Monoclonal Antibodies + ART for HIV Infection

Recruiting in Palo Alto (17 mi)

+35 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

A5388 is a phase II, two-arm, randomized, double-blind, placebo-controlled study that will enroll 48 antiretroviral therapy (ART)-naïve adults with acute HIV infection (AHI) in order to determine whether: * Administration of combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection (AHI) will be safe. * Participants who receive combination bNAb therapy in addition to ART during AHI will be more likely to demonstrate a delay in time to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks compared to participants who receive placebo plus ART. * Participants who receive combination bNAb therapy in addition to ART during AHI will demonstrate lower viral reservoirs and enhanced HIV-specific immunity compared to participants who receive placebo plus ART.

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.

What data supports the effectiveness of the drug combination of monoclonal antibodies and antiretroviral therapy for HIV infection?

The combination antiretroviral therapy (cART) has been shown to significantly reduce HIV replication and improve the quality of life for people living with HIV, although challenges like drug resistance and the need for new therapies remain. Monoclonal antibodies, as part of immunotherapy, are being explored to complement cART by targeting HIV-infected cells that cART alone may not fully address. ^{1 2 3 4 5}

Is the combination of monoclonal antibodies and antiretroviral therapy safe for humans?

Combination antiretroviral therapy (cART), also known as ART or HAART, has been effective in managing HIV but has had issues with long-term toxicity. Recent improvements have increased its safety, but some side effects like hypertension (high blood pressure) have been noted. Monoclonal antibodies like PGT121 and VRC07-523LS are newer treatments, and while specific safety data for these in combination with ART is limited, ongoing research aims to minimize risks. ^{2 3 6 7 8}

How is the Monoclonal Antibodies + ART treatment for HIV different from other treatments?

This treatment combines monoclonal antibodies with standard antiretroviral therapy (ART) to target HIV more effectively by not only suppressing the virus but also potentially reducing the reservoir of infected cells, which standard ART alone cannot achieve. ^{1 2 3 4 9}

Research Team

Trevor Crowell, MD, PhD

Principal Investigator

U.S. Military HIV Research Program CTU

Eligibility Criteria

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

I have received immunoglobulin therapy before.

Step 1: History of severe allergic reactions or chronic urticaria

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

Trial Timeline

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

Treatment Details

Interventions

• ART (Drug)
• PGT121.414.LS (Monoclonal Antibodies)
• Placebo (Other)
• VRC07-523LS (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Findings from Research

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]

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]

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]

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]

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]

References

1. Uganda 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. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Past HIV-1 Medications and the Current Status of Combined Antiretroviral Therapy Options for HIV-1 Patients. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Novel Antiretroviral Agents. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Immunotherapeutic restoration in HIV-infected individuals. [2011]

5. England pubmed.ncbi.nlm.nih.gov

Recent trends in early stage response to combination antiretroviral therapy in Australia. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Combination antiretroviral therapy. [2011]

7. England pubmed.ncbi.nlm.nih.gov

Determinants of survival following HIV-1 seroconversion after the introduction of HAART. [2019]

8. Uganda 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. [2022]

9. England 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. [2022]