studies

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

Treatment:
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.

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.

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

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
  • 1^st dose will be taken in the morning; this will not be supplied by the study
  • 2^nd 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.

“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.