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

Aim: To determine the relationship between the density of cervical mucosa Langerhans cells, cervical histology, and HIV viral load. Methods: 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. Results: 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. Conclusions: 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.