• 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

  • A5366: Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation with Histone Deacetylase Inhibitors

    February 11, 2020 Alexis Sexton

    While antiretrovirals known as ARV’s (group of medicines used to treat HIV) have provided very effective treatment of HIV, cure of HIV from the body has not been possible.  One of the reasons may be due to virus hiding in resting (or ‘latent’) immune cells. This reservoir (the hidden virus) is able to reproduce itself and serves as source of infection if ARV’s are stopped. Some investigational medications have been shown to wake up latent (sleeping) immune cells allowing them to get rid of the virus they have inside them. However, these therapies are only partly effective and results vary in different people. Preliminary studies have shown that these therapies may be less effective in women due to female hormones.

    This study will evaluate one of the medications (Vorinostat) that have been shown to reverse latency in combination with another medication (Tamoxifen) that researchers hope will enhance that effect, specifically in women.

    Purpose of this Study: 

    The primary purpose of this study is to see if Tamoxifen given with Vorinostat is safe. It will also study if Tamoxifen will enhance the ability of Vorinostat to reverse latency in post-menopausal women.

    Basic requirements to Enter Study:

    • HIV-1 positive women between 18 and 65 years of age (up to 66th birthday)
    • Post-menopausal (either >18 with both ovaries removed or >40 with no period in the last 2 years)
    • CD4 count >300 cells/mm3 (CD4 cells are a kind of white blood cell that are a measure of the immune system)
    • On ARV’s for at least 2 years with undetectable viral loads
    • No active Hepatitis B or C
    • No history of cancer, blood clot or stroke
    • Not currently smoking or taking hormonal therapy

    Treatment:

    At entry, participants will be randomized to receive open label Tamoxifen 20mg by mouth daily (20 participants), or no Tamoxifen (10 participants) for the first 5 weeks. All participants will then receive 2 doses of 400mg each Vorinostat by mouth separated by 72 hours.

    Duration of Study:

    Up to 9 weeks per participant after a screening period of up to 90 days.

  • A5361s: Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE)

    February 11, 2020 Alexis Sexton

    Aging with HIV may be associated with an earlier development of frailty (weakness) or disability, including difficulties in tests of strength or walking speed. Few treatments have been shown to prevent or slow these impairments in people with or without HIV. Some studies have suggested that the class of drugs called statins, such as pitavastatin, might be helpful in slowing frailty or disability. This might happen by decreasing fat within the muscle, or by decreasing inflammation markers in the blood. This study uses the REPRIEVE Trial (A5332) and the REPRIEVE Mechanistic Substudy (A5333s) to study the impact of pitavastatin on muscle.

    Requirements to enter the Study:

    • You must already be enrolled in REPRIEVE trial (A5332) and the REPRIEVE Mechanistic Substudy (A5333s)
    • Taking pitavastatin or placebo as part of REPRIEVE (A5332)
    • Willing to complete study procedures

    Study Procedures

    As part of A5361s, muscle strength and muscle function will be measured at yearly visits. Tests will include repeated chair rises, hand grip strength test, standing balance test and a 12 foot (4 meter) timed walk. Participants will also be asked questions about their physical activity.

    CT scans (done already in A5333s) will be looked at carefully for muscle size and fat amount and blood samples (collected in A5332) will be analyzed for changes in biomarkers. No additional CT scans or blood will be collected on A5361s.

    Duration of Study:

    Participants will be followed for 48 months from the date of enrollment into A5332. Based on their date of enrollment into A5332, participants may be followed between 24 to 48 months.

  • A5332: REPRIEVE Trial

    February 11, 2020 Alexis Sexton

    In this study, people between the ages of 40 and 75 with HIV will be randomized (like flipping a coin) to take the pill pitavastatin OR a placebo (non-active pill) to see if pitavastatin can help prevent heart disease and death in people who are taking HIV medication. You will not know if you are taking pitavastatin or placebo. The REPRIEVE trial will enroll about 7500 people from several countries.

    Purpose of this Study:

    HIV causes inflammation (irritation) inside the body that cannot be felt but can be measured. Inflammation may contribute to diseases such as heart disease that have become some of the leading causes of death in people with HIV. HIV medications can lower inflammation somewhat, however sometimes the levels of inflammation can remain higher compared to people who do not have HIV.

    Statins (name of the group of medicines that pitavastatin belongs to) are used to lower the levels of cholesterol and triglycerides (fat in the blood) that people make. Studies have shown that statins may have other benefits. For example, heart disease and the levels of inflammation can be lowered by statins.

    Pitavastatin is a statin that, along with a diet, has been approved by the US Food and Drug Administration for the treatment of high cholesterol. It also lowers triglyceride levels in the blood.

    The main purpose of this clinical trial is to see if pitavastatin can prevent heart disease and heart disease related deaths in people with HIV who are taking HIV medications.

    Requirements to Enter Study: The study coordinator will review all of the criteria necessary to be eligible for the study with you. Listed below are a few key points.

    • Persons with HIV who are between the ages of 40 and 75.
    • On antiretroviral therapy (ART, medicine to treat HIV) for at least 6 months prior to study entry.
    • CD4+ cell count >100. (CD4 cells are a kind of white blood cell that are a measure of the immune system)
    • Must not be pregnant or planning to become pregnant.
    • No history of cardiovascular disease (history of heart attack or stroke, etc.).
    • No history of cancer in the last year.
    • Not currently using a statin drug.

    Treatment: Participants will be randomized (like flipping a coin) to take either:

    • Pitavastatin 4 mg one pill daily with or without food or
    • Placebo for pitavastatin one pill daily with or without food

    Duration of Study: You will be in this study for about 36 to 96 months depending on when you enroll in the study. You will need to be seen in clinic for a screening visit, an entry visit, one month later, and then every 4 months.

  • A5322: Long-Term Follow-up of Older HIV-infected Adults in the ACTG: Addressing Issues of Aging, HIV Infection and Inflammation (HAILO)

    February 11, 2020 Alexis Sexton

    You are being asked to take part in this research study because you are infected with HIV, the virus that causes AIDS, and were previously followed in the ALLRT (A5001) study and are 40 years of age or older. This study, A5322 (also known as the HAILO study), is a long-term follow-up study of persons who have HIV and received their first treatment for HIV known as antiretroviral medications, in certain clinical trials that were done by the AIDS Clinical Trials Group (ACTG).

    Purpose of this Study: 

    The purpose of this study is to help us learn about how HIV , aging and the immune system (how your body fights infection) all interact with each other to see how they relate to the development of illnesses such as kidney disease, cancer, and diabetes. This study will also see if treating people with HIV for these otherillnesses works as well as treating people without HIV for the same illness.

    Requirements to Enter Study:

    -PersonsParticipants 40 years of age and older who werebeing actively followed in the ALLRT (A5001), or recently completed follow-up in ALLRT, at the time of enrollment in A5322.

    -Received their first HIV treatment in an ACTG protocol and then enrolled intothe ALLRT parent protocol.

    -Eligible participantspartcipants must agree to be followed long-term to observe the aging process and for outcomes known as endpoints that are either clinical (you have a disease or health problem), virologic (meaning how your HIV responds to treatment) or  immunologic (meaning how your immune system reacts)while taking long-term treatment with HIV medicine.

    -Planned enrollment to include approximately 22% female participantssex participants (corresponding to the

    proportion of female sex participantsparticipants aged 40 years and older being followed in the ALLRT study).

    -Ability to commit to the long-term study requirements.

    Treatment: 

    Treatment for HIV must be arranged outside of the A5322 protocol. No treatment is given through the A5322 protocol.

    Special Testing:

    -As in ALLRT, participants will have the Neuroscreen at entry into A5322 and every 48 weeks thereafter.  This includes both Neurocognitive testing (i.e., digit symbol, HVLT-revised) and Neuropathy testing (i.e., tendon reflexes and vibratory sensation testing). -In addition, there will be a frailty assessment which will be performed for all participants enrolled in A5322. This consists of a hand grip assessment (measure of hand strength) followed by a 4-meter timed walk , along with several interviewer-administered questions on weight loss, physical activity and exhaustion.

    -Participation in A5322’s substudy (A5323s: Inflammation in the Functional Capacity: Trajectory of those Aging with HIV-Infection [FIT Substudy]) which is Optional. Participants enrolled in both A5322 and A5323s will complete the entire physical function battery which is detailed below:

    Grip Strength (A5322 and A5323s)

    4-meter Walk (A5322 and A5323s)

    Single Chair Rise (A5323s only)

    Repeated Chair Stands (A5323s only)

    Standing Balance Test (A5323s only)

    400-meter Walk (A5323s only)

    Duration of Study:

    Participants will be followed for 366 weeks (7 years).

  • A5354: Early ART in Acute HIV

    May 17, 2019 pendari

    Will evaluate whether starting antiretroviral drugs very early in HIV infection will limit the virus from getting into hidden areas of the body (reservoirs) and change how the immune system helps to control the virus.

    Study Description
    This study will include people who have very recently been infected with HIV and will start anti-HIV (antiretroviral) drugs right away to see how this may change HIV’s impact on the body.

    Why is this study being done?
    This study is trying to find out if starting antiretroviral drugs very early in HIV infection will change the following:

    • Limit the virus from getting into hidden areas of the body (“reservoirs”).
    • Change how the immune system helps to control the virus.

    What we mean by very early is even before the blood shows that antibodies have been made, or just at the time antibodies are starting to be found in the blood.

    Who can join?
    Men and women who:

    • Are at least 18 years old
    • Have had certain lab tests done that confirm very early HIV infection
    • Are willing to take antiretroviral drugs right away to treat HIV.

    What do I need to do in the study?
    Participants will start elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) single-tablet regimen (often called “Genvoya”) within 24 hours but no later than 48 hours after entering the study.

    Blood tests will be done at all clinic visits to check HIV blood levels and immune cells.

    Some participants may be approached to take part in additional optional procedures later in the study to check out the “reservoirs” where the virus might hide:

    • Leukapheresis or large volume blood collection
    • Lumbar puncture (cerebrospinal fluid) (also called a “spinal tap”)
    • Gut biopsy (also called “sigmoidoscopy with biopsy”)

    The duration of the study is up to 72 weeks (a year and a half).

    What treatments or drugs are involved with this study?
    The study treatment that will be provided through the study is EVG/COBI/FTC/TAF single-tablet regimen. Other antiretroviral drugs are allowed if EVG/COBI/FTC/TAF is not the ideal drug for a particular person.