Correlation between Human Immunodeficiency Virus Type 1 RNA Levels in the Female Genital Tract and Immune Activation Associated with Ulceration of the Cervix

• Published in: The Journal of infectious diseases 2000-06, Vol.181 (6), p.1950-1956
• Main Authors: Lawn, Stephen D., Subbarao, Shambavi, Wright, Thomas C., Evans-Strickfaden, Tammy, Ellerbrock, Tedd V., Lennox, Jeffrey L., Butera, Salvatore T., Hart, Clyde E.
• Format: Article
• Language: English
• Subjects: Adult; AIDS/HIV; Biological and medical sciences; Cytokines; Female; Genitalia; Genitalia, Female - virology; HIV; HIV 1; HIV-1 - genetics; HIV-1 - isolation & purification; HLA-DR Antigens - analysis; Human immunodeficiency virus 1; Human viral diseases; Humans; Infections; Infectious diseases; Interleukin-6 - analysis; Lesions; Lipopolysaccharide Receptors - analysis; Lymphocytes; Major Article; Medical sciences; Receptors, Interleukin-2 - analysis; RNA; RNA, Viral - analysis; shedding; Tumor Necrosis Factor-alpha - analysis; Ulcer - immunology; Ulcer - virology; Ulcers; Uterine Cervical Diseases - immunology; Uterine Cervical Diseases - virology; Uterine Cervical Dysplasia - therapy; Uterine Cervical Dysplasia - virology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315514

To address the hypothesis that local immune activation resulting from genital ulceration enhances human immunodeficiency virus type 1 (HIV-1) replication and shedding into the genital tract, paired plasma and cervicovaginal lavage (CVL) samples were obtained from 12 HIV-infected women before and after treatment of cervical intraepithelial lesions. Two weeks after treatment, inflammation and ulceration of the cervix were accompanied by major increases in mean concentrations of HIV-1 RNA (200-fold), tumor necrosis factor-α, interleukin 6, and soluble markers shed by activated lymphocytes and macrophages (sCD25 and sCD14, respectively) in CVL samples (P < .01 for each), but not plasma. Strong temporal and quantitative correlations were observed between concentrations of immunological markers and HIV-1 load in this compartment during a 10-week follow-up. Furthermore, in the presence of genital ulceration, HIV-1 in CVL samples was more readily captured by antibodies directed against virion-associated HLA-DR, a marker of host-cell activation, compared with virus in plasma. We suggest that local immune activation increases HIV-1 load in genital secretions, potentially increasing the risk of HIV-1 transmission.