title: Daily oral emtricitabine/tenofovir preexposure prophylaxis and herpes simplex virus type 2 among men who have sex with men.
abstract: BACKGROUND
  In addition to protecting against HIV acquisition, antiretroviral preexposure prophylaxis (PrEP) using topical 1% tenofovir gel reduced Herpes simplex virus type 2 (HSV-2) acquisition by 51% among women in the CAPRISA 004 study. We examined the effect of daily oral emtricitabine/tenofovir (FTC/TDF) PrEP on HSV-2 seroincidence and ulcer occurrence among men who have sex with men (MSM) in the iPrEx trial.
  
  
  METHODS
  HSV-2 serum testing was performed at screening and every six months. Among HSV-2-seronegative individuals, we used Cox regression models to estimate hazard ratios (HRs) of HSV-2 seroincidence associated with randomization to FTC/TDF. We used multiple imputation and Cox regression to estimate HRs for HSV-2 seroincidence accounting for drug exposure. We assessed ulcer occurrence among participants with prevalent or incident HSV-2 infection.
  
  
  RESULTS
  Of the 2,499 participants, 1383 (55.3%) tested HSV-2-seronegative at baseline, 892 (35.7%) tested positive, 223 (8.9%) had indeterminate tests, and one test was not done. Of the 1,347 HSV-2-seronegative participants with follow-up, 125 (9.3%) had incident HSV-2 infection (5.9 per 100 person-years). Compared with participants receiving placebo, there was no difference in HSV-2 seroincidence among participants receiving FTC/TDF (HR 1.1, 95% CI: 0.8-1.5; P = 0.64) or among participants receiving FTC/TDF with a concentration of tenofovir diphosphate >16 per million viable cells (HR 1.0, 95% CI: 0.3-3.5; P = 0.95). Among participants with HSV-2 infection, the proportion with ≥1 moderate or severe ulcer adverse event was twice as high in the placebo vs. active arm (5.9% vs. 2.9%, P = 0.02), but there were no differences in the proportions with ≥1 clinical examination during which perianal or groin ulcers were identified.
  
  
  CONCLUSIONS
  Tenofovir in daily oral FTC/TDF PrEP may reduce the occurrence of ulcers in individuals with HSV-2 infection but does not protect against HSV-2 incidence among MSM.
authors.affiliation: Gladstone Institute of Virology and Immunology, San Francisco, California, United States or America; University of California, Berkeley, California, United States of America.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Marcus
authors.affiliation: University of California San Francisco, San Francisco, California, United States of America.
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.affiliation: Gladstone Institute of Virology and Immunology, San Francisco, California, United States or America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: McMahan
authors.affiliation: Asociación Civil Impacta Salud y Educación, Lima, Peru.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Lama
authors.affiliation: Fenway Institute, Fenway Health, Boston, Massachusetts, United States of America; Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.affiliation: Bridge HIV, San Francisco Department of Public Health, San Francisco, California, United States of America.
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Liu
authors.affiliation: Fundación Ecuatoriana Equidad, Guayaquil, Guayas, Ecuador.
authors.forename: Orlando
authors.initials: O
authors.lastname: Montoya-Herrera
authors.affiliation: Asociación Civil Selva Amazónica, Iquitos, Peru.
authors.forename: Martin
authors.initials: M
authors.lastname: Casapia
authors.affiliation: Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Brenda
authors.initials: B
authors.lastname: Hoagland
authors.affiliation: Gladstone Institute of Virology and Immunology, San Francisco, California, United States or America; University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D018890:Chemoprevention; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068679:Emtricitabine; D006561:Herpes Simplex / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000145:classification / Q000187:drug effects*; D018451:Homosexuality, Male; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D015995:Prevalence; D012307:Risk Factors; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine