title: Estimation of the Undiagnosed Intervals of HIV-Infected Individuals by a Modified Back-Calculation Method for Reconstructing the Epidemic Curves.
abstract: BACKGROUND
  Undiagnosed infections accounted for the hidden proportion of HIV cases that have escaped from public health surveillance. To assess the population risk of HIV transmission, we estimated the undiagnosed interval of each known infection for constructing the HIV incidence curves.
  
  
  METHODS
  We used modified back-calculation methods to estimate the seroconversion year for each diagnosed patient attending any one of the 3 HIV specialist clinics in Hong Kong. Three approaches were used, depending on the adequacy of CD4 data: (A) estimating one's pre-treatment CD4 depletion rate in multilevel model;(B) projecting one's seroconversion year by referencing seroconverters' CD4 depletion rate; or (C) projecting from the distribution of estimated undiagnosed intervals in (B). Factors associated with long undiagnosed interval (>2 years) were examined in univariate analyses. Epidemic curves constructed from estimated seroconversion data were evaluated by modes of transmission.
  
  
  RESULTS
  Between 1991 and 2010, a total of 3695 adult HIV patients were diagnosed. The undiagnosed intervals were derived from method (A) (28%), (B) (61%) and (C) (11%) respectively. The intervals ranged from 0 to 10 years, and were shortened from 2001. Heterosexual infection, female, Chinese and age >64 at diagnosis were associated with long undiagnosed interval. Overall, the peaks of the new incidence curves were reached 4-6 years ahead of reported diagnoses, while their contours varied by mode of transmission. Characteristically, the epidemic growth of heterosexual male and female declined after 1998 with slight rebound in 2004-2006, but that of MSM continued to rise after 1998.
  
  
  CONCLUSIONS
  By determining the time of seroconversion, HIV epidemic curves could be reconstructed from clinical data to better illustrate the trends of new infections. With the increasing coverage of antiretroviral therapy, the undiagnosed interval can add to the measures for assessing HIV transmission risk in the population.
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.|Institute for Global Health & Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.|University of North Carolina Project-China, Guangzhou, Guangdong, China.
authors.forename: Ngai Sze
authors.identifier: http://orcid.org/0000-0003-3788-8114
authors.initials: NS
authors.lastname: Wong
authors.affiliation: Special Preventive Programme, Department of Health, Hong Kong Special Administrative Region Government, Hong Kong, China.
authors.forename: Ka Hing
authors.initials: KH
authors.lastname: Wong
authors.affiliation: Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China.
authors.forename: Man Po
authors.initials: MP
authors.lastname: Lee
authors.affiliation: Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Owen T Y
authors.initials: OT
authors.lastname: Tsang
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Denise P C
authors.initials: DP
authors.lastname: Chan
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Shui Shan
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D058872:Epidemics / Q000706:statistics & numerical data*; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology / Q000635:transmission; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D015233:Models, Statistical; D062486:Public Health Surveillance / Q000379:methods*; D055815:Young Adult