Johns Hopkins University CRS

A5359: The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE - A Phase III Study to Evaluate Long-Acting Antiretroviral Therapy in Non-adherent HIV-Infected Individuals

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 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 injectable ART (cabotegravir and rilpivirine injections) 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 SOC oral ART for 52 weeks.

A5357: A Study of Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) to Maintain Viral Suppression in Adults Living with HIV-1

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.

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.

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

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.

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.