title: Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients.
abstract: BACKGROUND
  Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.
  
  
  METHODS
  Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm(3) or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.
  
  
  RESULTS
  A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46-241) cells/mm(3). Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm(3) in 2008 to a peak of 302 cells/mm(3) after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27-0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18-1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24-2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77-5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19-3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31-3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18-7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.-4.36; p=0.035).
  
  
  CONCLUSIONS
  Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.
authors.affiliation: Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; sasisopin.kie@mahidol.ac.th.
authors.forename: Sasisopin
authors.initials: S
authors.lastname: Kiertiburanakul
authors.affiliation: The Kirby Institute, University of New South Wales, Kensington, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Boettiger
authors.affiliation: Queen Elizabeth Hospital, Hong Kong, China SAR.
authors.forename: Man Po
authors.initials: MP
authors.lastname: Lee
authors.affiliation: University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Sharifah Fs
authors.initials: SF
authors.lastname: Omar
authors.affiliation: National Center for Global Health and Medicine, Toyama Shinjuku-ku, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Tanuma
authors.affiliation: Tan Tock Seng Hospital, Singapore.
authors.forename: Oon Tek
authors.initials: OT
authors.lastname: Ng
authors.affiliation: TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Durier
authors.affiliation: HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.affiliation: Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: Rossana
authors.initials: R
authors.lastname: Ditangco
authors.affiliation: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Romanee
authors.initials: R
authors.lastname: Chaiwarith
authors.affiliation: Chiang Rai Prachanukroh Hospital, Chiang Rai, Thailand.
authors.forename: Pacharee
authors.initials: P
authors.lastname: Kantipong
authors.affiliation: Hospital Sungai Buloh, Sungai Buloh, Malaysia.
authors.forename: Christopher Kc
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia.
authors.forename: Mahiran
authors.initials: M
authors.lastname: Mustafa
authors.affiliation: National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia.
authors.forename: Vonthanak
authors.initials: V
authors.lastname: Saphonn
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Winai
authors.initials: W
authors.lastname: Ratanasuwan
authors.affiliation: Faculty of Medicine, Udayana University & Sanglah Hospital, Bali, Indonesia.
authors.forename: Tuti Parwati
authors.initials: TP
authors.lastname: Merati
authors.affiliation: YRG Centre for AIDS Research and Education, Chennai, India.
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.affiliation: Taipei Veterans General Hospital and AIDS Prevention and Research Centre, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wing Wai
authors.initials: WW
authors.lastname: Wong
authors.affiliation: Beijing Ditan Hospital, Beijing, China.
authors.forename: Fujie
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Bach Mai Hospital, Hanoi, Vietnam.
authors.forename: Thanh Thuy
authors.initials: TT
authors.lastname: Pham
authors.affiliation: Institute of Infectious Diseases, Pune, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Pujari
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Working Group on AIDS Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
authors.forename: Evy
authors.initials: E
authors.lastname: Yunihastuti
authors.affiliation: Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Somnuek
authors.initials: S
authors.lastname: Sungkanuparph
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001208:Asia / Q000453:epidemiology; D018791:CD4 Lymphocyte Count / Q000706:statistics & numerical data*; D057210:Delayed Diagnosis / Q000706:statistics & numerical data; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents
keywords: AIDS; Asia; CD4; HIV; antiretroviral therapy; trends