Open Studies

As a clinical trials unit, both the Alabama and Matero CRS units conduct National Institutes of Health (NIH) funded research through the National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) network groups: AIDS Clinical Trials Group (ACTG), the HIV Vaccine Trials Network (HVTN), and the HIV Prevention Trials Network (HPTN). Alabama CRS also conducts UAB investigator-initiated basic science research and pharmaceutical-sponsored clinical trials.

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.

Why is this study being done?

• The study will see if cabotegravir and VRC07-523LS work well when taken together to keep HIV levels low.
• This study will also evaluate the safety of the drug combination.

Who can join?
People with HIV:

• Between the ages of 18 and 65
• On stable three-drug anti-HIV medications for a minimum of 8 weeks, with no history of switch due to virologic failure
• With a CD4+ cell count greater than or equal to 350
• With all HIV viral loads <50 copies within 2 years (one blip <200 OK), and at least two viral loads <50 copies within 12 months
• With no current hepatitis B or C infection
• Who have no history of seizures or treatment for seizures within the past 2 years
• With susceptibility to VRC07-523LS based on assay done at screening

What do I need to do in the study?
Participants will be randomized to either:

STEP 1
All participants will discontinue their current anti-HIV medications except for “nukes” and start oral CAB.

STEP 2
Participants may receive CAB long-acting drug by injection every 4 weeks plus VRC07-523LS infusion by IV every 8 weeks for 48 weeks.

STEP 3
Participants will be switched back to a Standard of Care oral HIV regimen.

DURATION OF STUDY
Participants will be on study for about 101 weeks.

What treatments or drugs are involved with this study?
The study provides oral and long-acting injectable cabotegravir and VRC07-523LS infusions. Standard of care oral medications will need to be locally sourced.

Investigating whether long-acting injectable medications will be more successful for people who are non-adherent to their HIV medications than oral regimens.

Study Description:
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
Step 1 is the induction phase, and all participants receive study-provided SOC oral ART. Participants receive financial incentives for meeting study-specified goals.

STEP 2
Step 2 is the randomization phase and participants are randomized 1:1 to receive LA ART or continue on SOC for 52 weeks..

STEP 3
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
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 oral SOC ART for 52 weeks.

Why is this study being done?

This study is investigating if LA injectable ART will be more successful for people who are non-adherent to their HIV medications than oral SOC regimens.

The main advantages of LA ART in this population include infrequent dosing and directly observed therapy. A challenge for participants is that, to be eligible to receive LA ART, they will need to attain virologic suppression through adherence to their SOC oral medications.

Financial incentives will be used during the first 20 weeks of the study to motivate participants to be adherent to an oral regimen until they are eligible to be randomized to either the LA ART arm or the SOC arm.

Who can join?

• People living with HIV (PLWH) who are 18 years of age or older who
• Have been prescribed anti-HIV medications (ART) for at least 6 months
• Have an HIV viral load greater than 200 copies
• Show evidence of non-adherence to their HIV medications by either:
• Poor virologic response within the last 18 months (viral load greater than 200 copies at two time points at least 4 weeks apart)
• Loss to clinical follow-up within the last 18 months, with ART non-adherence for at least 6 consecutive months
• Have no active hepatitis B or C
• Are willing to receive injections in the gluteus muscles (buttocks).

What do I need to do in the study?

STEP 1: Induction (24 Weeks)
All study participants will be prescribed an individualized oral study-provided ART regimen. In addition to financial compensation for attending study visits, participants will receive a financial incentive (bonus) if they attend their week 2 visit and achieve specific drops in their viral loads at weeks 4, 8, 12, 16, and 20. Participants whose viral load is <50 copies at week 20 will be eligible for randomization to Step 2 at their week 24 visit.

STEP 2: Randomization to LA ART Versus Oral SOC (52 Weeks)
Participants will have a 50% chance of receiving either:

LA ART Arm:
Oral cabotegravir and oral rilpivirine daily for 4 weeks.
– During this 4-week oral phase, participants are monitored for side effects. Those who tolerate the oral medication will receive the LA form of cabotegravir and rilpivirine as intramuscular injections in the buttocks every 4 weeks for 48 weeks.

OR

SOC Arm:
Continue taking SOC oral ART for 52 weeks.

STEP 3: LA ART Continuation/Crossover to LA ARV (52 weeks)

LA ART Arm:
Participants continue LA ART injections every 4 weeks for 52 weeks.

SOC/Crossover Arm:
Participants with an HIV RNA <50 copies at Step 2 week 48 or 52 are eligible to cross-over to LA ART.

STEP 4: Observation on SOC for Participants Who Received at Least One Dose of LA ART (52 weeks)
This step is for participants that received at least one dose of LA ART and discontinued injections for any reason.

Duration of Study:
Steps 1-3 combined are a total of 128 weeks. Step 4 lasts 52 weeks.

What treatments or drugs are involved with this study?
The study provides oral and LA injectable cabotegravir and rilpivirine in Steps 1-3. Standard of care oral ART will need to be locally sourced.

Short Title:
The Slim Liver Study

Brief Description:
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.

Purpose of this Study:

The purpose of this study is to evaluate the safety and tolerability of a drug called semaglutide and to see if it can reduce the amount of fat stored in the liver.

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

• Living with HIV with 2 HIV viral loads less than 50 copies in the last year and a CD4 T-cell count of at least 200
• On your current HIV medications for at least 24 weeks
• Willingness to have MRI scans
• Agree to use contraception/birth control methods (if needed)
• Able to store semaglutide in a cool location
• Be 18 years old or older
• Be willing to sign the consent after discussion with the research staff
• Be willing to give yourself an injection once a week

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

• Hepatitis B or C Virus infection (not previously treated)
• Any plans to change diet or exercise significantly during the study period
• Breastfeeding, pregnancy, or plans to become pregnant while on study
• Liver disease with cirrhosis
• Current diabetes mellitus
• Chronic pancreatitis
• Prior gastric (stomach) surgery (lab band, gastric sleeve or gastric bypass surgery) or plans to undergo one of these surgeries in the near future
• High alcohol use

Procedure:

• Blood tests at clinic visits
• Stool collections
• MRI scans
• Adherence monitoring, physical function assessment, food diary, and questionnaires

Duration of Study:
Approximately 48 weeks

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 Criteria:
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 of Study:
72 Weeks

Weight gain after starting antiretroviral therapy (ART) is common, but recent studies have found that some people living with HIV (PLWH) who are taking an integrase strand transfer inhibitor (INSTI) combined with tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir alafenamide/lamivudine (TAF/3TC) may gain more weight than people taking other drug combinations. A rising number PLWH are overweight or obese. Higher BMI and weight gain on ART increase the risk for diabetes, heart disease and stroke. Researchers are looking to see if PLWH who have gained a significant amount of weight after starting or switching to an INSTI-containing regimen, can either reduce their rate of weight gain over time or even lose weight with a change to a different ART regimen. This study will include participants who are living with HIV-1, who have been virally suppressed for > 48 weeks on a regimen consisting of an INSTI and TAF/FTC or TAF/3TC and who have experienced > 10% weight gain since the initiation of this ART regimen.

Purpose of the Study:
This research study is trying to find out if PLWH who had > 10% weight gain after starting an antiretroviral therapy (ART) regimen that included an INSTI in combination with TAF/FTC (or TAF/3TC) could gain less weight, or maybe lose weight, after switching to an ART regimen containing doravirine (DOR) with either TAF/FTC (or TAF/3TC), or the related medication tenofovir disoproxil fumarate/emtricitabine (TDF/FTC [or TDF/3TC]). DOR 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. In multiple studies, DOR was shown to be just as effective as INSTI medications for treating HIV.

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

• Living with HIV-1.
• Be ≥ 18 years old.
• Currently on an Integrase Inhibitor (INSTI) containing regimen (BIC, DTG or RAL), with > 48 weeks INSTI+TAF/FTC (or TAF/3TC) dosing prior to study entry.
• Have experienced > 10% weight gain in the 1-3 years after starting these medications.
• Have a body mass index (BMI) >5 kg/m2.
• Have study related tests done, including a DEXA Scan (X-Ray Scan measuring measure lean muscle, body fat and bone density).
• Agree to use contraception/birth control methods if capable of becoming pregnant.
• Be willing to change ART if randomized to Arms 1 or 2.

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

• 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.
• Plans to undergo weight loss surgery or to start significant changes to your diet or exercise habits

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

Intervention:

When you enter this study, you will be randomized (assigned by chance, as if by roll of dice) to one of three study groups. Because the randomization is equal, you will have a 33% chance of being in any of the following study groups:

• Group 1: You will continue taking TAF/FTC (or TAF/3TC) but will stop your INSTI and take DOR; your ART will be DOR+TAF/FTC (or TAF/3TC) for 48 weeks.
• Group 2: You will stop your INSTI and TAF/FTC (or TAF/3TC) and will switch to DOR+TDF/FTC (or TDF/3TC) for 48 weeks.
• Group 3: You will continue your current ART of an INSTI+TAF/FTC (or TAF/3TC) for 48 weeks.

Procedures:

• Blood and urine tests at scheduled clinic visits for safety evaluations and other research testing.
• Questionnaires asking for information on adherence to ART and diet and exercise habits.
• DEXA Scan (Dual-Energy X-Ray Absorptiometry) to measure lean muscle, body fat and bone density.

Duration of Study:
Almost 1 year (48 weeks). Follow-up visits will occur at Weeks 4, 12, 24, 36 and 48 (study completion).