title: Relationship Between Genital Drug Concentrations and Cervical Cellular Immune Activation and Reconstitution in HIV-1-Infected Women on a Raltegravir Versus a Boosted Atazanavir Regimen.
abstract: Determinants of HIV-infected women's genital tract mucosal immune health are not well understood. Because raltegravir (RAL) achieves relatively higher genital tract concentrations than ritonavir-boosted atazanavir (ATV), we examined whether an RAL-based regimen is associated with improved cervical immune reconstitution and less activation in HIV(+) women compared to an ATV-based regimen. Peripheral blood, cervical brushings, cervical-vaginal lavage (CVL), and cervical biopsies were collected from HIV(+) women on tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and either RAL (n=14) or ATV (n=19) with CD4(+) T cells>300 cells/mm(3) and HIV RNA<48 copies/ml. HLA-DR(+)CD38(+) T cells were measured in blood and cervical cells using flow cytometry, CD4(+) and CD8(+) T cells were quantified in cervical biopsies by immunofluorescent analysis, and HIV RNA (VL), ATV, and RAL concentrations were measured in CVL. In a linear regression model of log(CVL concentration) versus both log(plasma concentration) and treatment group, the RAL CVL level was 519% (95% CI: 133, 1,525%) higher than for ATV (p<0.001). Genital tract VL was undetectable in 90% of subjects and did not differ by regimen. There were no significant differences between groups in terms of cervical %HLA-DR(+)CD38(+)CD4(+) or CD8(+) T cells, CD4(+) or CD8(+) T cells/mm(2), or CD4:CD8 ratio. After adjusting for treatment time and group, the CVL:plasma drug ratio was not associated with the cervical CD4:CD8 ratio or immune activation (p>0.6). Despite significantly higher genital tract penetration of RAL compared to ATV, there were no significant differences in cervical immune activation or reconstitution between women on these regimens, suggesting both drug regimens achieve adequate genital tract levels to suppress virus replication.
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Amie L
authors.initials: AL
authors.lastname: Meditz
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Claire
authors.initials: C
authors.lastname: Palmer
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Julie
authors.initials: J
authors.lastname: Predhomme
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Kristina
authors.initials: K
authors.lastname: Searls
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Becky
authors.initials: B
authors.lastname: Kerr
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Sharon
authors.initials: S
authors.lastname: Seifert
authors.affiliation: 2 Denver Public Health , Denver, Colorado.
authors.forename: Patricia
authors.initials: P
authors.lastname: Caraway
authors.affiliation: 1 University of Colorado , Aurora, Colorado.|2 Denver Public Health , Denver, Colorado.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Gardner
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Samantha
authors.initials: S
authors.lastname: MaWhinney
authors.affiliation: 1 University of Colorado , Aurora, Colorado.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000069446:Atazanavir Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001769:Blood / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D005260:Female; D005836:Genitalia, Female / Q000737:chemistry* / Q000473:pathology*; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate