Relationship between HIV viral load and Langerhans cells of the cervical epithelium

Abstract

To determine the relationship between the density of cervical mucosa Langerhans cells, cervical histology, and HIV viral load. Eighty-four HIV-infected and 17 women at high risk for HIV had cervical biopsies assessed for squamous intraepithelial lesions and Langerhans cell density. Langerhans cells were identified using the S-100 immunohistochemical stain and were counted manually. Polymerase chain reaction assays were used to detect cervical human papillomavirus (HPV)-DNA. T-cell subsets were determined using immunofluorescent flow cytometry. Plasma HIV RNA levels were measured using a nucleic acid sequence-based amplification technique. The associations between cervical Langerhans cell density, cervical histology, CD4 counts, HIV viral loads, HPV-DNA detection, and smoking status were assessed using multivariate statistical models. In multivariate analysis among women infected with HIV, the mean Langerhans cell density per high-powered field was 4.00 among women with no detectable plasma HIV-RNA, and 1.92 among those with detectable HIV-RNA (P = 0.01). The mean cervical Langerhans cell density was increased in women with high-grade squamous intraepithelial lesions compared with those with low-grade squamous intraepithelial lesions and normal/metaplastic histology (3.87 vs 2.11; P = 0.05). Neither HPV-DNA detection, smoking status, nor CD4 count was significantly associated with Langerhans cell density. The decrease in cervical Langerhans cell density in women with detectable HIV-RNA suggests an impaired mucosal immune response to local infections, such as HPV. Conversely, HPV infection resulting in high-grade dysplasia might be associated with an enhanced local immune response.