Do Sex Differences Matter for HIV Cure?
By Jeffrey Laurence, M.D.
Persistent infection—some latent, some active to varying extents—is the primary obstacle to curing HIV. Differences among infected cell types and other factors specific to different tissue reservoirs could influence the efficacy of a given cure strategy. In addition, sex-specific differences are known to affect many aspects of HIV infection, but there is limited information about variations in HIV reservoir size and activity in different tissues in women.
Study lead author Dr. Steve YuklBlood and biopsies from different parts of the intestinal and genital tracts of six cisgender women on effective antiretroviral therapy were examined using highly sensitive techniques to assess relative levels of HIV DNA and different forms of HIV RNA that reflect the level of reservoir activity.
Total HIV provirus—virus interwoven into host DNA—was greater in the intestines and outer cervix than in blood or the lining of the uterus. Active HIV signals, quantitated on an RNA per proviral DNA basis, were higher in the rectum than other parts of the intestines, and higher in the lining of the uterus than in any other tissues sampled. These levels were comparable to those found in blood. This held true even when adjusting for the fact that the uterine lining has a lot of blood vessels, and therefore holds a lot of blood.
The finding of a greater number of HIV-infected cells in the intestines than in the blood of these women paralleled earlier findings for cisgender men. There was a distinction between different sections of the intestines, however, with more virus expressed in the rectum than other parts of the intestines in women, and the reverse in men.
The authors conclude that “Therapies aimed at disrupting latency will be required to penetrate into multiple tissues and target different blocks” to HIV growth, the extent of which may differ in men and women.
amfAR was a funder of this research.
Dr. Laurence is amfAR’s senior scientific consultant.