To examine the prevalence of illicit drug use among men who have sex with men (MSM) with HIV-1 infection in Japan, where the life-time prevalence of illicit drug use in the general population is only 2.9%.
A single-center cross-sectional study at a large HIV clinic in Tokyo, which treats approximately 15% of HIV-1 infected patients in Japan.
The prevalence of illicit drug use and the assciation of characteristics and social demographics of the patients with illicit drug use were examined. Patients who visited the clinic for the first time from 2005 to 2010 were enrolled. Relevant variables were collected using a structured interview and from the medical records. Multivariate logistic regression analyses were applied to estimate the odds of association of MSM over non-MSM HIV-infected patients with illicit drug use.
1,196 patients were enrolled. They were mostly Japanese men of relatively young age. Illicit drug use (including injection drugs) was reported by 35% of the patients (by 40% of MSM), and 4% were IDU while 5% were on methamphetamine. 2% of the population was arrested due to illicit drugs. MSM was significantly associated with illicit drug use (adjusted OR = 4.60; 95% CI, 2.88–7.36; p<0.01). Subgroup analysis of the patients stratified by three age groups (≤30, 31 to 40, and >40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤30 years: adjusted OR = 7.56; 95% CI, 2.86–20.0; p<0.01), followed by the oldest (>40 years: adjusted OR = 6.15; 95% CI, 2.40–15.8; p<0.01), and the weakest in the group aged 31 to 40 (adjusted OR = 3.39; 95% CI, 1.73–6.63; p<0.01).
Citation: Nishijima T, Gatanaga H, Komatsu H, Takano M, Ogane M, Ikeda K, et al. (2013) High Prevalence of Illicit Drug Use in Men Who Have Sex with Men with HIV-1 Infection in Japan. PLoS ONE 8(12): e81960. https://doi.org/10.1371/journal.pone.0081960
Editor: Wenzhe Ho, Temple University School of Medicine, United States of America
Received: May 8, 2013; Accepted: October 18, 2013; Published: December 10, 2013
Copyright: © 2013 Nishijma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by Grants-in Aid for AIDS research from the Japanese Ministry of Health, Labour, and Welfare (H23-AIDS-001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Illicit drug users, especially injection drug users (IDU), are at high risk of infection with HIV-1 , . They are one of the “difficult to reach” populations, especially with regard obtaining accurate prevalence data . In Japan, the prevalence of illicit drug use in the general population is only 2.9% according to the 2009 Nationwide General Population Survey on Drug Use and Abuse ,  (http://www.ncnp.go.jp/nimh/pdf/h21.pdf. in Japanese) (http://www.mhlw.go.jp/bunya/iyakuhin/yakubuturanyou/torikumi/dl/index-04.pdf. in Japanese). To our knowledge, however, no study has examined the prevalence of illicit drug use among patients with HIV-1 infection in Japan.
Among patients with HIV-1 infection, illicit drug use is associated with lower antiretroviral therapy (ART) uptake and inferior adherence –, which leads to suboptimal treatment outcome, compared with patients with other risk categories –. The aim of the present study was to examine the prevalence of illicit drug use in patients with HIV-1 infection and its association with characteristics of the patients in Japan, in order to establish effective intervention strategies.
This study was approved by the Human Research Ethics Committee of National Center for Global Health and Medicine, Tokyo, Japan. The Committee waived a written informed consent, because this study only used data of patients from routine clinical practice. However, at our clinic each patient provided a written informed consent for the clinical and laboratory data to be used and published for research purposes . We conducted this study according to the principles expressed in the Declaration of Helsinki.
This study was designed and reported according to the recommendations of Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement . We performed a single center cross-sectional study of patients with HIV-1 infection to examine the prevalence of illicit drug according to patient characteristics including sexual orientation, primarily focusing on men who have sex with men (MSM). Illicit drugs were defined as legally prohibited substances in Japan; They included amyl nitrite and 5-methoxy-diisopropyltryptamine, which became prohibited by law in 2006 and 2005, respectively, in Japan . This study was conducted at the AIDS Clinical Center, Tokyo. Our facility is one of the largest clinics for HIV care in Japan with more than 3,300 registered patients . Considering that the total reported number of patients with HIV-1 infection is 21,415 by the end of 2011, this clinic treats approximately 15% of the HIV-1 infected patients in Japan (http://api-net.jfap.or.jp/status/2011/11nenpo/hyo_02.pdf. in Japanese).
The study population comprised patients with HIV-1 infection, aged >17 years, who visited our clinic for the first time from January 1, 2005 to August 31, 2010. The following exclusion criteria were applied; 1) those who visited the clinic for a second opinion, 2) those referred to other facilities on their first or second visit. These patients were excluded because the structured interview on social demographics was often not conducted in these patients, 3) patients infected through contaminated blood products (e.g. hemophiliacs) and mother to child transmission, and 4) patients who refused to be included in the study.
Variables were collected through a structured interview conducted at the first visit as part of routine clinical practice by the nurses specializing at the HIV outpatient care. The interview by these “coordinator nurses” included the following variables: history of illicit drug use and injection drug use (and their types if available), perceived route of transmission, sexual orientation (men were asked whether they have sex with men), history of gay bathhouse use (if MSM), working status, and living status (alone or with someone else) . Because interviews could potentially underestimate the prevalence of illicit drug use, we also searched the medical records for information on illicit drug use and related variables covering the period from the first visit to December 2012. Data of age, sex, ethnicity, current treatment status for HIV infection, and history of AIDS (defined as history of or concurrent 23 AIDS-defining diseases set by the Japanese Ministry of Health, Labour and Welfare) were obtained from the medical records (http://www.haart-support.jp/pdf/guideline2012.pdf in Japanese). The laboratory data of CD4 cell count, HIV-1 viral load, hepatitis C antibody on the first visit were also collected, and when these tests were not conducted on that day, data within three months from the first visit were used.
Patients' characteristics and social demographics were compared between MSM and non-MSM groups by the Student's t-test for continuous variables and by either the χ2 test or Fisher's exact test for categorical variables. Logistic regression analysis was used to estimate the odds of association of MSM, relative to non-MSM, with illicit drug use. The odds of association of each basic demographics, baseline laboratory data, and other medical conditions listed above was also estimated with univariate analysis.
To estimate the odds of association of MSM over non-MSM with illicit drug use, we conducted multivariate logistic regression analysis adjusted by age and ethnicity. Age and ethnicity (Japanese) were selected among four variables with p value <0.05 in univariate analysis, because age is a basic demographic and the literature had reported that population/ethnicity can affect the prevalence of illicit drug use . The two variables; “ART” and “history of AIDS” were not included because they were not considered to be related to illicit drug use.
To estimate the odds of association of different age categories with illicit drug use, we divided the group into three age subgroups: ≤30, 31 to 40, and >40 years. Then, the abovementioned multivariate analysis was conducted for each subgroup.
Statistical significance was defined at two-sided p value of <0.05. We used odds ratios (ORs) and 95% confidence intervals (95% CIs) to estimate the odds of association of each variable with illicit drug use. All statistical analyses were performed with The Statistical Package for Social Sciences ver. 20.0 (SPSS, Chicago, IL).
During the study period, 1,366 patients with HIV-1 infection visited the AIDS Clinical Center for the first time, and 170 patients were excluded from the analysis based on the abovementioned exclusion criteria (Figure 1). For the 1,196 patients included in the study, the perceived route of transmission was male-to-male sexual contact in 948 (79%), heterosexual contact in 173 (14%), IDU in 22 (2%), and unknown in 53 (4%). The majority of the study patients were relatively young Japanese men with a median age of 36 years. Most patients were ART-naïve, with a median CD4 count of 245/µl (Table 1).
Among the 1,196 patients, 415 (35%) had used or were illicit drug users, and 53 (4%) were IDUs while 63 (5%) reported using methamphetamine. With regard to social history, 27 (2%) had been detained or arrested due to possession or use of illicit drugs (Table 1). Among the illicit drugs used, amyl nitrite and 5-methoxy-diisopropyltryptamine were the most commonly named by the patients. 3,4-methylenedioxymethamphetamine, cannabis, heroin, cocaine, and opium were also mentioned (numbers not counted except for methamphetamine).
Of the 1,196 patients, 973 (81%) were MSM regardless of the perceived route of transmission (e.g., if a patient considered to have been infected with HIV-1 through injection drug use and was MSM, he was classified as MSM in Table 1). Compared with non-MSM patients, MSM were significantly younger and more likely to be Japanese. MSM patients were more likely to have experienced illicit drugs [392 (40%)] than non-MSM [23 (10%), p<0.01], and have used methamphetamine [57 (6%) versus 6 (3%), p = 0.07], and to have been arrested/detained due to illicit drug use/possession [(26 (3%) versus 1 (0.4%), p = 0.04) (Table 1). There was no difference in the percentage of IDUs among the MSM and non-MSM groups [44 (5%) versus 9 (4%), p = 0.73]. The CD4 count of MSM patients tended to be higher, and MSM were less likely to present with AIDS than non-MSM, although HIV viral load of MSM was significantly higher than that of non-MSM. MSM were more likely to have a job and be living alone. Further analysis showed that 47% of MSM patients used a gay bathhouse, and among them, the prevalence of illicit drug use was higher (49%) than all MSM (40%). The prevalence of illicit drug use was even higher in MSM aged ≤30 years (52%).
Univariate analysis showed a significant relationship between MSM and illicit drug use (OR = 5.87; 95% CI, 3.74–9.20; p<0.01) (Table 2, Model 1). Furthermore, younger age, being Japanese, on ART, and history of AIDS were associated with illicit drug use. On the other hand, without a job, living alone, and positive HCV antibody were not associated with illicit drug use. Multivariate analysis identified MSM to be significantly associated with illicit drug use after adjustment for age and Japanese (adjusted OR = 4.60; 95% CI, 2.88–7.36; p<0.01) (Table 2, Model 2).
Subgroup analysis of the patients stratified by three age groups (≤30, 31 to 40, and >40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤30 years: adjusted OR = 7.56; 95% CI, 2.86–20.0; p<0.01), followed by the oldest (>40 years: adjusted OR = 6.15; 95% CI, 2.40–15.8; p<0.01), and the weakest in the group aged 31 to 40 (adjusted OR = 3.39; 95% CI, 1.73–6.63; p<0.01) (Table 3).
The prevalence of illicit drug use among patients with HIV-1 infection in this large urban HIV clinic in Tokyo, which treats approximately 15% of patients with HIV-1 infection in Japan, was high at 35%. The prevalence was higher among HIV-1 infected MSM (40%), especially among young MSM aged ≤30 years (52%). Furthermore, HIV-1 infected MSM were more likely to use methamphetamine and to be arrested due to illicit drugs, compared with non-MSM. It should be emphasized that these numbers are likely to be underreported, since some patients would not admit illicit drug use to the interviewers on their first visit.
To our knowledge, this is the first study on the prevalence of illicit drug use among patients with HIV-1 infection in Japan. Although the prevalence of illicit drug use is considered extremely low among the general population in Japan with lifetime prevalence of 2.9% in 2009, high prevalence of illicit drug use in patients with HIV-1 infection, especially among HIV-1 infected MSM, was demonstrated ,  (http://www.ncnp.go.jp/nimh/pdf/h21.pdf. in Japanese) (http://www.mhlw.go.jp/bunya/iyakuhin/yakubuturanyou/torikumi/dl/index-04.pdf. in Japanese). The prevalence of methamphetamine use and incarceration due to illicit drug was also high, suggesting a substantial impact of illicit drugs, not only on the well-being of this population in terms of both medical and social perspectives, but also on public health perspectives , .
In Japan, the number of illicit drug users arrested in 2010 was 14,965. Among these, 12,200 used methamphetamine, followed by cannabis (2,367), while only several hundred at most used other drugs (http://www.mhlw.go.jp/bunya/iyakuhin/yakubuturanyou/torikumi/dl/index-01.pdf in Japanese). Of note, the number of arrestees due to other injectable drugs, such as heroin and cocaine, was small (22 and 112, respectively). Thus, most injection drug users in Japan are methamphetamine users. Majority of the patients identified as IDU in this study were considered to be methamphetamine users as well.
By the end of 2011, of 19,976 patients (excluding those infected with contaminated blood products) reported to be infected with HIV-1, 108 (0.5%) were reported to be infected through injection drug use according to the surveillance conducted by the AIDS Surveillance Committee of the Japanese Ministry of Health, Labour and Welfare (http://api-net.jfap.or.jp/status/2011/11nenpo/hyo_02.pdf in Japanese). The prevalence of IDUs in this study is substantially higher; 53 (4%) of the 1,196 were IDUs, suggesting a considerable underreporting of IDU in the surveillance data. It is well known that for IDUs, prognosis is much worse than non-injecting drug users, as one multicenter study conducted in Europe and North America reported that IDUs experienced approximately five times higher mortality rates than patients infected through sexual intercourse . Although the prevalence of IDUs among patients with HIV-1 infection in Japan is still much lower than that in neighboring countries, such as Taiwan (27.6%) and China (24.3%), there is an urgent need to develop effective prevention programs for HIV-1 infected illicit drug users  (http://www.unaids.org.cn/download/2009%20China%20Estimation%20Report-En.pdf) (http://www.cdc.gov.tw/english/list.aspx?treeid=00ED75D6C887BB27&nowtreeid=334C2073091C8677).
Although the prognosis of injection drug users is reported to be worse than that of non-injection drug users , this study primarily focused on illicit drug use as a whole, rather than injection drug use. This is because only a few studies focused on illicit drug use among HIV-1 infected patients, although a large number of studies focused on injection drugs –. Illicit drug use in patients with HIV-1 infection is an important issue, because not only illicit drug use lead to inferior treatment outcome compared with non users –, but also non injection drug users are prone to practice high risk sexual behaviors, which might lead to transmission of HIV and other infectious diseases , . Studies from the US reported that especially MSM who use illicit drugs are at high risk for HIV and sexual transmitted infections due to close associations between risky sexual behaviors and illicit drug use ,  Furthermore, illicit drug use, especially opioid use, can be a trajectory into injection drug use , .
Several limitations need to be acknowledged. First, due to the nature of single-center study, this is a convenience sample and the results of this study do not necessarily represent the prevalence of illicit drug use in all patients with HIV-1 infection in Japan. However, as mentioned above, our clinic treats approximately 15% of the total HIV patients in Japan, and furthermore, most HIV-1 infected patients reside in urban areas such as Tokyo metropolitan area (http://api-net.jfap.or.jp/status/2011/11nenpo/hyo_02.pdf in Japanese). Thus, the discrepancy in the prevalence of illicit drug use between the study patients and all HIV patients in Japan should not be too large. Second, the structured interview method to collect data cannot avoid underreporting of illicit drug usage. Thus, the prevalence of illicit drug use in this population is very likely to be higher than what is reported here. However, underreporting to a certain degree is unavoidable with regard to issues such as illicit drug use .
In conclusion, the prevalence of illicit drug use in patients with HIV-1 infection in this large HIV clinic in Tokyo was high at 35%, and was higher in HIV-1 infected MSM (40%). Despite the low prevalence of IDUs (0.5%) among HIV-infected patients reported by the AIDS Surveillance Committee, 5% of patients in this study were IDUs. All relevant parties to the issue of illicit drug use in patients with HIV-1 infection need to recognize that illicit drug use is a huge burden in care and well-being of this population even in Japan, a country with very low prevalence of illicit drug use in the general population. Appropriate measures for prevention and intervention of illicit drug use are urgently needed to ensure proper treatment and prevention of spread of HIV infection.
The authors thank Dr. Kiyoshi Wada, Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, and Dr. Keishiro Yajima, AIDS Medical Center, National Hospital Organization Osaka National Hospital, for valuable comments for the manuscript. The authors also thank “coordinator nurses” who conducted the structured interviews (Ruiko Yakuwa, Beni Ito, Yuko Sugino, Miki Koyama, Kenji Takeda, Megumi Shimada, Jongmi Seo, Yuki Yamada, Kyoko Ishigaki), and all other clinical staff at the AIDS Clinical Center, for their help in the completion of this study.
Conceived and designed the experiments: TN HG HK MT SO. Performed the experiments: MO KI. Analyzed the data: TN HK HG MT SO. Contributed reagents/materials/analysis tools: MO KI SO. Wrote the paper: TN HG MT SO.
- 1. Lehman JS, Allen DM, Green TA, Onorato IM (1994) HIV infection among non-injecting drug users entering drug treatment, United States, 1989–1992. Field Services Branch. AIDS 8: 1465–1469.
- 2. Hahn RA, Onorato IM, Jones TS, Dougherty J (1989) Prevalence of HIV infection among intravenous drug users in the United States. JAMA 261: 2677–2684.
- 3. Magnani R, Sabin K, Saidel T, Heckathorn D (2005) Review of sampling hard-to-reach and hidden populations for HIV surveillance. AIDS 19 Suppl 2S67–72.
- 4. Wada K (2011) The history and current state of drug abuse in Japan. Ann N Y Acad Sci 1216: 62–72.
- 5. Tominaga M, Kawakami N, Ono Y, Nakane Y, Nakamura Y, et al. (2009) Prevalence and correlates of illicit and non-medical use of psychotropic drugs in Japan: findings from the World Mental Health Japan Survey 2002–2004. Soc Psychiatry Psychiatr Epidemiol 44: 777–783.
- 6. Wood E, Montaner JS, Tyndall MW, Schechter MT, O'Shaughnessy MV, et al. (2003) Prevalence and correlates of untreated human immunodeficiency virus type 1 infection among persons who have died in the era of modern antiretroviral therapy. J Infect Dis 188: 1164–1170.
- 7. Strathdee SA, Palepu A, Cornelisse PG, Yip B, O'Shaughnessy MV, et al. (1998) Barriers to use of free antiretroviral therapy in injection drug users. JAMA 280: 547–549.
- 8. Malta M, Magnanini MM, Strathdee SA, Bastos FI (2010) Adherence to antiretroviral therapy among HIV-infected drug users: a meta-analysis. AIDS Behav 14: 731–747.
- 9. Horstmann E, Brown J, Islam F, Buck J, Agins BD (2010) Retaining HIV-infected patients in care: Where are we? Where do we go from here? Clin Infect Dis 50: 752–761.
- 10. Weber R, Huber M, Rickenbach M, Furrer H, Elzi L, et al. (2009) Uptake of and virological response to antiretroviral therapy among HIV-infected former and current injecting drug users and persons in an opiate substitution treatment programme: the Swiss HIV Cohort Study. HIV Med 10: 407–416.
- 11. Milloy MJ, Marshall BD, Kerr T, Buxton J, Rhodes T, et al. (2012) Social and structural factors associated with HIV disease progression among illicit drug users: a systematic review. AIDS 26: 1049–1063.
- 12. Porter K, Babiker A, Bhaskaran K, Darbyshire J, Pezzotti P, et al. (2003) Determinants of survival following HIV-1 seroconversion after the introduction of HAART. Lancet 362: 1267–1274.
- 13. Nishijima T, Gatanaga H, Komatsu H, Tsukada K, Shimbo T, et al. (2012) Renal function declines more in tenofovir- than abacavir-based antiretroviral therapy in low-body weight treatment-naive patients with HIV infection. PLoS One 7: e29977.
- 14. Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, et al. (2007) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Epidemiology 18: 805–835.
- 15. Hidaka Y, Ichikawa S, Koyano J, Urao M, Yasuo T, et al. (2006) Substance use and sexual behaviours of Japanese men who have sex with men: a nationwide internet survey conducted in Japan. BMC Public Health 6: 239.
- 16. Nishijima T, Gatanaga H, Komatsu H, Takano M, Ogane M, et al. (2013) Illicit Drug Use Is a Significant Risk Factor for Loss to Follow Up in Patients with HIV-1 Infection at a Large Urban HIV Clinic in Tokyo. PLoS One 8: e72310.
- 17. Millett GA, Peterson JL, Wolitski RJ, Stall R (2006) Greater risk for HIV infection of black men who have sex with men: a critical literature review. Am J Public Health 96: 1007–1019.
- 18. Zwahlen M, Harris R, May M, Hogg R, Costagliola D, et al. (2009) Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries. Int J Epidemiol 38: 1624–1633.
- 19. Chen YM, Kuo SH (2007) HIV-1 in Taiwan. Lancet 369: 623–625.
- 20. Qian HZ, Stinnette SE, Rebeiro PF, Kipp AM, Shepherd BE, et al. (2011) The relationship between injection and noninjection drug use and HIV disease progression. J Subst Abuse Treat 41: 14–20.
- 21. Giordano TP, Hartman C, Gifford AL, Backus LI, Morgan RO (2009) Predictors of retention in HIV care among a national cohort of US veterans. HIV Clin Trials 10: 299–305.
- 22. Rice BD, Delpech VC, Chadborn TR, Elford J (2011) Loss to follow-up among adults attending human immunodeficiency virus services in England, Wales, and Northern Ireland. Sex Transm Dis 38: 685–690.
- 23. Ndiaye B, Ould-Kaci K, Salleron J, Bataille P, Bonnevie F, et al. (2009) Incidence rate and risk factors for loss to follow-up in HIV-infected patients from five French clinical centres in Northern France - January 1997 to December 2006. Antivir Ther 14: 567–575.
- 24. Mocroft A, Kirk O, Aldins P, Chies A, Blaxhult A, et al. (2008) Loss to follow-up in an international, multicentre observational study. HIV Med 9: 261–269.
- 25. Lebouche B, Yazdanpanah Y, Gerard Y, Sissoko D, Ajana F, et al. (2006) Incidence rate and risk factors for loss to follow-up in a French clinical cohort of HIV-infected patients from January 1985 to January 1998. HIV Med 7: 140–145.
- 26. Latkin CA, Knowlton AR, Sherman S (2001) Routes of drug administration, differential affiliation, and lifestyle stability among cocaine and opiate users: implications to HIV prevention. J Subst Abuse 13: 89–102.
- 27. Forrest DW, Metsch LR, LaLota M, Cardenas G, Beck DW, et al. (2010) Crystal methamphetamine use and sexual risk behaviors among HIV-positive and HIV-negative men who have sex with men in South Florida. J Urban Health 87: 480–485.
- 28. Mansergh G, Shouse RL, Marks G, Guzman R, Rader M, et al. (2006) Methamphetamine and sildenafil (Viagra) use are linked to unprotected receptive and insertive anal sex, respectively, in a sample of men who have sex with men. Sex Transm Infect 82: 131–134.
- 29. Lankenau SE, Teti M, Silva K, Jackson Bloom J, Harocopos A, et al. (2012) Initiation into prescription opioid misuse amongst young injection drug users. Int J Drug Policy 23: 37–44.
- 30. Pollini RA, Banta-Green CJ, Cuevas-Mota J, Metzner M, Teshale E, et al. (2011) Problematic use of prescription-type opioids prior to heroin use among young heroin injectors. Subst Abuse Rehabil 2: 173–180.