• A5380: Glecaprevir/pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection (PURGE-C)

    February 19, 2020 Alexis Sexton

    This is a study to treat participants, with or without HIV, who are found to have been recently infected with the Hepatitis C virus (HCV). This known as acute HCV.

    Purpose of this Study: People who are recently infected with HCV are often considered to have acute HCV. People with acute HCV have a good chance of being cured of the infection when they are treated with a combination of two drugs within the first 6 months of being infected. This study is being done to see if a shorter course of treatment will be effective if started early in the infection (Step 1). In case of failure with this shorter course of treatment, a longer and different treatment for HCV will be offered (Step 2).

    Requirements to Enter Study:

    • Age ≥18 years of age
    • With or without HIV. If living with HIV, on a stable treatment (antiretroviral regimen) or untreated due to lack of treatment per physician.
    • HIV RNA <50 and CD4 >100 cells/ mm3 (CD4 cells are a kind of white blood cell that are a measure of the immune system)
    • May not have Hepatitis B or prior Hepatitis C
    • Recently infected with HCV
    • Cannot be pregnant or breastfeeding
    • Must be willing to use birth control to prevent pregnancy
    • Must be willing to come to study visits
    • Must be able to swallow pills
    • May not have other known liver disease

    Study Drugs: Glecaprevir/pibrentasvir (G/P) Fixed-dose Combination (FDC-single tablet) three pills by mouth once a day for 4 weeks (Step 1). If this medicine does not work for you after the 4 weeks or you become infected again while on study, you will be asked to take the G/P with or without Ribavirin for a longer time, 8-16 weeks longer.

    Duration of Study: Up to 28 weeks on Step 1 and up to an additional 40 weeks if on Step 2.

  • A5381: Observational Cohort to Assess Therapeutic Efficacy and Emergence of HIV Drug Resistance Following Initiation of Tenofovir-Lamivudine-Dolutegravir (TLD) for First- or Second-Line ART

    February 11, 2020 Alexis Sexton

    This is a study for people who have HIV and qualify to switch to or receive Dolutegravir containing antiretroviral therapy (ART, group of medicine used to treat HIV). Taking TLD (combination pill of three medicines for HIV, tenofovir-lamivudine-dolutegravir) has shown to be better tolerated, work better against the virus known as virologic efficacy, have fewer drug-drug interactions, and have less frequent onset of HIV drug resistance than Efavirenz containing ART. In August 2017, a decision was made to start using TLD for first- and second-line ART in many places in the world. This study is designed to help us understand the risks and benefits of TLD roll-out in low- and middle-income countries that may not use viral load testing and HIV resistance testing (a way to measure if a drug will work against your HIV) to guide ART management.  Each participant will be assigned to one of four groups:

    • Group 1: Participants switching to TLD, after taking prior anti-HIV medication that contains a NNRTI drug (a group of medicines scientifically known as non-nucleoside reverse transcriptase inhibitors, such as Efavirenz or Nevirapine).
    • Group 2: Participants switching to TLD, after taking anti-HIV medication that contains a PI drug (a group of medicines scientifically known as protease inhibitors, such as Lopinavir or Atazanavir).
    • Group 3: Participants taking TLD and receiving medication for TB (tuberculosis) that includes the drug rifampicin. These participants must be starting one or both of these medications when they enter the study.
    • Group 4: Participants starting TLD who have not taken anti-HIV medication before.

    There will be 1350 participants enrolled in the study.

    Purpose of the study

    To better understand risks and benefits of Tenofovir-Lamivudine-Dolutegravir (TLD) roll out in programs done in low- and middle-income countries.

    Requirements to enter the study

    Persons with HIV  age 10 years or older

    Body weight at least 30 kg

    Starting or switching to Tenofovir-Lamivudine-Dolutegravir (TLD)

    Currently receiving or planning to receive care in a program supported by the United States President’s Emergency Plan for AIDs Relief (PEPFAR).

    Study Treatment

    There will be no treatment provided through the study.

    Duration

    Each participant will be followed for 36 months.

  • A5368:Anti-PD-1 Antibody in HBV Infected on Suppressive Antiviral Therapy

    January 24, 2020 Alexis Sexton

    “Safety and Immunotherapeutic Activity of Cemiplimab in Participants with HBV on Suppressive Antiviral Therapy: A Phase I/II Ascending Multiple Dose Study”

    Brief Description: Scientists are looking at ways to cure Hepatitis B (HBV). This study will assess the safety and tolerability of cemiplimab administered in participants with HBV on suppressive antiviral therapy.

    Purpose of this Study: This study is trying to find out if cemiplimab is safe and well tolerated. Participants will receive multiple dose levels (0.3, 1.0, and 3.0 mg/kg) of cemiplimab administered as two infusions at weeks 6 and 12.

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

    • Have chronic HBV infection (defined as HBsAg positive) and under treatment for ≥12 months with tenofovir- or entecavir-containing therapy: tenofovir disoproxil fumarate (TDF), tenofovir alanfenamide (TAF), TDF/emtricitabine (FTC), TAF/FTC, or entecavir.
    • Be willing to continue HBV antiviral therapy throughout the study.
    • Have certain tests done.
    • Agree to use contraception/birth control methods.
    • Be 18 years old or older but less than 70 years.
    • Weight ≥40 kg.
    • Had evidence of limited or no evidence of fibrosis (F0-F2) by liver biopsy or noninvasive alternative method.
    • Be willing to sign the consent after discussion with the research staff.

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

    • Positive for the presence of Hepatitis C Virus.
    • Received investigational drug or device within 60 days prior to study entry.
    • Breastfeeding or pregnancy.
    • Known allergy/sensitivity or any hypersensitivity to components of study drug(s).
    • Active drug or alcohol use or dependence and other conditions that would interfere with adherence to study.
    • Acute or serious illness requiring systemic treatment and/or hospitalization within 35 days prior to study entry.
    • History of immunoglobulin IgG therapy or interferon (IFN) therapy within 12 months prior to study entry.
    • A male participant with a pregnant female partner.
    • Any vaccination within 30 days prior to entry.

    Treatment:

    • Multiple dose levels (0.3, 1.0 and 3.0 mg/kg) of cemiplimab administered as two infusions at weeks 6 and 12.

    Procedures:

    • Blood tests at clinic visits to check mainly hepatic and renal function.
    • Liver biopsy at study entry and at week 18 on study.
    • Leukapheresis for a group of participants.

    Duration of Study: Participants will be on study for up to 90 weeks (78 weeks following the last study drug infusion) with frequent safety evaluations.

  • A5357: A Study of Long-Acting Cabotegravir Plus VRC01LS to Maintain Viral Suppression in HIV-1-Infected Adults

    January 2, 2020 Alexis Sexton

    This study is for people with HIV who have an undetectable viral load. The study will evaluate the safety and effectiveness of a combination of two medications. The first drug is called long-acting cabotegravir (CAB), which will be given orally during Part 1 of the study and then as an injection every 4 weeks during Part 2 of the study. The second drug is called VRC07-523LS, which is a monoclonal antibody. A monoclonal antibody targets human proteins rather than attacking the virus directly. This drug will be given intravenously (directly into a vein) over about 15 to 30 minutes every 8 weeks.

    Why is this study being done?

    • The study will see if cabotegravir and VRC07-523LS work well when taken together to keep HIV levels low.
    • This study will also evaluate the safety of the drug combination.

    Who can join?

    People with HIV:

    • Between the ages of 18 and 65
    • On stable three-drug anti-HIV medications for a minimum of 8 weeks, with no history of switch due to virologic failure
    • With a CD4+ cell count greater than or equal to 350
    • With all HIV viral loads <50 copies within 2 years (one blip <200 OK), and at least two viral loads <50 copies within 12 months
    • With no current hepatitis B or C infection
    • Who have no history of seizures or treatment for seizures within the past 2 years
    • With susceptibility to VRC07-523LS based on assay done at screening

    What do I need to do in the study?

    Participants will be randomized to either:

    Step 1: All participants will discontinue their current anti-HIV medications except for “nukes” and start oral CAB.

    Step 2: Participants may receive CAB long-acting drug by injection every 4 weeks plus VRC07-523LS infusion by IV every 8 weeks for 48 weeks.

    Step 3: Participants will be switched back to a Standard of Care oral HIV regimen.

    Duration of Study: Participants will be on study for about 101 weeks.

    What treatments or drugs are involved with this study?

    The study provides oral and long-acting injectable cabotegravir and VRC07-523LS infusions. Standard of care oral medications will need to be locally sourced.

  • A5359: The LATITUDE Study

    May 17, 2019 pendari

    Investigating whether long-acting injectable medications will be more successful for people who are non-adherent to their HIV medications than oral regimens.

    Treatment Category:  Treatment Experienced

    Study Description

    This four-step study compares Long-Acting (LA) Injectable Antiretroviral Therapy (ART) to standard of care (SOC) oral ART in previously non-adherent individuals.

    Step 1 is the induction phase, and all participants receive study-provided SOC oral ART. Participants receive financial incentives for meeting study-specified goals.
    Step 2 is the randomization phase and participants are randomized 1:1 to receive LA ART or continue on SOC for 52 weeks.
    Step 3 is the crossover/continuation phase. Participants randomized to LA ART will continue that therapy, and eligible SOC participants will cross over to receive LA ART for 52 weeks.
    Step 4 is the observational phase that switches participants who received at least one LA ART injection and are no longer eligible for injections back to locally sourced oral SOC ART for 52 weeks.

    Study Status  

    Why is this study being done?

    • This study is investigating if LA injectable ART will be more successful for people who are non-adherent to their HIV medications than oral SOC regimens.
    • The main advantages of LA ART in this population include infrequent dosing and directly observed therapy. A challenge for participants is that, to be eligible to receive LA ART, they will need to attain virologic suppression through adherence to their SOC oral medications.
    • Financial incentives will be used during the first 20 weeks of the study to motivate participants to be adherent to an oral regimen until they are eligible to be randomized to either the LA ART arm or the SOC arm.

    Who can join?
    People living with HIV (PLWH) who are 18 years of age or older who

    • Have been prescribed anti-HIV medications (ART) for at least 6 months
    • Have an HIV viral load greater than 200 copies
    • Show evidence of non-adherence to their HIV medications by either:
      • Poor virologic response within the last 18 months (viral load greater than 200 copies at two time points at least 4 weeks apart)
      • Loss to clinical follow-up within the last 18 months, with ART non-adherence for at least 6 consecutive months
    • Have no active hepatitis B or C
    • Are willing to receive injections in the gluteus muscles (buttocks).

    What do I need to do in the study?

    Step 1: Induction (24 Weeks)
    All study participants will be prescribed an individualized oral study-provided ART regimen. In addition to financial compensation for attending study visits, participants will receive a financial incentive (bonus) if they attend their week 2 visit and achieve specific drops in their viral loads at weeks 4, 8, 12, 16, and 20. Participants whose viral load is <50 copies at week 20 will be eligible for randomization to Step 2 at their week 24 visit.

    Step 2: Randomization to LA ART Versus Oral SOC (52 Weeks)
    Participants will have a 50% chance of receiving either:

    LA ART Arm:
    Oral cabotegravir and oral rilpivirine daily for 4 weeks.
    –    During this 4-week oral phase, participants are monitored for side effects. Those who tolerate the oral medication will receive the LA form of cabotegravir and rilpivirine as intramuscular injections in the buttocks every 4 weeks for 48 weeks.

    OR

    SOC Arm:
    Continue taking SOC oral ART for 52 weeks.

    Step 3: LA ART Continuation/Crossover to LA ARV (52 weeks)
    LA ART Arm:
    Participants continue LA ART injections every 4 weeks for 52 weeks.

    SOC/Crossover Arm:
    Participants with an HIV RNA <50 copies at Step 2 week 48 or 52 are eligible to cross-over to LA ART.

    Step 4: Observation on SOC for Participants Who Received at Least One Dose of LA ART (52 weeks)
    This step is for participants that received at least one dose of LA ART and discontinued injections for any reason.

    Duration of Study:
    Steps 1-3 combined are a total of 128 weeks. Step 4 lasts 52 weeks.

    What treatments or drugs are involved with this study?
    The study provides oral and LA injectable cabotegravir and rilpivirine in Steps 1-3. Standard of care oral ART will need to be locally sourced.

  • A5321: Decay of HIV-1 Reservoirs in Participants on Long-Term Antiretroviral Therapy: The ACTG HIV Reservoirs Cohort (AHRC) Study

    May 17, 2019 pendari

    Studies differences and changes over time in HIV reservoirs (groups of HIV infected cells that ’hide’ from anti-HIV medications).  

    Why is this study being done? 

    To try to answer questions about the ways that HIV infection is controlledThis may have to do with a person’s viral load and CD4 countwhen they started their anti-HIV medications, and genetic factors.  

     Who can join? 

    You must be in one of the following three groups: 

    • Group 1: Participated in ACTG study A5276s or A5001 (if you were a part of A5001 you must have also participated in either ACTG 384, A5095, A5142, A5202, or A5257) 
    • Group 2: Began your anti-HIV medications during the very early part of your HIV infection  
    • Group 3: Had a viral load less than 500 copies/mL prior to starting any anti-HIV medications 

    you must also: 

    • Be HIV-infected man or woman, ≥ 18 years of age 
    • Be taking anti-HIV medications that have been controlling your viral load for 1-2 years (depending on which Group you will be in)  
    • Have never stopped your anti-HIV medications for more than 3 weeks 
    • Have no active hepatitis B or C infection, an autoimmune, disorder or condition requiring steroid therapy

    What do I need to do in the study? 

    Participants will attend visits twice a year for about seven years. At these visits, blood and a small amount of hair will be collected from all participants. Some participants who meet additional criteria may be asked to have two additional procedures: 

    • Rectal biopsy – a procedure that allows the collection of small pieces of rectal tissue  
    • Leukapheresis – a procedure to collect white blood cells

    These procedures are optional and will only start after a participant has been in the study at least six months. 

    What treatments or drugs are involved with this study? 

    You must be taking and planning to continue your current anti-HIV medications. These medications will not be supplied through this study. 

    Participants will be expected to stay in the study for about 7 years.

     

    A5341s: A5321 Sampling Substudy

     

    Longitudinal Sampling Substudy of A5321 is collecting information from measures of different HIV reservoirs, including where HIV can be found, whether different reservoirs have different amounts of HIV, the best way is to measure the amount of HIV in different reservoirs, and whether the amount of HIV found in one reservoir says anything about the amount of HIV in other reservoirs.

    Why is this substudy, A5341s, being done?

    This substudy will compare samples from different reservoirs to learn more about the following:

    • Where HIV can be found
    • Whether the amount of HIV is different in different reservoirs
    • What is the best way is to measure the amount of HIV in different reservoirs
    • Whether the amount of HIV found in any one reservoir can tell us anything about the amount of HIV in any of the other reservoirs

    Who can join the substudy, A5341s?

    A5321 participants are eligible to enroll in the A5341s substudy if they:

    • Agree to participate in one or more of the following groups:
      • Group A: lumbar puncture – cerebrospinal fluid (CSF) collected
      • Group B: leukapheresis – blood collected using a special procedure
      • Group C: rectal biopsy – tissue collected from the rectum
      • Group D: genital secretions – semen from men, vaginal cells and fluid from women
    • Have not had consecutive plasma HIV RNA values >200 copies/mL after 48 weeks on anti-HIV medicationsNOTE:    When the substudy A5341s first opens to enrollment, only people who are willing to be in Group A, Group B, or Group C (with or without being in one other group) may enroll. People who are only willing to be in Group D will not be able to enroll until later.

    What do I need to do in the substudy, A5341s?

    Participants enrolled in one or more groups will undergo the following procedures:

    • Group A: lumbar puncture – CSF collected once as part of A5321 and 4 times in A5341s (at about 6 to 12 month intervals)
    • Group B: leukapheresis –  large volume of blood collected 1 time
    • Group C: rectal biopsy – collected 2 times (at least 12 months apart)
    • Group D: genital secretions – collected 5 times (about every 6 months)

    All participants will also have blood and hair samples collected and neuropsychological testing performed approximately every 6 months.

    Participants will be expected to stay in the substudy A5341s for about 2 years while still remaining in the main study A5321. Some A5321 and A5341s visits can be combined.

    ACTG A5321: Decay of HIV-1 Reservoirs in Participants on Long-Term Antiretroviral Therapy: The ACTG HIV Reservoirs Cohort (AHRC) Study

    Study Description

    AHRC (pronounced “ARC”) is a study of differences and changes over time in HIV reservoirs (groups of HIV-infected cells that “hide” from anti-HIV medications).   Blood will be collected twice a year for about 7 years from HIV-infected participants on anti-HIV therapy.

    Study Status

    Enrolling

    Why is this study being done?

    This study is being done to try to answer questions about the ways that HIV infection is controlled. This may have to do with a person’s viral load and CD4 count when they started their anti-HIV medications, how soon after their HIV infection they started anti-HIV medications, and/or genetic factors.

    Who can join?

    800×600 HIV-infected men and women at least 18 years of age, who:

    • Participated in AIDS Clinical Trials Group (ACTG) study A5276s or A5001 and were not on anti-HIV medications at entry into the A5001 parent study (Group 1)
      OR
    • Started anti-HIV medications very shortly after HIV infection (Group 2)
      OR
    • Participated in ACTG study A5308 (Group 3)
    • Are taking anti-HIV medications that have been controlling their viral load for 1-2 years
    • Have never stopped anti-HIV medications for more than 3 weeks.
    • Have no active hepatitis B or C infection, autoimmune disorder, or condition requiring steroid therapy.

    What do I need to do in the study?

    Participants will attend visits twice a year for about 7 years. At these visits, blood and a small amount of hair will be collected.

    Participants who meet additional criteria will be asked to have one set of additional optional procedures at some point after they enter the study. The special procedures are a neurological assessment (some simple tests to measure your coordination and memory) and a lumbar puncture or spinal tap. The spinal tap will be done to collect some fluid from your spinal column; tests on this fluid can tell researchers about HIV in the brain. Anyone asked to participate in this part of the study will be given more information about it and will have an opportunity to ask questions before making a decision. You do not have to decide now.

    What treatments or drugs are involved with this study?

    Participants must be taking and planning to continue taking their current anti-HIV medications. These medications will not be supplied through this study.

    Is there anything else I need to know about this study?

    Separate but related fluid and tissue collections are planned as a substudy of A5321 known as A5341s (Longitudinal Sampling Substudy of A5321). Participants will undergo different types of procedures to help understand how and where HIV might remain even though the level of HIV in their blood has been very low while taking anti-HIV drugs. See above.

  • A5377: Tri-specific Antibody

    May 17, 2019 pendari

    The first study of a broadly neutralizing antibody called SAR441236 in humans, will determine if an infusion is safe and tolerable and will measure the amount of SAR441236 in the blood over time. It will also evaluate whether SAR441236 can reduce the amount of HIV in a person’s blood.

    Treatment Category:  Treatment Naïve and Treatment Experienced

    Study Description
    Antibodies that develop naturally against HIV recognize and attach to one part of the virus so that the body’s immune system can try to attack it. Antibodies are usually made by a person’s own immune system, but they can also be manufactured as a drug. SAR441236 has been manufactured to attach to three parts of the HIV virus at the same time, and to neutralize (or block) the ability of the virus to infect more cells.

    A5377 is the first study of SAR441236 in humans. This study will enroll two groups of people with HIV: Arm A—people who are on an anti-HIV regimen with an undetectable HIV viral load will receive either SAR441236 or placebo in four increasing dosing groups; and Arm B—people who have never received anti-HIV medications will receive SAR441236 in four increasing dosing groups.

    Why is this study being done?
    This study will determine if one infusion of SAR441236 is safe and tolerable, and will measure the amount of SAR441236 in the blood over time. The study will see if SAR441236 can reduce the amount of HIV in a person’s blood. Increasing dose levels and multiple infusions will be studied.

    Who can join?
    People with HIV who:

    • Are 18 to 70 years of age
    • Have no active Hepatitis B or C infection

    Arm A:

    • Have taken anti-HIV medications for at least 12 months
    • Have “undetectable” HIV viral load for at least 12 months
    • Have a CD4 count greater than 200

    Arm B:

    • Have never taken anti-HIV medications (including pre-exposure prophylaxis [PrEP])
    • Have an HIV viral load of 5000 to 100,000 copies
    • Have a CD4 count greater than 350
    • Are willing and able to start anti-HIV medications

    What do I need to do in the study?

    Arm A: Participants will be assigned to one of the following dosing groups, and will be randomly assigned (by chance) to receive one infusion of either:

    • 1 mg/kg SAR441236 or placebo
    • 3 mg/kg SAR441236 or placebo
    • 10 mg/kg SAR441236 or placebo
    • 30 mg/kg SAR441236 or placebo (four infusions, one every 12 weeks)

    Participants will continue to take their anti-HIV medications throughout the study.

    Arm B: Participants will be enrolled in one of the following dosing groups and will receive one infusion of:

    • 1 mg/kg SAR441236
    • 3 mg/kg SAR441236
    • 10 mg/kg SAR441236
    • 30 mg/kg SAR441236

    0.3 mg/kg SAR441236—this dosing group might or might not be included in the study

    Participants will start taking anti-HIV medications by Day 28 of the study.

    SAR441236 or placebo will be given as an infusion in the arm.

    On the day of the infusion, blood will be collected over 24 hours, so participants may need to stay in the clinic overnight. Participants will have blood collected for safety monitoring. When and if it is determined that a lower dose is safe, the next higher dosing group will be opened for enrollment. Most participants will be followed on study for 24 weeks after their infusion. Participants who receive multiple infusions will be followed for a total of 72 weeks.

    What treatments or drugs are involved with this study?
    SAR441236 and placebo will be provided through the study. Anti-HIV medications will not be supplied through this study.

  • A5128: US Genomic Sampling

    May 17, 2019 pendari

    Designed to develop a standard operating procedure to establish a storage bank for specimens for future HIV DNA analyses.

    Study Description

    Informed consent to use stored specimens for currently unspecified/ genetic analyses.

    Why is this study being done?

    To develop a standard operating procedure to establish a storage bank for specimens for future genetic (DNA) analyses.

    Who can join?

    Anyone enrolled in an ACTG study.

    What do I need to do in the study?

    Blood stored for future testing.

    What treatments or drugs are involved with this study?

    No treatment is provided by the study.

  • A5243: Non-US Genomic Sampling

    May 17, 2019 pendari

    Collecting blood and saliva samples from former and current ACTG study participants for future HIV-related genetic testing.

    Study Description

    This is a study to collect blood and saliva samples from former and current participants in AIDS Clinical Trial Group (ACTG) studies at non-U.S. sites.

    Why is this study being done?

    All samples will be stored for future HIV-related genetic testing. Any use of these samples will have to be approved both by the ACTG and by site Ethics Committees.

    Who can join?

    Former and current participants in ACTG studies at non-U.S. sites.

    What do I need to do in the study?

    Participants will be asked to sign a written informed consent indicating whether they are or are not willing to provide a saliva and a blood sample.

    At entry, participants who are willing to do so will provide a single saliva and a single blood sample. Participation in the study will end after the samples are collected.

    What treatments or drugs are involved with this study?

    No treatment will be provided through or required by the study.