Elevated Cervical White Blood Cell Infiltrate Is Associated with Genital HIV Detection in a Longitudinal Cohort of Antiretroviral Therapy-Adherent Women

Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 10/2010; 202(10):1543-52. DOI: 10.1086/656720
Source: PubMed


Identification of factors associated with the presence of human immunodeficiency virus (HIV) in female genital secretions is critical for intervention strategies targeting transmission and eliminating replication of genital virus. We sought to monitor the prevalence of genital HIV shedding in antiretroviral therapy-adherent women over time and to assess changes in the genital microenvironment.
Levels of cell-free HIV (HIV RNA) and HIV-infected cells (HIV DNA) were monitored in peripheral blood samples and cervical and vaginal fluid samples at monthly intervals in 11 women for 1 year. Genital tract infections and fluctuations in cervical and vaginal white blood cell counts were also evaluated at each study visit.
Plasma HIV was undetectable at the majority of study visits; when detected, it was only at low levels. Throughout the study, genital HIV RNA and DNA were detected in each person. Combined genital HIV (RNA and DNA) was detected at 49.2% of study visits and was associated with an elevated concentration of cervical white blood cell infiltrate (odds ratio, 2.52 [95% confidence interval, 1.01-6.22]; P = .04). Infiltrate was not associated with a clinical disorder or patient-reported symptoms.
Despite antiretroviral therapy adherence and clinically suppressed plasma viremia, HIV was intermittently detected in genital secretions and was associated with subclinical inflammation and cells trafficking to the cervical mucosa.

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    • "The presence of HIV tat and gp120 in the mucosal environment of HIV-infected individuals is critical for the disruption of epithelial junctions and the exposure of nectin-1. The presence of HIV virions and HIV gene products in oral and genital epithelium is well described [15], [106], [107], [108], [109], [110], [111], [112], [113], [114], [115], [116], [117], [118], [119], especially in circulating HIV-infected immune cells [117], [118], [119]. Secretion of HIV tat and gp120 into blood has been shown [54], [55], [56], [57], [120], [121], [122]. "
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    • "HIV-infected lymphocytes, and Langerhans cells can be detected in the mucosal and submucosal layers of oral and genital epithelium (Chou et al., 2000; Jayakumar et al., 2005; Qureshi et al., 1995, 1997; Rodriguez-Inigo et al., 2005), and HIV virions can be detected by electron microscopy, within the TJs of oral epithelium (Qureshi et al., 1997). Finally, replicating HIV and HIV-infected cells have been found within cervical epithelia of HIV-infected women, including women on ART (Crowe and Sonza, 2000; Henning et al., 2010; Sonza et al., 2001). "
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