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Multi-center Nationwide Survey of Drug-resistant HIV-1 in Newly Diagnosed HIV/AIDS Patients in Japan from 2003 to 2004
H Gatanaga1, T Koike2, T Asagi3, H Tsukada4, M Kondo5, A Masakane6, T Kaneda7, H Mori8, R Minami9, Wataru Sugiura*10, and Japanese Drug Resistance HIV-1 Surveillance Network
1Intl Med Ctr, Toyama, Japan; 2Hokkaido Univ Sch of Med, Japan; 3Sendai Med Ctr, Japan; 4Niigata Univ Graduate Sch of Med and Dental Sci, Japan; 5Kanagawa Prefectural Inst of Publ Hlth, Japan; 6Ishikawa Prefectural Central Hosp, Japan; 7Nagoya Med Ctr, Japan; 8Osaka Prefectural Inst of Publ Hlth, Japan; 9Kyusyu Med Ctr, Japan; and 10NIAID, NIH, DHHS, Bethesda, MD, US
Background:
HAART has improved the HIV/AIDS prognosis
dramatically in the past decade. However, the use of ART has enabled the virus
to break out and develop resistance, and an increasing number of drug-resistant
cases has raised the risk of new infection by drug-resistant
strains. Indeed, reports from developed countries describe that 10 to 20% of
new HIV/AIDS patients are infected by drug-resistant viruses. In this study, we
attempt to clarify the prevalence of drug-resistant infection among newly
diagnosed HIV-1 cases in Japan.
Methods: This survey involved 8 HIV/AIDS clinical centers,
3 public health laboratories, and the National Institute of Infectious
Diseases. HIV/AIDS patients with both acute and chronic infections, newly diagnosed
between January 2003 and December 2004, were enrolled in the study. Drug
resistance genotyping was carried out by in-house protocol. In brief, viral RNA
extracted from 200 mL plasma was reverse transcribed, and 1.3
Kbps protease and RT regions were amplified by nested polymerase chain reaction
(PCR). Subsequently, cycle sequencing reactions were performed by BigDye Terminator, and the products were analyzed by
auto-sequencer. Drug-resistant mutations were determined by IAS-USA drug
resistance definition chart.
Results: Data from a total of 576 cases were collected and
analyzed. Patient demographics are as follows:
age ,37 years (29 to 43); 519 male and 57
female; 391 homosexual and 143 heterosexual. Thus, currently the major population
of newly diagnosed HIV/AIDS cases in Japan is homosexuals. Of 576 cases,
18 (3.1%) were found to possess drug-resistant mutation within the drug target
genome. As for nucleoside reverse transcriptase inhibitor (NRTI)-resistant
mutations, M184V (4 cases) and M41L (4) were observed. As for non-NRTI (NNRTI)-resistant
mutations K103N (2), V106A (1), and V108I (3) were detected. For protease
inhibitor (PI)-resistant mutations, five cases of M46I/L were the only detected
major PI mutations.
Conclusions:
The overall prevalence of drug-resistant cases for
2003 to 2004 was 3.1% in Japan.
This number is significantly lower than that reported by other developed countries.
However, the rapid increase in both newly diagnosed HIV/AIDS cases and patients
exposed to ART alerts us to the persistent risk of the spread of drug-resistant
HIV-1, and indicates the importance of continuous monitoring of newly diagnosed
HIV/AIDS cases.
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