study: Almost 1 year (48 weeks). Follow-up visits will occur at Weeks 4, 12, 24, 36 and 48 (study completion).

  • A5379: B-Enhancement of HBV vaccination in persons living with HIV (BEe-HIVe): Evaluation of HEPLISAV-B

    October 28, 2020 Alexis Sexton

    A5379 is a study looking at hepatitis B vaccination in adults living with HIV. Hepatitis B is a serious viral infection that affects the liver and is transmitted through blood and body fluids. The study will involve individuals who have received a previous hepatitis B vaccination but the vaccine did not respond well and individuals who have never received the vaccination. The study will take place both in the US and internationally. The study will compare how well an individual responds to the vaccine in different groups based on the type of vaccine and number of doses.

    Purpose of the Study: Vaccination for hepatitis B in individuals living with HIV does not always work, especially in those with impaired immune systems or ability to fight infection. Prevention of hepatitis B in individuals living with HIV has primarily been done by vaccinating with a series of 3 shots given over 6 months. A new vaccine, called HEPLISAV-B, has been approved that may provide a better response than what has currently been used. The researchers will study whether this vaccine will prove to be more effective than the current standard.

    Requirements to Enter Study:

    Living with HIV

    Been on HIV treatment for more than 56 days

    Previously received vaccines for hepatitis B, but the vaccines didn’t work

    There will be a small group of participants (73) who have never been vaccinated for hepatitis B.

    CD4 cell count (the number of white blood cells that fight infection) more than 100

    HIV viral load (how much HIV is in the body) less than 1000

    In the group vaccinated with a hepatitis B vaccine, the vaccination was over 168 days ago

    Exclusion: No previous hepatitis B infection or exposure to hepatitis B infection

    Treatment:  HEPLISAV-B vaccine given at entry and at 4 weeks or

    HEPLISAV-B vaccine given at entry, 4 weeks and 24 weeks or

    Engerix-B vaccine given at entry, 4 weeks and 24 weeks.

    Duration:  72 weeks

  • A5371: A Single-Arm, Open-Label, Pilot Study of Semaglutide for Non-Alcoholic Fatty Liver Disease (NAFLD), a Metabolic Syndrome with Insulin Resistance, Increased Hepatic Lipids, and Increased Cardiovascular Disease Risk (The SLIM LIVER Study)

    October 8, 2020 Alexis Sexton

    Short Title: The Slim Liver Study

    Brief Description: About 30-40% of people living with HIV have a condition called NAFLD, or non-alcoholic fatty liver disease.  NAFLD is caused by high levels of stored fat in the liver. Most people with NAFLD also have other complications like high cholesterol, obesity, increased belly fat or type 2 diabetes. These complications can lead to cardiovascular disease (any disease of the heart or blood vessels that can lead to a stroke or heart attack).  In fact, most of the health problems that are associated with NAFLD are related to these conditions of the heart or metabolism.  Without treatment, NAFLD can advance to more serious liver disease. By using a drug that can lower the level of stored fat in the liver, people living with HIV may be able to treat NAFLD and reduce their risk of cardiovascular disease and other complications.

    Purpose of this Study: The purpose of this study is to evaluate the safety and tolerability of a drug called semaglutide and to see if it can reduce the amount of fat stored in the liver.

    Requirements to Enter Study (things that must be true for you):

    • Living with HIV with 2 HIV viral loads less than 50 copies in the last year and a CD4 T-cell count of at least 200
    • On your current HIV medications for at least 24 weeks
    • Willingness to have MRI scans
    • Agree to use contraception/birth control methods (if needed)
    • Able to store semaglutide in a cool location
    • Be 18 years old or older
    • Be willing to sign the consent after discussion with the research staff
    • Be willing to give yourself an injection once a week

    Exclusion Criteria (things that cannot be true for you):

    • Hepatitis B or C Virus infection (not previously treated)
    • Any plans to change diet or exercise significantly during the study period
    • Breastfeeding, pregnancy, or plans to become pregnant while on study
    • Liver disease with cirrhosis
    • Current diabetes mellitus
    • Chronic pancreatitis
    • Prior gastric (stomach) surgery (lab band, gastric sleeve or gastric bypass surgery) or plans to undergo one of these surgeries in the near future
    • High alcohol use

    Treatment:

    • Semaglutide subcutaneous injection once weekly for 24 weeks.

    Procedures:

    • Blood tests at clinic visits
    • Stool collections
    • MRI scans
    • Adherence monitoring, physical function assessment, food diary, and questionnaires

    Duration of Study: Approximately 48 weeks

  • A5372: Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals (RPT-DTG PK Study)

    September 1, 2020 Alexis Sexton

    The purpose of this research study is see if taking medications to prevent tuberculosis (TB) affect the drug levels in blood of a commonly used HIV medication called dolutegravir (DTG) and if an extra dose of DTG is needed during this TB preventive treatment. The other medicines, rifapentine (RPT) and isoniazid (INH), are drugs used to prevent active TB in people who have been exposed to TB. This study will also help us make sure that people tolerate the medicines and that they are safe when given together. In many countries, DTG is the recommended first-line treatment for HIV. DTG, RPT, and INH are proven beneficial treatments for people living with HIV and latent TB, but it is unclear whether these treatments work differently when taken together. Understanding how DTG interacts with the short-term treatment for latent TB (1HP) is very important for delivering both treatments effectively.

    Purpose of the Study:  To see if taking a medicine to treat TB called RPT, affects the levels of DTG (an HIV medicine) in the blood or not.

    Requirements to Enter Study:  This study is for people living with HIV between the ages of 18-65 and who either tested positive for the bacteria that causes tuberculosis (TB) or live in a country where TB infection occurs frequently. Participants must be taking dolutegravir as part of a three drug regimen to treat HIV and must have a viral load < 50 copies/ml.  In addition to these criteria, blood samples will be drawn for lab tests to check general health.  Participants will also need to weigh at least 40 kilograms and have either a chest x-ray or CT scan of their lungs to check for active TB disease.

    Treatment:  Participants will continue ART medications that include DTG and 2 nucleoside reverse transcriptase inhibitors for the entire study period.

    TB medication to prevent active TB disease will begin at entry into the study and include the RPT and a second medication used to treat TB called isoniazid (INH) along with daily vitamin B6, to decrease the risk of side effects from INH.

    The study will have two (2) groups. Group 2 will only open after the results from Group 1 are reviewed.

    Below are the medicines that you will take during the study depending on which Group you are in:

    Group 1

    • DTG 50 mg orally twice daily – about 12 hours apart
      • 1st dose will be taken in the morning; this will not be supplied by the study
      • 2nd dose will be taken in the evening; this will be supplied by the study for 4 weeks
    • 1HP: INH 300 mg + RPT 600 mg orally once daily (in the morning) for 4 weeks (supplied by the study)

    Group 2 (upon opening)

    • DTG 50 mg orally once daily (in the morning) (not supplied by the study)
    • 1HP: INH 300 mg + RPT 600 mg orally once daily (in the morning) for 4 weeks (supplied by the study)

    You will continue taking your existing ART drugs while on the study – your ART must include 2 NRTIs (excluding TAF) during the study. Your ART will not be provided by the study.

    You will also receive pyridoxine (vitamin B6) 25 or 50 mg with each dose of INH based on the current local, national, or international dosing guidelines.

    Because the blood draws on study visits will be dependent on the time you take the drugs, you will need to take your HIV drugs and drugs provided by the study (except second dose of DTG if you are in Arm 1) in the morning during the duration of the study. If you generally take your HIV drugs in the evening, you will need to switch to taking them in the morning for this study, including at least 3 days before the Day 0 visit. On the study visit days, you will hold on taking the drugs until you arrive at the clinic.

    Duration of Study:  Most people will be on this study for six weeks (4 weeks on study treatment and two weeks of follow-up). You may be on study up to 11 weeks if you have to have additional follow-up visits to check your viral load. There are 7 or 8 scheduled visits during this time.

  • A5312: The Early Bactericidal Activity of High Dose or Standard Dose Isoniazid among adult Participants with Isoniazid-Resistant or Drug Sensitive Tuberculosis

    August 31, 2020 Alexis Sexton

    This study is for participants who have pulmonary tuberculosis (TB), a bacterial infection in their lungs. Isoniazid (INH) is a drug commonly used to treat TB. Sometimes, the bacteria that cause TB can become resistant to INH, and then INH does not work as well at fighting the bacteria. This study will treat people with INH-resistant TB with different doses of INH to see if INH can still fight the bacteria if we just increase the dose.

    Purpose

    We will compare how well the drug works at higher doses for participants who have resistant TB to how well the drug works at regular doses for participants who have TB that is sensitive to the drug. The study will also compare the safety and tolerability of the different doses of INH.

    Study Stages

    If you join this study, you will need to be admitted to the hospital for at least 9 days. If you have not stopped taking INH you may need to be admitted for longer (up to 16 days in total) so that there is time for the INH to wash out of your body. While you are in the hospital, you will be asked to collect the sputum that you cough up in a container. Seeing how many bacteria are in the sputum you cough up will help us to know how well the medicine is working. After you are discharged from the hospital, you will come to the clinic 14 days later for a final visit.

    If you meet the eligibility requirements for the study, you will have a test to see if you have INH-resistant TB, and if it is low-level or high-level resistance. (With low-level resistance, the bacteria are not as resistant to INH as they are with high-level resistance.) You may also be asked to provide sputum for other types of resistance tests.

    Depending on the test result, you will be assigned to one of 3 groups:

    • If you have low-level INH resistance, you will either be referred to receive standard TB treatment outside of the study or be randomized (like a flip of a coin) to receive 5, 10 or 15 mg/kg INH once a day for 7 days. Randomized means that you have equal chance of being in any of these 3 groups. (Mg/kg, or milligrams per kilogram, means the amount of INH in milligrams you will receive for each kilogram you weigh.)
    • If your test shows no INH resistance, you will either be referred to receive standard TB treatment outside the study or you will receive 5 mg/kg INH once a day for 7 days.
    • If you have high-level resistance, you will either be referred to received standard TB treatment outside the study or you will be randomized to receive 15 or 20 mg/kg INH once a day for 7 days.

    INH will be provided for you. In addition, you must also take vitamin B6 once a day while taking INH, to help prevent possible side effects of INH. Vitamin B6 will also be provided to you. When you are finished taking study drug, you will be referred for full TB treatment outside the study.

    Inclusion Criteria:

    • New or current pulmonary TB
    • Adults between the ages of 18 and 65

    Exclusion Criteria

    • Known exposure to extensively resistant TB (XDR-TB)

    Duration of Study: About 23 days

    Total number of participants: Between 128 and 218

  • A5401: ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies

    July 21, 2020 Alexis Sexton

    Study Description:

    A master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with COVID-19. It begins with a phase II evaluation, followed by a transition into a larger phase III evaluation for promising agents.

    Why is this study being done?

    To rapidly and efficiently evaluate multiple potential therapeutics for COVID-19 in an outpatient setting.

    Who can join?

    • Ambulatory Adult (18 years or older)
    • Active SARS-CoV-2 infection <7 days prior to Entry
    • At least one typical COVID-19 symptom for <10 days prior to Entry, plus one the following symptoms present within 48 hours of entry:

    –Fever or feeling feverish, cough, shortness of breath at rest or with activity, sore throat, body or muscle pain, fatigue, headache, chills

    • Tailored per study agent requirements

    Duration of study: 28 days of intensive follow-up, followed by limited follow-up through 24 weeks.

     

    To find more information click here and to see our press release relating to this study click here.

  • A5300B:Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Participants (PHOENIx)

    February 20, 2020 Alexis Sexton

    This trial is in household contacts (HHC) at high risk for developing multidrug resistant tuberculosis (MDR-TB) which is an infection that does not get better with standard treatment for TB.  HHC means any person that  lives with, has lived with, or shared housekeeping duties in a home or the same place with a person (an Index Case) who has pulmonary MDR-TB (a lung infection or pneumonia with TB) and started treatment for MDR-TB within the past 90 days. It is also for people who have spent more than 4 hours indoors with the index case, during the week before they started MDR-TB treatment.

    High-risk household contacts are those with HIV or an immune system problem not from HIV like cancer , latent TB infection (a history of TB infection in the past based on testing), and young children below the age of 5 years.

    Purpose of this Study: 

    Is to compare how safe and effective 26 weeks of Delamanid (DLM), a medicine used to treat TB,  is versus 26 weeks of isoniazid (INH), a standard medicine to treat or prevent TB,  for preventing infection with TB (latent TB) or confirmed or probable active infection with TB among participantshigh risk HHC (see above for description).

    Requirements to Enter Study:

    The Index Case must be an adult (18 years and older) with pulmonary MDR-TB who has started MDR-TB treatment within the past 90 days, who has one or more household contacts and gives site staff permission to call and visit the household contacts.

    The Household contact must be a High-Risk Contact:

    • Children up to 5 years of age regardless of standard tests for TB known as the tuberculin skin test (TST) or the interferon gamma release assay (IGRA), a blood test for TB, or HIV status.
    • Adults, adolescents, and children ≥5 years of age who are TST-positive (defined as a skin test bump ≥5 mm in size) and/or IGRA test-positive and whose HIV status is negative, indeterminate, or unknown and who are not immunosuppressed from another condition besides HIV.
    • Adults, adolescents, and children ≥5 years of age who are HIV-infected or are immunosuppressed without HIV (defined as receiving anti-tumor necrosis factor (TNF) treatment, or in chronic renal failure receiving dialysis, or being solid organ or hematologic transplant recipients), regardless of TST/IGRA

    Treatment:

    Household contacts will be randomly assigned (like a flip of a coin) one of two groups:

    Group A will receive:

    DLM daily for adults, adolescents, and children, given for 26 weeks

    Group B will receive:

    • INH daily for adults, adolescents, and children, given for 26 weeks
    • Pyridoxine (vitamin B6) daily for adults, adolescents, and children, given for 26 weeks

    All high-risk HHCs in the same HH will receive the same randomized regimen.

    Duration of Study:

    All participants will be in this study for 96 weeks.