Antibody‐Dependent Cell‐Mediated Cytotoxicity in Cervical Lavage Fluids of Human Immunodeficiency Virus Type 1–Infected Women (original) (raw)
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JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013
Objective-HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection -the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women. Methods-Data were obtained from HIV-infected and -uninfected female participants in the NA-ACCORD with no history of ICC at enrollment. Participants were followed from study entry or January, 1996 through ICC, loss-to follow-up or December, 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios (SIR). All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction. Results-A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years (pys) of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 pys, respectively). HIV-infected women with baseline CD4+ T-cells of ≥ 350, 200-349 and <200 cells/ uL had a 2.3-times, 3.0-times and 7.7-times increase in ICC incidence, respectively, compared with HIV-uninfected women (P trend =0.001). Of the 17 HIV-infected cases, medical records for the 5 years prior to diagnosis showed that 6 had no documented screening, 5 had screening with low grade or normal results, and 6 had high-grade results. Conclusions-This study found elevated incidence of ICC in HIV-infected compared touninfected women, and these rates increased with immunosuppression.
The Journal of Infectious Diseases, 2004
Antibodies that mediate human immunodeficiency virus (HIV)-specific antibody-dependent cell-mediated cytotoxicity (ADCC) are present in the cervical fluid of many HIV-positive women; however, the role that these antibodies play in host defense against HIV is not known. To understand the contribution of ADCC in cervical secretions as a protective mechanism against HIV, we evaluated ADCC titers in paired serum and cervical-lavage (CVL) samples from 1300 HIV-1-positive women who participated in the multicenter Division of AIDS Treatment Research Initiative Study 009. The present study demonstrates that women with CVL ADCC activity had lower genital viral loads than did women with serum ADCC activity only. Women with CVL ADCC activity were likely to have HIV-1 gp120-specific immunoglobulin (Ig) G, but not IgA, in their cervical fluid. This finding suggests that specific IgG in cervical fluid can mediate ADCC activity that inversely correlates with genital viral load. Antibody-dependent cell-mediated cytotoxicity (ADCC) combines acquired and innate immunity. The acquired response provides the antibodies; the effector cells are part of innate immunity. Innate ADCC effector cells include NK cells [1], monocytes and macrophages [2], polymorphonuclear leukocytes [3], and eosinophils [4]; they are not antigen specific, but they lyse infected cells after binding to the antibody's Fc region.