MCAT Biological and Biochemical Foundations of Living Systems: Passage 18 — Flashcards

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HIV type 1 is one of several sexually transmitted infections, along with human papillomavirus and herpes simplex virus 2, that disproportionately affects women. Young women are an especially vulnerable population and represent more than 25% of new infections. In sub-Saharan Africa, which is the epicenter of the global HIV epidemic, women account for approximately 60% of people living with HIV. In addition to gender inequalities, there are biological factors that put women at a higher risk of being infected with HIV and change the course of disease, including anatomical and hormonal differences and X and Y chromosome–linked genes. \

Women actually have lower viral load and higher CD4+ T-cell count than men in both acute and chronic infection; however, despite these factors, women experience faster disease progression and are more likely than men to develop AIDS. One of the major determinants of disease progression is immune activation. Plasmacytoid dendritic cells (pDCs) detect HIV-1 RNA via cell-surface molecules called Toll-like receptors (TLRs), of which there are about a dozen types in mammals. TLR-3, -7, and -8 recognize molecular patterns in RNA viruses, whereas TLR-4, -5, and -9 generally recognize ligands present in bacteria.

In response, pDCs produce interferon-α (IFN-α), an antiviral cytokine molecule. Studies have reported that pDCs derived from women produce more IFN-α following exposure to HIV-1 than cells from men. Furthermore, one study found that a type of estrogen hormone, called 17-beta-estradiol, could boost the response of pDCs to HIV-1 exposure, which in turn could help mount a stronger immune response.

The superior immune activation could, however, lead to a larger burden of non–AIDS-related disease, such as premature aging, in HIV-infected women, compared with men. Studies based on large health registries suggest that the increased risk of myocardial infarction associated with HIV-1 infection is greater for women than it is for men.

More generally, sex-based differences in immune stimulation and the interferon-alpha response could put women at higher risk of various chronic and autoimmune diseases. Treatment with antiretroviral therapy (ART) appears to benefit women and men equally, although there are gender and racial differences in likelihood of starting ART. In addition, there are sex-based differences in the frequency of adverse events associated with ART, with women being at higher risk of developing nausea, skin rash, and other problems, while men are more likely to experience nausea and sleep difficulties.