Monoclonal Antibodies Reveal Promise for Viral Suppression Failure

By: Ranier Simons, ADAP Blog Guest Contributor

There are multiple treatment goals of HIV antiretroviral therapy (ART): “maximally and durably suppress plasma HIV RNA, restore and preserve immunologic function, reduce HIV-associated morbidity and prolong the duration and quality of survival, and prevent HIV transmission.”[1] Suppressing the HIV viral load to an undetectable status means reducing the levels of HIV in the blood so low that it cannot be detectable by blood assay tests. Usually, after starting ART, patients achieve viral suppression after 12-24 weeks of therapy.[1]

However, viral suppression is sometimes not maintained or achieved at all. Virological suppression failure happens in patients who initially contract drug-resistant strains of HIV, patients who have inadequate adherence to treatment regimens, those who acquire resistance over time after long-term treatment, and by nature of the pharmacokinetics and pharmacodynamics of the drugs in some patients’ bodies based on their genetics.[2] ART consists of drug cocktails of antiretroviral medications. Advancements in HIV research have resulted in many different ART medicines for patients. Thus, patients have other options to switch to when one regimen is unsuccessful. 

Unfortunately, there are patients who have exhausted many available avenues of therapy without achieving viral suppression. Ongoing research is looking into means by which to augment the current library of drug options as well as create new drugs. A recent study presented in May at the 2023 American Conference for the Treatment of HIV™ (ACTHIV™) is a promising development. ACTHIV™ is a conference dedicated to those on the frontline of treating HIV patients. The conference presents research and developments that can be directly integrated into the clinical setting.[3] 

Photo Source: New England AETC

The study involved the use of monoclonal antibodies as part of ART. Monoclonal antibodies are proteins synthesized in a lab that act like the antibodies we already produce. The monoclonal antibodies stimulate your immune system by binding to foreign invaders, such as viruses, to help your body attack them.[4] The subject of the study was a monoclonal antibody called ibalizumab, marketed by Theratechnologies as Trogarzo. Trogarzo is a long-acting, CD4-directed, post-attachment HIV-1 inhibitor.[5] The FDA initially approved it in 2018 for treating adults with multi-drug resistant HIV with unsuccessful ART regimens.

This study was novel because it was the first one directly comparing ibalizumab with non-ibalizumab regimens. The clinical trials cohort data was compared to real-world population data of appropriately matched patients on non-ibalizumab-containing regimens. The non-ibalizumab control group was taken from a database called OPERA, an extensive electronic health record database with deidentified patient-level data encompassing around 14% of the total United States' HIV population collected at the point of care.[6] Results from 76 ibalizumab-treated patients from clinical trials were compared to 65 comparable non-ibalizumab-regimen patients from OPERA. 

Photo Source: POZ

Using ibalizumab sped up the time period to viral suppression compared to the control group. The data showed a doubling in the likelihood of viral suppression compared to the non-ibalizumab group.[6] Additionally, viral suppression was more robust. About 95% of the ibalizumab group stayed undetectable through the completion of the study, compared to 27% of those who achieved undetectable status without ibalizumab. The odds of losing viral suppression were 16 to 18 times higher in those in the non-ibalizumab group.[6] The most remarkable aspect of the results is that those in the ibalizumab group had more severe disease progression at the start of the study than those in the control group.[5] Yet they still had better outcomes.

The study solidified the clinical efficacy of using ibalizumab. This is promising because it legitimizes a pathway to develop similar ART tools in the future. It also proves the effectiveness of using databases like OPERA to comparatively study present and future innovations.

[1] NIH Office of AIDS Research. (2016, January 28). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Retrieved from https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/treatment-goals

[2] Bessong, P.O., Matume, N.D. & Tebit, D.M. Potential challenges to sustained viral load suppression in the HIV treatment programme in South Africa: a narrative overview. AIDS Res Ther 18, 1 (2021). https://doi.org/10.1186/s12981-020-00324-w

[3] American Conference for the Treatment of HIV. (2023). https://acthiv.org/

[4] Cleveland Clinic. (2023). Monoclonal Antibodies. Retrieved from https://my.clevelandclinic.org/health/treatments/22246-monoclonal-antibodies

[5] Theratechnologies. (2023, May 4). Theratechnologies’ Trogarzo® (Ibalizumab-uiyk) Shortens Time to HIV Undetectability and Extends Durability of Undetectability and Viral Suppression in a Matched Treatment Comparison. Retrieved from https://www.theratech.com/news-releases/news-release-details/theratechnologies-trogarzor-ibalizumab-uiyk-shortens-time-hiv

[6] Feller, S. (2023, May 13). Monoclonal antibody speeds time to HIV viral suppression, study finds. Retrieved from https://www.healio.com/news/infectious-disease/20230512/monoclonal-antibody-speeds-time-to-hiv-viral-suppression-study-finds?utm_medium=social&utm_source=twitter&utm_campaign=sociallinks

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.