New Study Highlights the Complexity of Using Antiviral Drug Combinations for HIV Prevention

MONROVIA, Calif., April 5, 2023 /PRNewswire/ — Researchers at the Oak Crest Institute of Science have been exploring new ways to prevent the spread of HIV-1 among adolescent girls and young women in low and middle income countries, who are disproportionately affected by HIV-1. One promising approach involves delivering antiviral compounds vaginally, using inserts, gels, films, or intravaginal rings. This method is appealing because it is women-controlled and topical, potentially reducing systemic exposure to the agents. However, a fundamental question remains: how many drugs are needed for an effective product, and are three drugs better than two? Some of these questions have been answered in a new study, and the answers may be surprising.

In a recent study using humanized mice (mice that have received implants of human cells and tissues so that they can be infected with HIV-1), researchers tested the vaginal HIV-1 prevention efficacy of single and combination antiviral compounds applied locally. They used a mathematical model to empirically study the effects of administering different doses of antiviral drugs. The results were unexpected: when tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) – both drugs that share the same mechanism of inhibiting HIV-1 reverse transcriptase thereby preventing viral replication in immune cells – were combined with a third drug that used a different mode of action against HIV-1, a strong antagonistic effect was observed. This means that the drugs were less effective when used together than they were when used separately. The TDF-FTC combination is FDA-approved as an oral regimen to prevent the acquisition of HIV-1.

The researchers were able to remedy the antagonistic effect by omitting TDF from the drug regimen. The management of HIV-1 in infected individuals using antiretroviral therapy relies on two or more drugs administered together to suppress the virus. It was hypothesized by many in the field that a similar paradigm would apply to HIV-1 prevention in healthy individuals. The results of this new study suggest that the approaches used in treatment may not be directly transferrable to HIV-1 prevention, especially in topical (i.e., vaginal) dosing.

This study provides a translational template for the preclinical evaluation of drug combinations for the prevention of HIV-1 and other viral diseases. Mice and humans have different physiology and microenvironments in their vaginal tissues, and those differences may limit the translational potential of these study results in humans. It is an important step forward in the development of safe, effective, and discreet HIV prevention products that can be controlled by women. The senior author on the report, Dr. Marc Baum at Oak Crest Institute of Science admits that the findings are “..going to be a bit controversial. The interaction between drugs that are effective when used alone but may interfere with each other when combined highlights the complexity of predicting the effects of drug use in HIV prevention. This serves as a reminder that more is not always better.”

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under Award Number U19AI113048. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Reference to paper

Humanized Mice

A humanized mouse is a type of laboratory mouse that has been genetically modified so that it has certain human characteristics. For this study, the mice were implanted with human immune cells and tissues so that they could be infected with HIV-1

Humanized mice are a powerful tool in biomedical research, helping scientists to better understand human biology and develop new treatments for diseases.

About Oak Crest Institute of Science

Founded in 1998, and celebrating its 25th anniversary in 2023, Oak Crest Institute of Science is a multi-disciplinary 501(c)(3) non-profit independent research organization located in Monrovia, California. The institute’s mission is to promote scientific research and education in the field of biomedical science through advanced research, education, and community outreach programs.

Oak Crest Institute of Science focuses on the discovery and development of novel drugs, vaccines, and diagnostic tools to address various global health challenges. The organization conducts research in areas such as infectious diseases, cancer, and neuroscience, and collaborates with other academic and research institutions, as well as pharmaceutical and biotech companies.

Oak Crest Institute of Science also offers training and education programs for students and professionals in the field of biomedical science, including undergraduate and graduate-level research internships and fellowships. Additionally, the organization is committed to community outreach and partners with local schools to provide educational opportunities for underserved students.

Paul Webster

SOURCE Oak Crest Institute of Science