Higher colorectal tissue HIV infectivity in cisgender women compared with MSM before and during oral preexposure prophylaxis

AIDS, April 2021.

Study A5305/17 was a mucosal tissue-focused sub-study of HPTN 069/ACTG 5305. The objectives were to compare medication levels in different body tissues (cervix and colorectal tissues) and blood in HIV-negative cisgender women and men who have sex with men (MSM) who are taking oral PrEP. In addition, colon cells were checked to see how susceptible they may be to HIV infection (outside the body, or ex-vivo). Samples were collected at baseline (before receiving PrEP), at week 24 and 48 (on PrEP), and at week 49 (one-week after discontinuing PrEP). The study measured the degree of HIV infectivity in colon tissue biopsies challenged ex vivo with HIV, followed by HIV p24 measurement.

The study demonstrated a substantial two- to 16-fold increase in susceptibility of colorectal tissue to HIV infection in cisgender women compared to MSM. Differences in adherence, drug concentration, and colorectal tissue flow cytometry do not explain these findings well. Additional research is necessary to understand this increased susceptibility.

These findings complement behavioral and prior pharmacokinetic data in cisgender women. The data may also provide additional explanations for the high level of population risk of receptive anal sex for HIV acquisition among cisgender women, and the differences in oral tenofovir/emtricitabine adherence required to achieve the highest levels of PrEP protection.

Summary and Clinical Implications: A number of studies suggest that oral PrEP does not work as well for cisgender women as for other populations. This study shows us that specific tissues are more likely to be infected with HIV in cisgender women, meaning that oral PrEP may not protect them as well as MSM. We need to know why and develop better PrEP options for cisgender women.

Sekabira, R., Mcgowan, I., Yuhas, K., Brand, R. M., Marzinke, M. A., Manabe, Y. C., Frank, I., Eron, J., Landovitz, R. J., Anton, P., Cranston, R. D., Anderson, P., Mayer, K. H., Amico, K. R., Wilkin, T. J., Chege, W., Kekitiinwa, R., Mccauley, M., Gulick, R. M., & Hendrix, C. W. (2021). Higher colorectal tissue HIV infectivity in cisgender women compared with MSM before and during oral preexposure prophylaxisAIDS (London, England), 10.1097/QAD.0000000000002907. Advance online publication. https://doi.org/10.1097/QAD.0000000000002907