title: Innate immune activation enhances hiv acquisition in women, diminishing the effectiveness of tenofovir microbicide gel.
abstract: The antiretroviral agent, tenofovir, formulated as a vaginal microbicide gel, reduces human immunodeficiency virus (HIV) acquisition by 39% in women. This study assessed the role of preexisting immune activation in HIV acquisition in women from the CAPRISA 004 trial, to identify potential strategies to increase the effectiveness of tenofovir gel. Systemic cytokine and cellular immune mediators (platelets and natural killer [NK] cells) were assessed in women at high risk for HIV assigned to either tenofovir or placebo gel in the CAPRISA 004 trial. Notwithstanding tenofovir gel use, women who acquired HIV had significantly higher systemic innate immune activation prior to infection than women who remained uninfected. Activation of both soluble (cytokine) and cellular (NK cells) immune mediators were associated with HIV acquisition, individually or in combination. Hence, an innate immune activation suppressant could be added to tenofovir gel as a potential combination gel strategy in developing the next generation of higher efficacy antiretroviral microbicides.
authors: CAPRISA - Centre for the AIDS Programme of Research in South Africa.
authors: Vivek
authors: V
authors: Naranbhai
authors: Salim S
authors: SS
authors: Abdool Karim
authors: Marcus
authors: M
authors: Altfeld
authors: Natasha
authors: N
authors: Samsunder
authors: Raveshni
authors: R
authors: Durgiah
authors: Sengeziwe
authors: S
authors: Sibeko
authors: Quarraisha
authors: Q
authors: Abdool Karim
authors: William H
authors: WH
authors: Carr
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D030161:Avian Proteins / Q000097:blood; D016022:Case-Control Studies; D060085:Coinfection; D016207:Cytokines / Q000097:blood; D004198:Disease Susceptibility / Q000097:blood / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D006558:Herpes Genitalis / Q000276:immunology / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016015:Logistic Models; D008213:Lymphocyte Activation; D063065:Organophosphonates / Q000627:therapeutic use*; D010976:Platelet Count; D025341:Principal Component Analysis; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D000068698:Tenofovir; D014622:Vaginal Creams, Foams, and Jellies / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D030161:Avian Proteins; D016207:Cytokines; C071280:EMF-1 protein, Gallus gallus; D063065:Organophosphonates; D014622:Vaginal Creams, Foams, and Jellies; D000068698:Tenofovir; D000225:Adenine