title: Risk of heterosexual HIV transmission attributable to sexually transmitted infections and non-specific genital inflammation in Zambian discordant couples, 1994-2012.
abstract: Studies have demonstrated the role of ulcerative and non-ulcerative sexually transmitted infections (STI) in HIV transmission/acquisition risk; less is understood about the role of non-specific inflammatory genital abnormalities.
  
  
  
  HIV-discordant heterosexual Zambian couples were enrolled into longitudinal follow-up (1994-2012). Multivariable models estimated the effect of genital ulcers and inflammation in both partners on time-to-HIV transmission within the couple. Population-attributable fractions (PAFs) were calculated.
  
  
  
  A total of 207 linked infections in women occurred over 2756 couple-years (7.5/100 CY) and 171 in men over 3216 CY (5.3/100 CY). Incident HIV among women was associated with a woman's non-STI genital inflammation (adjusted hazard ratio (aHR) = 1.55; PAF = 8%), bilateral inguinal adenopathy (BIA; aHR = 2.33; PAF = 8%), genital ulceration (aHR = 2.08; PAF = 7%) and the man's STI genital inflammation (aHR = 3.33; PAF = 5%), BIA (aHR = 3.35; PAF = 33%) and genital ulceration (aHR = 1.49; PAF = 9%). Infection among men was associated with a man's BIA (aHR = 4.11; PAF = 22%) and genital ulceration (aHR = 3.44; PAF = 15%) as well as with the woman's non-STI genital inflammation (aHR = 1.92; PAF = 13%) and BIA (aHR = 2.76; PAF = 14%). In HIV-M+F- couples, the man being uncircumcised. with foreskin smegma. was associated with the woman's seroconversion (aHR = 3.16) relative to being circumcised. In F+M- couples, uncircumcised men with BIA had an increased hazard of seroconversion (aHR = 13.03 with smegma and 4.95 without) relative to being circumcised. Self-reporting of symptoms was low for ulcerative and non-ulcerative STIs.
  
  
  
  Our findings confirm the role of STIs and highlight the contribution of non-specific genital inflammation to both male-to-female and female-to-male HIV transmission/acquisition risk. Studies are needed to characterize pathogenesis of non-specific inflammation including inguinal adenopathy. A better understanding of genital practices could inform interventions.
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Wall
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Kilembe
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|Departments of Gynecology and Obstetrics, Internal Medicine and Surgery, School of Medicine, University of Zambia, Lusaka, Zambia.
authors.forename: Bellington
authors.initials: B
authors.lastname: Vwalika
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|Department of Gynecology and Obstetrics, Emory University, School of Medicine, Atlanta, GA, USA.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Haddad
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|Departments of Gynecology and Obstetrics, Internal Medicine and Surgery, School of Medicine, University of Zambia, Lusaka, Zambia.
authors.forename: Shabir
authors.initials: S
authors.lastname: Lakhi
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|Departments of Gynecology and Obstetrics, Internal Medicine and Surgery, School of Medicine, University of Zambia, Lusaka, Zambia.
authors.forename: Roy
authors.initials: R
authors.lastname: Chavuma
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Naw
authors.initials: N
authors.lastname: Htee Khu
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|Department of Epidemiology, Ryals School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Ilene
authors.initials: I
authors.lastname: Brill
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Cheswa
authors.initials: C
authors.lastname: Vwalika
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Mwananyanda
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|Ministry of Community Development, Mother and Child Health, Lusaka, Zambia.
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Tichacek
authors.affiliation: Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
mesh_terms: D000328:Adult; D017280:Condoms / Q000706:statistics & numerical data; D005191:Family Characteristics; D005260:Female; D005835:Genitalia / Q000473:pathology*; D015658:HIV Infections / Q000453:epidemiology* / Q000635:transmission*; D020010:Heterosexuality; D006801:Humans; D007249:Inflammation / Q000150:complications; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D012307:Risk Factors; D015024:Zambia / Q000453:epidemiology
keywords: Couples’; HIV risk; Zambia; discordant couples; genital ulceration and inflammation; longitudinal cohort; voluntary HIV counselling and testing