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Identification and Distribution of HIV Type 1 Genetic Diversity and Protease Inhibitor Resistance–Associated Mutations in Shanghai, P. R. China

Zhong, Ping; Kang, Laiyi; Pan, Qichao; Konings, Frank; Burda, Sherri; Ma, Liying; Xue, Yile; Zheng, Xiaohong; Jin, Zicheng; Nyambi, Phillipe

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2003 - Volume 34 - Issue 1 - p 91-101
Epidemiology & Social Science

Objective To investigate the genetic diversity of the HIV-1 circulating in Shanghai and to analyze the mutations in the protease (PR) gene associated with resistance to protease inhibitors (PIs).

Design The genetic diversity of HIV-1 and PI resistance–associated mutations was studied in 40 Shanghai HIV-1-seropositive treatmentnaive residents. The patients studied were exposed to the infection mainly through contaminated blood products (hemophiliacs) (n = 17) and sexual contacts (n = 19). Samples from 2 injecting drug users (IDUs) and 2 children born to HIV-1 infected mothers were also analyzed.

Methods HIV-1 partial gag, pol, and env genes in infected plasma samples were amplified by reverse transcriptase polymerase chain reaction, sequenced, and phylogenetically analyzed. Analysis of PI resistance–associated amino acid substitution in PR was performed.

Results HIV - 1 genes in 38 of the 40 plasma samples were successfully amplified and analyzed. Polymerase chain reaction amplification was successful for 16/17 hemophilia patients and 18/19 sexually infected individuals. While all the 16 hemophilia patients infected through contaminated blood products were infected with subtype B′, the 18 patients infected through sexual contact were infected with several subtypes including subtype A (n = 2), B (n = 4), B′ (n = 1), C (n = 2), CRF08_BC (n = 1), CRF01_AE (n = 7), and intersubtype recombinant CRF01_AE/B (n = 1). The 2 IDUs were infected with CRF08_BC and the 2 children born to HIV-1 infected mothers were infected with subtype B′ and CRF01_AE. PI resistance–associated amino acid substitutions were found at 1 codon in primary and 7 codons in secondary regions of the PR gene. Amino acid substitutions were more frequently found in the B/B′ sequences (69%) than in the non-B sequences (31%). Substitutions characteristic with the subtype B/B′ sequences mainly among hemophiliacs included L63P (87%), A71V/T (27%), and V77I (93%) while those that characterized the non-B sequences mainly found among heterosexuals included M36I (69%) and K20R (19%).

Conclusion This study reveals the presence of multiple HIV-1 subtypes and recombinants infecting Shanghai residents. The broad HIV-1 diversity is being introduced into this city through heterosexual contacts. This study also reveals that viruses infecting these treatment-naive patients have acquired both primary or secondary mutations in their PR genes. These studies should provide the basis for further epidemiologic surveys of HIV-1 subtypes and set strategies for treatment intervention and vaccine programs.

From the Department of Pathology, New York University School of Medicine, New York, New York (Drs Zhong, Burda, Ma, and Nyambi); Shanghai Municipal Center for Disease Control and Prevention (Drs Zhong, Kang, Pan, Xue, Zheng, and Jin) and Shanghai Municipal Center for AIDS Research, P.R.China (Drs Zhong, Kang, Pan, Xue, Zheng, and Jin); Department of Microbiology, New York University School of Medicine (Dr Konings), and Research Enhancement Award Program, VA Medical Center, New York, New York (Dr Nyambi).

Received for publication February 21, 2003; accepted May 13, 2003.

Research funds from the Department of Veterans Affairs and the New York City Council funds to the Institute for Urban and Global Health at NYU School of Medicine.

Reprints: Phillipe Nyambi, Department of Pathology, New York University School of Medicine, c/o V.A. Medical Center, 423 E. 23rd Street, Room 18124N, New York, NY 10010 (e-mail: phillipe.nyambi@med.nyu.edu).

Copyright © 2003 Wolters Kluwer Health, Inc. All rights reserved.