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Mucosal tenofovir 1% gel stimulates cell proliferation and type I/III interferon pathways
Sean M Hughes1, Fernanda L Calienes1, Claire N Levy1
1Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, USA.
Tenofovir gel and oral pre-exposure prophylaxis (PrEP) induce type I/III interferon genes in the mucosa. This persistent immune response may impact HIV treatment and chronic disease risk.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Oral tenofovir is a crucial antiretroviral for HIV treatment and pre-exposure prophylaxis (PrEP).
- Topical tenofovir gel has been investigated for vaginal and rectal PrEP, with initial studies showing gene expression changes in rectal tissue.
Purpose of the Study:
- To investigate the duration and persistence of tenofovir's effects on gene expression in mucosal tissues.
- To compare the effects of topical tenofovir gel and oral tenofovir on gene expression in rectal and vaginal tissues.
- To identify consistent mucosal responses to tenofovir across different delivery methods and durations.
Main Methods:
- Analysis of transcriptomes and proteomes from tissue samples collected before and after daily topical tenofovir 1% gel application.
- Data from three clinical trials (MTN-014 and MTN-017) involving rectal and vaginal tissues with treatment durations of 14 and 56 days.
- Comparison of gene expression changes induced by topical tenofovir gel with known effects of oral PrEP.
Main Results:
- Many gene expression changes observed after 7 days of tenofovir gel diminished by 14 and 56 days.
- Persistent increases in cell proliferation and type I/III interferon-related genes were noted.
- Topical vaginal gel uniquely induced changes associated with epithelial-mesenchymal transition and angiogenesis.
- Induction of type I/III interferon-related genes was the most consistent and persistent mucosal response to tenofovir, observed with both oral and topical administration.
Conclusions:
- The induction of type I/III interferon-related genes is a consistent mucosal response to tenofovir, regardless of administration route or duration.
- While interferon induction might enhance antiviral efficacy, it could also contribute to comorbidities in people living with HIV.
- This immunological effect warrants consideration in long-term HIV management and the development of HIV cure interventions.
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