Monoclonal Antibodies + ART for HIV Infection

Recruiting at 38 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Must not be taking: Immunomodulators, Corticosteroids

Disqualifiers: ASCVD, Hepatitis B, Hepatitis C, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining monoclonal antibodies—proteins that help the immune system fight viruses—with standard HIV treatment, known as ART (Antiretroviral Therapy), is safe and effective for people recently diagnosed with HIV. The trial aims to determine if this combination can delay the virus from becoming detectable and reduce the amount of virus hiding in the body. Individuals newly diagnosed with HIV who have not yet started treatment might be suitable candidates for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in HIV care.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does require that you have not used antiretroviral therapy (ART) within 60 days prior to study entry. Additionally, certain medications are prohibited, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of monoclonal antibodies VRC07-523LS and PGT121.414.LS is safe and well-tolerated in people. Studies have found that these antibodies, when used together, generally cause no major side effects. Participants had measurable levels of these antibodies in their blood, indicating proper processing by the body. The reviewed studies reported no significant negative effects linked to these treatments. This suggests they are safe for use in people, although further research is ongoing to fully understand their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HIV because they incorporate monoclonal antibodies, VRC07-523LS and PGT121.414.LS, which offer a novel approach compared to the traditional antiretroviral therapy (ART). Monoclonal antibodies are designed to target and neutralize the HIV virus more precisely, potentially leading to better control of the infection and reducing the viral load with fewer side effects. This precision targeting could enhance the effectiveness of ART by providing an additional layer of defense against the virus. The combination of these antibodies with ART represents a promising step forward in improving long-term outcomes for individuals living with HIV.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that using the monoclonal antibodies VRC07-523LS and PGT121.414.LS with antiretroviral therapy (ART) may effectively treat HIV. In this trial, one group of participants will receive VRC07-523LS and PGT121.414.LS combined with ART. These antibodies can lower HIV levels in the body by targeting and neutralizing the virus, potentially preventing its return after stopping treatment. Early results suggest that these antibodies, when combined with ART, reduce hidden virus levels and enhance the immune system's response to HIV. Overall, these treatments offer a promising way to better control HIV. ^{2 3 5 6 7}

Who Is on the Research Team?

Trevor Crowell, MD, PhD

Principal Investigator

U.S. Military HIV Research Program CTU

Are You a Good Fit for This Trial?

Adults aged 18-70 with recent acute HIV infection who haven't started antiretroviral therapy (ART) can join. They must have certain blood counts, agree to use barrier contraception or abstain from sex, and not be pregnant. People with severe allergies, active Hepatitis B/C, drug/alcohol dependence, or other conditions that could interfere with the trial cannot participate.

Inclusion Criteria

Step 1: Agreement to use two methods of contraception for persons able to become pregnant

Step 3: Has not met ART restart criteria

I have received all the required doses of the study treatment.

Exclusion Criteria

Step 1: History of severe allergic reactions or chronic urticaria

I have received immunoglobulin therapy before.

I have received a human or humanized monoclonal antibody treatment, not for COVID-19.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including delay in time to HIV-1 RNA ≥1,000 copies/mL and assessment of viral reservoirs

12 weeks

Bi-weekly visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term to assess sustained HIV remission

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ART
• PGT121.414.LS
• Placebo
• VRC07-523LS

Trial Overview The study is testing if adding combination HIV-specific broadly neutralizing antibodies (bNAbs) VRC07-523LS and PGT121.414.LS to standard ART in newly infected individuals can safely delay HIV rebound after treatment pause and reduce viral reservoirs compared to placebo plus ART.

How Is the Trial Designed?

Group I: Arm 1: VRC07-523LS + PGT121.414.LS + ART Experimental Treatment 3 Interventions

Group II: Arm 2: Placebo + ART Placebo Group 2 Interventions

ART is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in United States as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in Canada as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in Japan as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in China as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in Switzerland as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Combined antiretroviral therapy (cART) is highly effective in controlling HIV-1 replication and has significantly reduced morbidity and mortality among people living with HIV-1/AIDS, with about 60% of patients globally receiving this treatment.

Despite its effectiveness, challenges remain, particularly with latently infected CD4+ T cells that can lead to high viral loads if cART is interrupted, highlighting the need for new therapies that can reactivate and eliminate these cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past HIV-1 Medications and the Current Status of Combined Antiretroviral Therapy Options for HIV-1 Patients. Weichseldorfer, M., Reitz, M., Latinovic, OS.[2021]

Novel antiretroviral agents, such as capsid inhibitors and second-generation maturation inhibitors, show high potency and potential for extended-duration dosing, which could improve treatment adherence for people living with HIV.

Islatravir, a nucleoside reverse transcriptase translocation inhibitor, has demonstrated sustained drug levels in a phase I trial, while fostemsavir is now available for compassionate use in patients with multi-drug-resistant HIV, highlighting advancements in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Antiretroviral Agents. Cambou, MC., Landovitz, RJ.[2021]

In a study of 315 people living with HIV in Cameroon, those on highly active antiretroviral therapy (HAART) had a significantly higher prevalence of hypertension (36.44%) compared to those who were HAART-naïve (13.33%), indicating a potential side effect of HAART.

Specific HAART regimens, such as TDF/3TC/EFV and AZT/3TC/NVP, were associated with increased odds of hypertension, suggesting that monitoring blood pressure in patients on these treatments is crucial for managing their overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between highly active antiretroviral therapy (HAART) and hypertension in persons living with HIV/AIDS at the Bamenda regional hospital, Cameroon. Pangmekeh, PJ., Awolu, MM., Gustave, S., et al.[2022]

While combined active antiretroviral therapy (cART) has significantly improved the lives of HIV-infected individuals, it does not fully restore the immune system or eliminate the reservoir of HIV-infected cells, leading to ongoing health issues.

The review highlights promising immunotherapies, including cytokine therapies and monoclonal antibodies, that could enhance the effectiveness of cART by targeting the immune response and addressing the limitations of current treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic restoration in HIV-infected individuals. Kim, JM., Han, SH.[2011]

In a study of 185 HIV-2+ patients and 30,321 HIV-1+ patients, those with HIV-2 showed a significantly poorer recovery of CD4 cell counts after starting first-line combination ART, with an observed difference of 97 cells/mm3 after one year.

Even after adjusting for factors like pretreatment viral load, HIV-2+ patients had a mean CD4 cell increase that was 25 cells/mm3/year lower than that of HIV-1+ patients, highlighting the need for more effective treatment strategies for HIV-2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: a multinational, multicohort European study. Wittkop, L., Arsandaux, J., Trevino, A., et al.[2022]

Combination antiretroviral therapy (cART) is becoming increasingly effective due to the development of new antiretroviral agents and treatment regimens.

Despite these advancements, the long-term success of HIV/AIDS treatment is at risk due to the emergence of drug-resistant strains that can resist multiple agents and entire drug classes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: a literature review. Katusiime, C., Ocama, P., Kambugu, A.[2021]

A study of 2,753 patients showed that starting combination antiretroviral therapy (cART) after 1996 significantly improved CD4(+) T-cell counts and reduced the proportion of patients with detectable HIV viral loads over the first four years of treatment.

The likelihood of needing to switch treatments decreased from 53% for those starting cART between 1996-1999 to just 29% for those starting after 2008, indicating that newer cART regimens are more durable and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent trends in early stage response to combination antiretroviral therapy in Australia. McManus, H., Hoy, JF., Woolley, I., et al.[2021]

Combination antiretroviral therapy (cART) has transformed HIV-1 infection from a fatal disease to a manageable chronic condition, showcasing significant advancements in treatment over the past decade.

Recent developments in cART have improved its efficacy while reducing long-term toxicity, but the main challenge now is ensuring that this effective treatment is accessible to all individuals in need, with hopes for future HIV-1 eradication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination antiretroviral therapy. Domingo, P., Vidal, F.[2011]

The introduction of highly active antiretroviral therapy (HAART) has significantly improved survival rates for people with HIV-1, with the hazard ratio for death dropping from 0.47 in 1997 to 0.16 in 2001, indicating a substantial increase in life expectancy since HAART became widely used.

While injecting drug users showed higher mortality rates compared to men who have sex with men during the HAART era, the age-related risk of developing AIDS has diminished, suggesting that age is no longer as critical a factor in disease progression as it was before HAART.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of survival following HIV-1 seroconversion after the introduction of HAART. Porter, K., Babiker, A., Bhaskaran, K., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06812494

NCT06812494 | A Study of VRC07-523LS, PGT121.414.LS ... The hypothesis of the study is that the combination of VRC07-523LS and PGT121.414.LS and PGDM1400LS antibodies when administered via the intravenous (IV) route ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352301824002479

Safety, tolerability, pharmacokinetics, and neutralisation ... In this study, we tested a combination of two mAbs, VRC07-523LS and PGT121.414.LS, given as either intravenous or subcutaneous preparations to individuals ...

3. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/vrc07-523ls/patient

VRC07-523LS Patient Drug Record | NIH Purpose: The purpose of this study is to evaluate the safety, immunogenicity, and efficacy of therapeutic HIV vaccines in combination with the bNAbs PGT121, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04212091

Study Details | NCT04212091 | Evaluating the Safety, ... This study will evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in ...

5. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06987318

HIV/AIDS This study is an open-label, two-arm, multi-step phase I study evaluating a combination of two broadly neutralizing antibodies (bNAbs), VRC07-523LS and PGT121.

6. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT06517693

PGT121.414.LS Alone and in Combination With VRC07 ... The study is designed to assess the safety and pharmacokinetics (PK) profile of one and two subcutaneous (SC) doses of PGT121.414.LS alone or in combination ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9417124/

Safety and Pharmacokinetics of Monoclonal Antibodies ... VRC07-523LS and PGT121 were safe and well tolerated with detectable serum antibody concentrations. Subcutaneous administration of VRC07-523LS in combination ...