Elsevier

Antiviral Research

Volume 88, Issue 1, October 2010, Pages 72-79
Antiviral Research

Trends in transmitted drug-resistant HIV-1 and demographic characteristics of newly diagnosed patients: Nationwide surveillance from 2003 to 2008 in Japan

https://doi.org/10.1016/j.antiviral.2010.07.008Get rights and content

Abstract

The emergence and transmission of drug-resistant human immunodeficiency virus-1 (HIV-1) compromises antiretroviral treatment for HIV-1. Thus, testing for drug resistance is recommended at diagnosis and before initiating highly active antiretroviral treatment. We conducted an epidemiological study enrolling newly diagnosed patients between 2003 and 2008 in our nationwide surveillance network. In the 6-year study period, the prevalence of drug-resistant HIV-1 among 2573 patients, consisting mainly of Japanese men in their late-30s and infected through male-to-male sexual contacts, followed an increasing trend from 5.9% (16/273) in 2003 to 8.3% (50/605) in 2008. Nucleoside reverse transcriptase inhibitor-associated mutations predominated in each year, with T215 revertants being the most abundant. The predictive factor for drug-resistant HIV-1 transmission was subtype B (OR = 2.36; p = 0.004), and those for recent HIV-1 infection were male gender (OR = 3.79; p = 0.009), MSM behavior (OR = 1.67; p = 0.01), Japanese nationality (OR = 2.31; p = 0.008), and subtype B (OR = 5.64; p < 0.05). Continued activities are needed to raise awareness of the risks of HIV-1 infection and complications of drug-resistant strains. Continued surveillance is also needed to understand trends in the HIV-1 epidemic.

Introduction

The emergence of drug-resistant human immunodeficiency virus type 1 (HIV-1) among patients under highly active antiretroviral therapy (HAART) limits the successful suppression of HIV-1 replication. Several years after the introduction of HAART, drug-resistant strains are being detected among newly diagnosed HAART-naïve patients, suggesting the transmission of drug-resistant HIV-1 from the treatment-exposed population. Thus, treatment-naïve patients have been recommended by the US Department of Health and Human Services, International AIDS Society-USA, and other drug-resistance testing guidelines to undergo drug resistance testing at diagnosis and before initiation of HAART (DHHS, 2009, Hirsch et al., 2000, Hirsch et al., 2008). Indeed, choosing effective antiretrovirals according to the results obtained from this testing has led to successful control of HIV-1 infection. Furthermore, the drug resistance testing at diagnosis helps to understand transmission of drug-resistant HIV-1 in HAART-naïve individuals which in turn may help prevent transmission events.

The prevalence of drug-resistant HIV-1 among treatment-naïve patients has been closely monitored and reported from many countries. Before and early in the HAART era, when only mono or dual therapy was available, the prevalence was as high as 10–20% (Boden et al., 1999, Gómez-Cano et al., 1998, Tambussi et al., 1998). However, after the introduction of antiretrovirals with better pharmacokinetics, such as ritonavir-boosted protease inhibitor (PI), the emergence of drug-resistant viruses seemed to decrease (Gallego et al., 2001, Maia Teixeira et al., 2006).

Furthermore, despite the great number of HIV-1-infected patients, the prevalence tended to be low in developing countries where patients had limited or no access to antiretroviral drugs, e.g., 0–4.2% in Africa (Bártolo et al., 2009, Mintsa-Ndong et al., 2009, Ndembi et al., 2008, Pillay et al., 2008), 1.5% in Cambodia (Nouhin et al., 2009), and 2.6% in Vietnam (Ishizaki et al., 2009). In contrast, in countries where antiretroviral drugs are more accessible, the prevalence has been higher, e.g., 5.2% in Thailand (Apisarnthanarak et al., 2008), 9.4% in Taiwan (Chang et al., 2008), 10.0% in India (Lall et al., 2008), 7.8% in Portugal (Palma et al., 2007), 9.0% in Germany (Sagir et al., 2007), 9.5% in Belgium (Vercauteren et al., 2008), 10.9% in France (Chaix et al., 2009), and 15.9% in the US (Eshleman et al., 2007).

In Japan, since the first HIV-1-infected case was identified in 1985, the annual number of reported cases has been increasing every year, reaching 15 451 by the end of 2008. With more people getting infected, larger numbers of patients are starting anti-HIV-1 treatment and the risk of emerging drug-resistant HIV-1 is increasing. To understand the trends in drug-resistant HIV-1 in Japan, a nationwide surveillance project has been in effect since 2003. In our previous report of surveillance results from 2003 to 2004, the prevalence of drug-resistant HIV-1 in newly diagnosed patients was 4.0% (Gatanaga et al., 2007). We have continued collecting and analyzing data from newly diagnosed HIV-1-infected patients at participating clinical and research facilities in Japan. We report here the prevalence of drug-resistant HIV-1 among newly diagnosed therapy-naïve patients between 2003 and 2008.

Section snippets

Sample

The study population included all the HIV-1-infected patients newly diagnosed between January 2003 and December 2008 at any of the participating HIV/AIDS clinics. Drug resistance genotypic tests were performed at 12 laboratories including 8 clinical laboratories at HIV/AIDS clinics, 3 public health laboratories, and the National Institute of Infectious Diseases. After patients agreed to participate in our surveillance project and gave informed consent, peripheral blood was drawn with EDTA

Majority of treatment-naïve patients are Japanese men who have sex with men (MSM) in mid-30s

The demographics of the 2573 newly diagnosed HIV-1-infected patients enrolled between 2003 and 2008 are summarized in Table 1. Male (n = 2397, 93.2%), Japanese (90.1%), and those infected through male-to-male sexual contact (68.9%) predominated, and the median age was 35. For the female cases (n = 170), high-risk heterosexual contact was the major risk factor (n = 152, 89.4%), and approximately half were non-Japanese (n = 63, 41.4%). Further analysis showed a significant association between the

Discussion

Our study results show that the proportion of drug-resistant HIV-1 among newly diagnosed cases in Japan increased slightly (by 2.4%) from 2003 to 2008, with fluctuations from year to year. Drug-resistant HIV-1 in HAART-naïve patients are transmitted from HAART-experienced patients with inadequate adherence or from other treatment-naïve individuals with drug-resistant strains, but not yet diagnosed or tested for drug-resistant HIV-1 (de Mendoza et al., 2005). Hence, drug-resistant mutations

Acknowledgments

We are grateful to all the patients who participated in our surveillance study. We thank the members of Japanese Drug Resistance HIV-1 Surveillance Network for their support and helpful discussions: Atsushi Ajisawa, Hitoshi Chiba, Takeshi Fujii, Yuko Fujikawa, Akira Fujita, Katsuyuki Fukutake, Tetsushi Goto, Shuji Hatakeyama, Igen Hongo, Masahide Horiba, Mitsunobu Imai, Tsuguhiro Kaneda, Akiro Kimura, Mitsuru Konishi, Shuzo Matsushita, Motoo Matsuura, Naoko Miyazaki, Itsuhiro Nakagiri, Masaaki

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