title: Biological factors that place women at risk for HIV: evidence from a large-scale clinical trial in Durban.
abstract: BACKGROUND
  It is well documented that the mucosal linings of the female genital tract (FGT) usually provides a robust barrier that protects against sexually acquired infections. However, to the best of our knowledge there are limited South African studies that have investigated the association between damage to the mucosal linings and the acquisition of HIV infections. We hypothesize that in this cohort of women, a higher rate of HIV seroconversions will be observed for women who present with evidence of mucosal damage.
  
  
  METHODS
  We undertook a secondary analysis of the Methods for Improving Reproductive Health in Africa (MIRA) trial that assessed the effectiveness of the latex diaphragm and lubricant gel on HIV prevention among women. Participants underwent a physical examination which included a pelvic examination to detect the presence of mucosal abnormalities. During the physical examinations, the study clinicians examined the genitalia, cervix and vagina for signs of epithelial disruptions and abnormal vaginal discharge. The association between the various genital factors and HIV seroconversion was modeled using Cox proportional hazards regression analysis.
  
  
  RESULTS
  In this cohort of 1485 women that had enrolled to participate in the study, women that had presented with genital epithelial disruptions and abnormal vaginal discharge were shown to be at highest risk for HIV acquisition (Hazard Ratio (HR): 4.30, 95% CI: 2.25, 8.22, p <0001, HR: 2.37, 95% CI: 1.69, 3.33, p <0.001) respectively. In addition, the Kaplan Meier analysis showed that the highest number of seroconversions was observed in women that had disrupted genital epithelia (27 per 100/py, 95% CI: 15.0, 50.7) and abnormal vaginal discharge (12 per 100/py, 95% CI: 9.70, 16.7). Other significant factors included: genital signs and symptoms (HR: 1.67, 95% CI: 1.07, 2.61, p = 0.02) and genital ulcers/sores (HR: 1.79, 95% CI: 1.05, 3.06, p = 0.03).
  
  
  CONCLUSIONS
  We have shown that damage to the mucosal epithelial lining increases a women's risk of HIV seroconversion. Future studies that provide an in depth understanding of the mechanisms associated with the FGT and mucosal immunity will be most valuable. An understanding of all of these mechanisms will be key in directing the advancement of products most suitable for combating HIV infection in women.
  
  
  BACKGROUND
  This study was registered with ClinicalTrials.gov,number NCT00121459 on the 28th February 2007.
authors.affiliation: HIV Prevention Research Unit, Medical Research Council, 123 Jan Hofmeyr Road, Westville, Durban, 3630, South Africa. Nathlee.abbai@mrc.ac.za.
authors.forename: Nathlee Samantha
authors.initials: NS
authors.lastname: Abbai
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Handan
authors.initials: H
authors.lastname: Wand
authors.affiliation: HIV Prevention Research Unit, Medical Research Council, 123 Jan Hofmeyr Road, Westville, Durban, 3630, South Africa.|Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Gita
authors.initials: G
authors.lastname: Ramjee
mesh_terms: D000293:Adolescent; D000328:Adult; D001685:Biological Factors; D004198:Disease Susceptibility / Q000150:complications / Q000473:pathology; D005260:Female; D005835:Genitalia / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control*; D015497:HIV-1 / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D012725:Sexual Behavior / Q000706:statistics & numerical data*; D013019:South Africa / Q000453:epidemiology
chemical_list: D001685:Biological Factors
keywords: Abnormal vaginal discharge; Epithelial disruption; HIV infection; Sexually transmitted infections