NIAID Explores New HIV Cure Approaches Using Broadly Neutralizing Antibodies

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NIAID Explores New HIV Cure Approaches Using Broadly Neutralizing Antibodies

NIAID Explores New HIV Cure Approaches Using Broadly Neutralizing Antibodies

A recent article highlights ongoing clinical trials by the National Institute of Allergy and Infectious Diseases (NIAID) and its collaborators.

These trials aim to control or eradicate HIV using broadly neutralizing antibodies (bNAbs).

The goal is to develop a method that allows people with HIV to maintain low levels of the virus or even eliminate it without the need for long-term antiretroviral therapy (ART), potentially leading to a cure.

NIAID Explores New HIV Cure Approaches Using Broadly Neutralizing Antibodies

The Role of Broadly Neutralizing Antibodies

ART has significantly impacted HIV management, but the virus can quickly rebound once treatment is stopped. Therefore, NIAID and its partners are exploring strategies to either eradicate HIV from the body or control it to a level where the immune system can keep it in check.

Many potential HIV cure strategies focus on bNAbs, which can neutralize various HIV strains by targeting specific viral components and triggering an immune response to destroy the virus. Several bNAbs have been developed and tested to determine their effectiveness in preventing or treating HIV.

NIAID and its collaborators are conducting clinical trials globally, including in Africa, North America, South America, and Southeast Asia, to assess the efficacy of these bNAbs-based HIV eradication strategies, either alone or in combination with other immune-boosting tactics.

Challenges in Finding an HIV Cure

Developing an HIV cure is complex due to the virus’s ability to hide in certain tissues or cells, evading the immune system. Even individuals with undetectable viral loads may experience a resurgence of the virus after stopping treatment, as the previously hidden virus begins to replicate again.

This issue is particularly pressing in resource-limited areas, where access to consistent HIV treatment may be lacking. A short-term therapy that could prevent viral replication long-term or completely eradicate the virus would significantly improve the quality of life for people living with HIV and reduce the risk of transmission.

Clinical Trials in Africa

Two studies launched this summer are evaluating the potential of bNAbs to achieve HIV remission in infected individuals in Africa. These studies will closely monitor ART interruption to assess whether bNAbs can control HIV over the long term without the need for ART.

The “Pause and Structured ART Interruption Evaluation” (PAUSE) trial, which began recruiting participants in June 2024, is enrolling HIV-positive individuals in Botswana, Malawi, and South Africa. Participants who have achieved viral suppression through ART will receive two long-acting bNAbs, 3BNC117-LS-J and 10-1074-LS-J, before pausing ART to see if these bNAbs can control HIV in the absence of ART.

Another study, “Antiretroviral and Antibody Combination in African HIV-1 Cure Trials” (ACACIA), is set to begin and will study bNAbs 3BNC117-LS (also known as teropavimab) and 10-1074-LS (also known as zinlirvimab) in HIV-positive individuals in Botswana, Malawi, South Africa, and Zimbabwe. Participants will receive these bNAbs early in their ART treatment to see if they enhance the immune response against HIV and reduce the viral reservoir. Once the bNAbs are depleted, ART will be interrupted, and researchers will assess how long participants can maintain viral suppression without ART.

Exploring HIV Cure Strategies for Children

Researchers are also studying bNAb-based HIV cure strategies in children through the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT). The IMPAACT P1115 study has explored very early HIV treatment strategies in infants exposed to or infected with HIV before birth.

This study evaluated the bNAbs VRC01 and VRC07-523LS to determine if combining these antibodies with early ART could help children achieve HIV remission without long-term ART.

Another study, IMPAACT 2042, is evaluating three bNAbs—VRC07-523LS, PGDM1400LS, and PGT121.414.LS—in HIV-positive children and adolescents aged 2 to 25 years to see if they can be part of a strategy to suppress HIV and eradicate the virus from the body.

Combining bNAbs and Vaccines

Additional clinical studies are combining bNAbs with therapeutic vaccines to achieve HIV eradication. These vaccines aim to enhance the immune response to the virus in people living with HIV.

The ACTG A5374 study, which began enrolling participants in early 2024, is evaluating the safety of combining the bNAbs teropavimab and zinlirvimab with the therapeutic vaccines ChAdOx1.HIV cons1/62 and MVA.HIV cons3/4, along with an immune booster, vesatolimod. This trial, conducted in the United States and Brazil, aims to see if this combination can eliminate HIV-infected cells and prevent the reactivation of the viral reservoir during ART interruption.

The outcomes of these and related trials will provide researchers with new insights into more effective HIV treatments or potential cures. This research leverages the strengths of all NIH-funded HIV clinical trial networks and partner organizations.

The Bill & Melinda Gates Foundation has co-funded the PAUSE and ACACIA trials, while the IMPAACT P1115 and 2042 studies are co-funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, a part of NIH.

Ongoing NIAID Projects

Broadly neutralizing antibodies VRC01 and VRC07-523LS were developed by NIAID’s Vaccine Research Center and intramural research division.

The bNAbs 3BNC117 and 10-1074 were discovered by researchers at Rockefeller University, with partial funding from NIAID.

PGT121.414.LS and PGDM1400LS are currently under development by NIAID and its partners.

Further Information on Trials:

ACTG A5374: ClinicalTrials.gov ID NCT067071767.
ACTG A5416 (PAUSE): ClinicalTrials.gov ID NCT06031272.
ACTG A5417 (ACACIA): ClinicalTrials.gov ID NCT06205602.
IMPAACT P1115: ClinicalTrials.gov ID NCT02140255. (Recent findings from P1115 were presented at the 2024 Conference on Retroviruses and Opportunistic Infections.)
IMPAACT 2042 (Tatelo Plus): ClinicalTrials.gov ID to be announced.