Massachusetts General Hospital (MGH) CRS

A5377: Tri-specific Antibody

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.

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.

A5354: Effect of Antiretroviral Treatment Initiated During Acute HIV-1 Infection on Measures of HIV-1 Persistence and on HIV-1-Specific Immune Responses

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.

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.

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

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).

A5332: REPRIEVE Trial

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.

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

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.

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

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.

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

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.

A5401: ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies

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.

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)

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.

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

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.

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)

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.