Over the years, an array of theories have been offered to explain the increased risk of heterosexual HIV transmission in sub-Saharan Africa compared to the US and Europe. But these theories have almost exclusively focused on behavior, not biology. An example is the claim that concurrent sexual relationships are more common and account for higher HIV prevalence, which has achieved some popularity despite a lack of evidence to support it. Only a few studies have documented that background levels of immune activation are higher in sub-Saharan Africa, and suggested that this could contribute to an increased HIV transmission risk. And up until now, no research has specifically looked at immune activation in the genital tract.
A new paper by Craig Cohen and colleagues, just published in the journal AIDS, addresses this information gap. The authors start by noting that mucosal immune activation caused by genital tract infections (such as HSV-2) has been consistently associated with an increased risk of HIV acquisition. To address whether there might be geographic differences in background levels of immune activation in healthy women without any active infections, cervical samples from 18 women in San Francisco and 36 women in Kisumu were compared. Although the total number of CD4 cells in the samples were slightly higher in women from San Francisco, the number and proportion of activated CD4 T cells was significantly higher in the women from Kisumu (p value=<0.0001). Similar results were obtained when activated CD8 T cells were analyzed. The findings held true after controlling for multiple factors, including HPV status.
The authors conclude by stating: “Although other factors such as physical, behavioral, and structural conditions certainly put young women in sub-Saharan African at greater risk of HIV acquisition, ours is the ﬁrst study to demonstrate that mucosal immune differences in the genital tract may also be important. In addition to stimulating further research, we believe that these ﬁndings should also start to dispel some of the preconceptions and stigma surrounding HIV acquisition among young women in sub-Saharan Africa.”
AIDS. 2010 Jun 25. [Epub ahead of print]
Cohen CR, Moscicki AB, Scott ME, Ma Y, Shiboski S, Bukusi E, Daud I, Rebbapragada A, Brown J, Kaul R.
aDepartment of Obstetrics, Gynecology and Reproductive Sciences, USA bDepartment of Pediatrics, USA cDepartment of Biostatistics, University of California, San Francisco, California, USA dCenter for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya eDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada fDepartment of Epidemiology University of California, Los Angeles, California, USA.
OBJECTIVES: To determine whether healthy, young women in sub-Saharan Africa have a more activated immune milieu in the genital tract (i.e. activated CD4 T cells) than a similar population in the United States. DESIGN:: A cross-sectional study nested in a phase 1 microbicide trial. METHODS: Cervical cytobrushes were collected from 18 to 24-year-old women in San Francisco, California, USA (n = 18) and Kisumu, Kenya (n = 36) at enrollment into a phase 1 microbicide trial. All participants tested negative for HIV, herpes simplex virus 2, gonorrhea, chlamydia, and trichomonas, and had abstained from sex for at least 7 days prior to enrollment. Cryopreserved T-cell populations were assayed by flow cytometry in a central laboratory. Secretory leukocyte protease inhibitor levels were assayed in cervicovaginal lavage samples. The Wilcoxon rank-sum test was used to compare immune parameters between sites. RESULTS: The total number of endocervical CD4 T cells was slightly higher in participants from San Francisco, but participants from Kisumu had a substantially higher number and proportion of CD4 T cells expressing the early activation marker CD69, with and without the HIV coreceptor C-C chemokine receptor type 5, and a greater proportion of activated CD8 T cells. Median (interquartile range) genital levels of secretory leukocyte protease inhibitor were lower in participants from Kisumu compared with those from San Francisco [190 (96-519) vs. 474 (206 817) pg/ml, P < 0.03]. CONCLUSION: Activated mucosal T cells were increased in the genital tract of young, sexually transmitted infection/HIV-free Kenyan women, independent of common genital coinfections, and secretory leukocyte protease inhibitor levels were reduced. The cause of these mucosal immune differences is not known, but could partly explain the high HIV incidence in young women from sub-Saharan Africa.