• A5364: A Phase I, Open-Label Study of the Safety and Ability of Broadly Neutralizing Antibodies 3BNC117-LS and 10-1074-LS in Combination to Durably Prevent Viral Relapse During a Monitored Analytical Treatment Interruption

    October 10, 2022 Alexis Sexton

    ACTG A5364: A Phase I, Open-Label Study of the Safety and Ability of Broadly Neutralizing Antibodies 3BNC117-LS and 10-1074-LS in Combination to Durably Prevent Viral Relapse During a Monitored Analytical Treatment Interruption


    Treatment Category: Experienced


    Study Description
    This is a Phase I, open-label, single-arm, multi-step study designed to evaluate the effects of the combination of long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS and 10-1074-LS in participants living with HIV who discontinue anti-HIV therapy (ART) during a monitored analytical treatment interruption (ATI), which is an extended period of time when not taking regular ART to control HIV.


    Study Status: Open to Accrual


    Why is this study being done?

    • To see if it is safe to give people 10-1074-LS and 3BNC117-LS, and to see if these study drugs cause any side
    • To evaluate the efficacy of the study drugs in preventing the return of HIV levels in the blood after interrupting ART.


    Who can join?

    • People with HIV between 18 and 70 years old.
    • On stable ART with an undetectable viral load for at least 48 weeks prior to study entry.
    • Body weight between 110 and 250 lbs.
    • Participants who can become pregnant must agree to use two methods of contraception during the
    • Be willing to temporarily stop taking ART medications.


    What do I need to do in the study?

    After screening, eligible participants will undergo leukapheresis (a procedure in which blood is collected from a vein in one arm, processed through an attached machine, and then returned through a vein in the opposite arm), and will be asked if they are interested in optional procedures (flexible sigmoidoscopy with rectal biopsy and/or lumbar puncture to collect spinal fluid). Three additional leukapheresis procedures will be done during the study.


    At study entry, participants will receive an infusion of 3BNC117-LS and an infusion of 10-1074-LS, and will discontinue ART 2 days later.


    Stopping ART is not recommended in the context of standard clinical care and poses some level of risk to the participant and sexual partner(s). However, for this research study, participants will be monitored closely while they are not taking ART. They will have to start taking ART again if blood tests show that it is necessary. The ATI can last up to 24 weeks of frequent visits to see if ART should be restarted.


    Each participant will be followed for 72 weeks.


    What treatments or drugs are involved with this study?

    10-1074-LS and 3BNC117-LS are antibodies to HIV. Many antibodies are naturally made by the body and help fight diseases. 10-1074-LS and 3BNC117-LS are made in a laboratory. They are called “monoclonal antibodies,” which means that they are made up of many copies of one single antibody.

  • ACTG A5383: Randomized, Controlled Trial to Evaluate the Anti-inflammatory Efficacy of Letermovir (Prevymis) in Adults with Human Immunodeficiency Virus (HIV)-1 and Asymptomatic Cytomegalovirus (CMV) Who Are on Suppressive ART and Its Effect on Chronic Inflammation, HIV Persistence, and Other Clinical Outcomes (ELICIT)

    June 23, 2022 Alexis Sexton

    Brief Description:
    This study will include 180 participants. Participants will have HIV and Cytomegalovirus (CMV). CMV is common virus that many people living with and without HIV have been exposed to. You do not need to know if you have CMV to be considered for study participation. About half of the study participants will be given study medication to be taken once daily for 48 weeks. The study medication will be letermovir, an FDA approved medication to prevent CMV. The other half of
    participants will not receive any additional medication. The study will last about 1 year and 2 months.
    Purpose of this Study:
    To learn whether people living with well controlled HIV and symptom free CMV can reduce inflammation by taking a drug approved by the FDA to prevent CMV disease.
    To Enter the Study, the following must be true about you:

    • HIV positive, ≥40 years of age
    • On continuous anti-HIV medications for at least 48 months with no interruptions >7 days
    • At least 48 months of undetectable viral loads, although a one-time, low-level viral load is OK
    • Have not made significant change in HIV medication in the past 12 weeks, or plan to make changes during study participation
    • No heart arrythmias/ irregular heart beats
    • No active Hepatitis B or hepatitis C within 24 weeks
    • Not currently using any of the following HIV medications: efavirenz, nevirapine, etravirine, lopinavir/ritonavir, or once a day dosing of raltegravir (twice a day dosing is OK)
    • While people with any CD4 count are eligible, the study is particularly interested in recruiting people with low CD4 counts (i.e., <350 cells/mm3)
    • While people of all gender identities are eligible, the study is particularly interested in recruiting cis-gender women and transgender women receiving gender-affirming hormones

    There will be treatment provided in this study. Letermovir is a pill given by mouth once a day that is FDA-approved to prevent CMV disease. There are two study treatment groups.
    You will have a 50/50 chance of going into one of the two groups. Participants in one group will get letermovir and participants in the other group will not get any additional medications.

  • A5355: Phase II, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of a Modified Vaccinia Ankara (MVA)-based Anti-Cytomegalovirus (CMV) Vaccine (Triplex®) in Adults with Both Human Immunodeficiency Virus (HIV)-1 and CMV Who Are on Potent Combination ART with Conserved Immune Function

    June 2, 2022 Alexis Sexton

    Brief Background and Description: Since the early days of the HIV epidemic cytomegalovirus (CMV) has been one of the most common and devastating opportunistic infections (OIs) experienced by people with HIV. CMV is a common virus that usually causes few, mild, or no symptoms and typically remains in the body for life; in people with weakened immune systems, however, CMV can cause more serious symptoms affecting the eyes, lungs, liver, esophagus, stomach, and intestines ). HIV and CMV can work together against our bodies’ defenses, making transmission of each virus easier. We would like to change this.

    In this study, you will be randomized to one of the study treatment arms. You will receive either Triplex® study vaccine or placebo by injection into the muscle of your shoulder 2 times; once when you enter the study and again about 4 weeks later.

    Purpose of this Study: The purpose of this study is to see if an investigational vaccine for CMV (called Triplex®) is safe when given to people with both HIV and CMV. This study will also collect information on the effectiveness of Triplex® to reduce inflammation and immune activation markers compared to a placebo. This will be the first time that this type of information will be collected. You should be aware that the current standard of care for individuals with both HIV and CMV includes effective treatment for HIV but does not include treatment of CMV with either medication or vaccination – unless there is evidence that the CMV is causing or contributing to illness.

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

    • Living with HIV-1 and with cytomegalovirus (CMV).
    • Be between 18 and 65 years old.
    • On an anti-HIV medications that are controlling your HIV for at least the past year.
    • Agree to use contraception/birth control methods if capable of becoming pregnant or impregnating someone else.

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

    • Use of anti-CMV drugs within the past 2 weeks.
    • Currently have hepatitis B or hepatitis C
    • Currently have a sexually transmitted infection (such as, gonorrhea, syphilis, or chlamydia)
    • History of CMV disease and symptoms within the past 12 months.
    • Receipt of any vaccine (including for COVID-19) within the previous 4 weeks.
    • 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.

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


    When you enter this study, you will be randomized (assigned by chance, as if by roll of dice) to one of two study groups. You will have double the chance of receiving Triplex® versus the placebo. You must continue to take your anti-HIV drugs throughout the study.


    • Blood and urine tests at scheduled clinic visits for safety evaluations and other research testing.
    • Questionnaires asking for information on adherence to ART and use of other drugs.
    • For 4 weeks following each study injection you will complete a daily study diary (which is also known as a study vaccination report card); you will need to take and record your body temperature for the first 5 days each time.
    • At several of the clinic visits, saliva, rectal swabs, and/or genital fluid (semen or vaginal swab) will be collected.

    Duration of Study: About 2 years (96 weeks). In the first month of the study, you will have 2 study visits and 2 telephone contacts with clinic staff. After that, you will have 5 more visits over the next 16 months. After you have been on the study for about 2 years (about 4 months after your last study visit), your participation will end with a phone call from the clinic staff.

  • 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.


    • 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).


    • 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

    ACTG A5391: Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide (The Do IT Study)


    Treatment Category:  Treatment Experienced


    Study Description

    Weight gain after starting HIV therapy is common, but recent studies have found that some people with HIV (PWH) who are taking an integrase inhibitor (INSTI) combined with a tenofovir alafenamide (TAF) regimen may gain more weight than people taking other drug combinations.  A rising number of PWH are overweight or obese, and a higher body mass index (BMI) increases the risk for diabetes, heart disease and stroke.


    This study will include PWH who have been virally suppressed on a regimen consisting of an integrase inhibitor (INSTI) and TAF/FTC or TAF/3TC, and have a BMI of 30 kg/m2 (the cut-off for obesity) or greater. This research study is trying to find out if they could gain less weight, or maybe lose weight, after switching to a regimen containing doravirine (DOR) with TAF/FTC (or TAF/3TC), or DOR with the related medication tenofovir disproxil (TDF/FTC [or TDF/3TC]) as compared to continuation of their current INSTI plus TAF regimen.

    Study Status 

    Why is this study being done?


    • To see if obese PWH on an INSTI-containing regimen can either reduce their rate of weight gain over time or even lose weight with a change to a different regimen.


    Who can join?


    • People living with HIV-1 who are at least 18 years of age
    • Currently on an Integrase Inhibitor (INSTI) containing regimen (bictegravir, dolutegravir or raltegravir) plus TAF/FTC (or TAF/3TC) for at least 48 weeks
    • HIV viral load less than 50 copies
    • Have a body mass index (BMI) at least 30 kg/m2.
    • No plans to undergo weight loss surgery or to start significant exercise, diet, or medications affecting weight (e.g., structured weight loss programs such as Weight Watchers)


    What do I need to do in the study?


    Participants will be randomized to one of three study groups:

    Group 1: DOR and continue taking TAF/FTC (or TAF/3TC)

    Group 2: DOR and switch TAF to TDF/FTC (or TDF/3TC)

    Group 3: Continue current INSTI+TAF/FTC (or TAF/3TC)


    Study procedures include blood and urine tests, questionnaires about adherence to medications, diet and exercise habits, and DEXA Scans to measure lean muscle, body fat and bone density.


    Duration of Study:

    Participants will be on study treatment for 48 weeks.  Follow-up visits occur at Weeks 4,12,24,36, and 48.


    What treatments or drugs are involved with this study?

    Doravirine, which 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, will be provided by the study.


    NRTIs will need to be obtained by prescription from primary care provider.



  • A5343: A Trial of the Safety, Tolerability, and Pharmacokinetics of Bedaquiline and Delamanid, Alone and in Combination, among Participants Taking Multidrug Treatment for Drug-Resistant Pulmonary Tuberculosis

    February 20, 2020 Alexis Sexton

    This is a randomized study, which means, by chance, you will be in one of three groups. You have an equal chance of being assigned to a group like flipping a coin. A5343 is an open label clinical trial, which means you will know which group you are in and what medications you will be taking.

    This study will compare three treatment arms for people who have pulmonary multidrug resistant tuberculosis (MDR-TB). Pulmonary MDR-TB is a form of tuberculosis (TB) in the lung that is resistant to two or more of the primary drugs used for the treatment of TB (isoniazid and rifampin).

    You will receive standard treatment for MDR-TB plus one or two new drugs for TB, called bedaquiline (BDQ) and delamanid (DLM). Throughout the study, you will be monitored to make sure that there are no safety concerns. Your heart will be monitored closely to make sure it is safe to give the drugs together.

    Purposes of the Study:

    This study looks at how the two new drugs fight MDR-TB when used alone with other TB drugs or used together. It looks at how the TB drugs work inside the body when you take them. It also looks at how safe and well tolerated these two drugs are in people.. Multiple times throughout the study, blood samples and an ECG, a test that measures the electrical activity in your heart, will be done to monitor the safety of the drugs.

    Requirements to Enter Study:

    Inclusion Criteria: To be in the study, you must:

    • Be age 18 or older
    • Have MDR-TB in your lungs and be on treatment less than 8 weeks
    • Not be pregnant or breastfeeding
    • Use an approved form of birth control for both men and women
    • For persons with HIV : CD4 count above 100 cells/mm3 (CD4 cells are a kind of white blood cell that are a measure of the immune system)
    • Taking treatment for MDR-TB before joining the study
    • Willing to stay in hospital for at least 2 months
    • Able to take pills by mouth
    • Consent in writing to be in the study

    Exclusion Criteria: You cannot be in the study if you:

    • Have MDR-TB that does not involve the lungs
    • Have received BDQ or DLM in the past
    • Have any allergies to the study drugs
    • Are actively drinking alcohol or using drugs
    • Have heart problems or other serious illness
    • Require or may require the use of certain drugs to treat HIV at the same time you are taking study drugs
    • Require or may require the use of certain drugs, including, but not limited to, clofazimine and moxifloxacin, from 48 hours prior to study entry through 4 weeks after stopping study drugs

    Study Treatment:

    The treatment arms are:

    • Arm 1: BDQ (comes as a tablet to take by mouth)
    • Arm 2: DLM (comes as a tablet to take by mouth)
    • Arm 3: Both BDQ and DLM (as above)

    The duration and doses will be explained by the study nurse or study doctor.

    Length of Study:

    24 weeks on study treatment, followed by 104 weeks follow-up, for a total length of 128 weeks

    Number of Participants:

    Up to 84 people will enroll in this study

  • A5300B/I2003B: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


    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.

    Document list:


    A5300B/I2003B V3 Final Protocol dated March 31, 2020

    A5300B/I2003B V3 Manual of Procedures dated May 6, 2022

    A5300B/I2003B V3 Lab Processing Chart dated May 3, 2022

  • 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.


    Each participant will be followed for 36 months.