CRF01_AE subtype is associated with X4 tropism and fast HIV progression in Chinese patients infected through sexual transmission.
BACKGROUND
The molecular epidemiology of the HIV-1 CRF01_AE subtype as a risk factor for fast HIV-1 progression remains poorly understood.


METHODS
We analyzed HIV-1 tropism by utilizing samples from 201 treatment-naive patients in our multicenter cohort (12 research centers in different provinces of China). Tropism was determined by V3 loop sequencing. Data from 235 treatment-naive patients infected sexually (including aforementioned 201 patients) in this cohort with date of estimated seroconversion (EDS) were retrospectively evaluated. Median time from EDS to AIDS was analyzed by Kaplan-Meier curves. Hazard ratios were determined by Cox proportional model.


RESULTS
CRF01_AE subtype was predominant (46.0%), especially in the MSM group. Further analysis revealed that the proportion of X4 tropism was higher in the CRF01_AE subtype (45.5%) than in others (C/CRF07_BC/CRF08_BC, 4.3%; B, 6.1%; P <0.001). CRF01_AE subtype was associated with faster progression from EDS to AIDS (4.8 vs. 6.4 years, P = 0.018) compared with non-CRF01_AE subtypes. In a multivariate model, the adjusted hazard ratio (aHR) of CRF01_AE was 1.42 (95% confidence interval, CI 0.99-2.03, P = 0.057), independent of HIV-1 viral load; it was also associated with fast progression to advanced immunodeficiency (aHR, 1.81, 95% CI 1.03-3.18, P = 0.038).


CONCLUSIONS
CRF01_AE, a predominant HIV-1 subtype in Chinese HIV-1 sexually infected patients, tends to be associated with fast progression to AIDS and advanced immunodeficiency, which might be ascribed to high proportion of X4 tropism. Further investigation of these risk factors may have significant implications to clinical practice and policy-making.
aDepartment of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China bResearch Center for Asian Infectious Diseases, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan cJapan-China Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences dBeijing Youan Hospital, Capital Medical University, Beijing, China eDivision of Hematology and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada. *Yijia Li and Yang Han contributed equally to the writing of the study.
Yijia
Y
Li
Yang
Y
Han
Jing
J
Xie
Lijun
L
Gu
Wenjuan
W
Li
Huanling
H
Wang
Wei
W
Lv
Xiaojing
X
Song
Yanling
Y
Li
Jean-Pierre
JP
Routy
Takaomi
T
Ishida
Aikichi
A
Iwamoto
Taisheng
T
Li
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D002681:China; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000473:pathology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA; D013995:Time; D056189:Viral Tropism; D055815:Young Adult