DOI: https://doi.org/10.21203/rs.2.22230/v1
Background The surge of methamphetamine use has been a complicating factor compounding the U.S. poly-drug use landscape. Infections of blood-borne virus including hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, arising from methamphetamine use continue to grow. This study aimed to examine the risk factors associated with blood-borne infections from HBV, HCV and HIV among people who used methamphetamine.
Methods Methamphetamine users were identified from five National Health and Nutrition Examination Survey (NHANES) cohorts from 2007 to 2016. We examined the association of sexual activities (sexual partners, sexual identity), drug use behaviors (poly-drug use, injection drug use, number of times drug use, age started using methamphetamine), demographics and socio-economic status with blood-borne infections using bivariate and multivariable logistic regressions.
Results There were 1,075 participants representing approximately 11,319,270 methamphetamine users in the U.S. with prevalence of blood-borne infections 13.4 per 100,000. Multivariable logistic regression analyses showed significant associations of blood-borne infections with age 50-59 years (adjusted odds ratio 6.32, 95% CI 1.35-29.69), living within poverty index 1-1.9 (2.80; 1.33 – 5.88), living below the poverty threshold (2.46; 1.14 – 5.28), having lower than high school education (3.57; 1.74 – 7.33), identified as men who have sex with men (MSM) (54.24; 13.80 – 213.24), using methamphetamine with other substances (5.86; 1.50 – 22.87), injection drug use (3.77; 1.93 – 7.36), and started using methamphetamine at age above 25 (2.18; 1.05 – 4.54).
Conclusions Polysubstance use, injection drug use, and MSM were strongly associated with increased risk of blood-borne infections among methamphetamine users.
Methamphetamine-related overdose has been increasing across the United States (U.S.) for the past several years. According to the Centers for Disease Control and Prevention (CDC) data, the overdose death rates of psychostimulants with abuse potential, primarily methamphetamine, had tripled between 2016 and 2017 [1]. Provisional data from CDC indicates that deaths involving psychostimulants continued to increase in 2018, despite a drop in overall overdose deaths observed at the same time [2]. In addition to increasing methamphetamine-related mortality, nonfatal harms arising from methamphetamine use continue to grow, including mental health disorders [3], violent and aggressive behavior [4], risky sexual behavior [4], sexually transmitted infection [5], harm to the fetus, and infection of blood-borne viruses [6, 7]. The pathogens of primary concern for blood-borne infectious diseases are the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) [8].
Methamphetamine use has been strongly associated with many outbreaks of blood-borne infections. Of the HBV patients identified in the 2003 HBV outbreak in Natrona County, Wyoming, eighty-eight percent reported injecting methamphetamine [9]. Methamphetamine use is prevalent among people living with HIV and AIDS, particularly among men who have sex with men [10]. Among the outbreak-related HIV infections identified during the 2014 HIV outbreak in Scott County, Indiana, 22% of the patients reported injecting methamphetamine [11]. A study characterizing methamphetamine use and HIV serostatus found 54% of the meth users were HIV positive [12]. Another study examined risk factors associated with HBV infections among people who used methamphetamine [13]. A prospective cohort study conducted in Canada determined that injecting methamphetamine independently predicted Hepatitis C infection among young, street-involved persons with injection drug use (IDU) [14].
Other than injection, methamphetamine non-injection drug use through smoking, swallowing or snorting also increases risk of blood-borne infections by negatively affecting judgment and triggering risky behaviors (e.g., unprotected sex) [15]. In addition to that, it is suggested that long-time methamphetamine use is associated with bleeding gums [16] and increasing risk of blood-borne infections through oral sex among sexual active population.
Fatal and nonfatal harms caused by rapidly increasing methamphetamine use are further compounded by existing opioid crisis, described by some scholars as “twin epidemics” [17]. Polysubstance use, such as co-occurring use of prescription opioids, illicit opioids, heroin, cocaine, or methamphetamine is now commonplace [18, 19]. Specifically, in 2017, opioids were involved in over half of the 10,333 psychostimulant-related deaths [20]. Deaths involving opioids and methamphetamine increased significantly by 14% between July 2017 and June 2018 [21]. People prefer to use multiple substances for various reasons: (a) to experience the synergistic effect; (b) to enhance the benefits of each substance; (c) to overcome dysphoria and manage withdrawal symptoms; (d) to experiment; (e) to avail cheaper substances; (f) to balance the stimulation from methamphetamine with sedation from opioid/heroin [22, 23]. However, since heroin, fentanyl and methamphetamine are all short-acting substances, persons with IDU tend to inject more frequently to stay “high”. The combined injection of methamphetamine and opioids, or sequential use of methamphetamine after opioids is associated with increased number of injections and increased probability of the reuse of syringes, thus, leading to elevated risk of blood-borne viruses [24–26].
Under this landscape of increasing polysubstance use, it is not clear how methamphetamine use affects the overall likelihood of blood-borne infections. A dynamic model investigating the excess risk of HIV and HCV infections among injection stimulant users suggests that a median of 5–10% of new HIV and 3–7% of new HCV infections in the following year could each be attributed to 10% increase in the prevalence of stimulant injection [6]. Another recent study found that women, poverty, IDU, and HCV infection were associated with increased risk of HBV infection among methamphetamine users [13]. CDC and a few state health departments have developed vulnerability assessment tools to identify counties at high risk of HIV and HCV; however, these tools do not include HBV [24, 27]. To date, no studies have used national data to examine factors associated with overall likelihood of blood-borne infections among methamphetamine users.
This study aims to examine risk factors associated with infection of blood-borne viruses among methamphetamine users in the National Health and Nutrition Examination Survey (NHANES). Findings from this study will identify vulnerable sub-population groups that are susceptible to infections from these blood-borne viruses.
Study data
The study population was identified from five NHANES cohorts from 2007 to 2016. Conducted by the National Center for Health Statistics (NCHS), NHANES is a continuous cross-sectional survey conducted every two years and is effective in determining the prevalence of major diseases and associated risk factors among adults and children in the U.S. [28, 29] The NHANES data are rich and unique in two ways. Firstly, it combines information collected from both interviews and physical examinations that are necessary to answer the research questions. The interviews include demographics, socio-economic status, drug use information, and health-related questions; and the physical examinations include medical measurements and results of laboratory tests. Secondly, each survey cycle examines a nationally representative sample, and findings from the study are generalizable to the U.S. Further details are described elsewhere [28].
Study population and sampling procedure
The study population comprised people who reported methamphetamine use. The flow chart in Figure 1 illustrates the process of case selection. The study included anyone who completed testing for any of the three sets of tests including HBV, HCV and HIV, and also answered “yes” to both questions “ever used cocaine/heroin/methamphetamine” and “ever used methamphetamine”. The study excluded anyone whose age was not between 18 and 69 years (as they were not eligible to answer drug use question) and anyone who obtained HBV immunity and was not infected by HBV thereafter.
Study design
The primary outcome measure was infections from any three blood-borne viruses. Presence of infection was defined as a positive result based on presence of total hepatitis B core antibody, or hepatitis C RNA, or HIV. Absence of infection was defined as being negative for all HBV lab markers including anti-HBc, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and negative for hepatitis C RNA and HIV lab markers. Indeterminate lab markers were coded as negative. People can only gain vaccine-induced immunity against HBV, therefore, participants who were solely HBsAb positive were also excluded from analyses.
According to previous literature, demographic characteristics (age, gender, race/ethnicity), socio-economic status (poverty index, health insurance, healthcare access, education), sexual activity (number of sexual partners in the past year, sexual identity), and drug use behaviors (number of drug use, IDU, number of times used methamphetamine, age started using methamphetamine) were known factors associated with infection of blood-borne virus. Specifically, the responses to questions including education, drug use, and sexual activity were limited to participants aged 20 to 59 years.
Statistical analysis
Descriptive analyses include both raw and weighted frequency and percent of all covariates mentioned above. Weighted frequencies and percentage for the combined ten years of data were calculated by multiplying the sample weight WTMEC2YR by 0.2. The Rao Scott Chi-squared statistic was calculated to assess the association between each covariate and outcome measure. Bivariate logistic regression and subsequent three-step sequential multivariable logistic regression models were developed to examine the risk factors associated with infections of blood-borne viruses among people who used methamphetamine. The outcome was either exposed to blood-borne virus (presence of infection) or susceptible to blood-borne virus (absence of infection). The main risk factors of interest were drug use behaviors (number of drug use, IDU, number of times used methamphetamine, and age started using methamphetamine). Step I model only included demographics; step II model further included socio-economic status and sexual activities; step III, the final model, included drug use behaviors in addition to all previous covariates. Unadjusted odds ratios (uORs) and their 95% confidence intervals (CIs) were reported from bivariate logistic regression models, and adjusted odds ratios (aORs) and their 95% CIs were reported from the three multivariable logistic regression models. Specifically, model II and model III were built on participants aged 20 to 59 years. Missing data was not included in the analyses. For all ORs reported, statistical significance was considered as CI not crossing 1 and corresponding p-value being less than 0.05.
R programming (RStudio, version 3.6) was used for all analyses. Library “tidyverse” was used to clean data and generate appropriate subset for statistical analyses. Library “survey” and “srvyr” were used to analyze weighted NHANES data. Survey functions “svytotal”, “svymean”, “svychisq” and “svyCreateTableOne” were used to perform descriptive analyses; “svyglm” was used to perform logistic regression modeling.
Overall, 50,588 people participated in NHANES surveys from 2007 to 2016, of whom 1,878 participants who failed to complete medical exams and 23,799 participants who were younger than 18 or over 69 years of age were excluded. There were 24,911 participants eligible to answer the question “ever using cocaine, heroin, or methamphetamine” of whom 3,399 (13.6%) participants did not respond to this question. Participants with missing values were more likely to be female, younger in age, and belonging to other races. There were 1,283 participants who reported ever using methamphetamine, and among them 18.4% had HBV vaccine-induced immunity. After further excluding those with HBV vaccine-induced immunity and with no blood-borne infections (n = 208), 1,075 participants were eligible (Fig. 1) with 157 (14.6%) diagnosed with blood-borne infections and 918 (85.4%) susceptible to blood-borne infections. The number of participants infected by HBV, HCV and HIV were 95 (61%), 93 (59%), and 11 (7%), respectively. Additionally, among these infected by any blood-borne viruses, 6 were infected by both HIV and HBV, 36 were infected by both HBV and HCV, and no one was infected by both HCV and HIV. Table 1 summarizes the frequencies and weighted estimates for factors associated with blood-borne infections. Based on the weighted estimates, the 1,075 participants represented approximately 11,319,270 methamphetamine users in the U.S. population with the overall prevalence of blood-borne infections at 13.4 per 100,000. Specifically, the prevalence of infection by HBV, HCV and HIV were 7.1, 7.8 and 1.1 per 100,000, respectively.
In the study sample, a third of the participants were female, about two thirds (64%) were non-Hispanic white, 25% of the participants were 50 to 59 years old and they accounted for 41% of blood-borne virus infections. Approximately, a quarter (23%) of the participants were living below the poverty threshold and they accounted for 35% of blood-borne infections; another 28% were living between 1 to 1.9 times poverty index and they accounted for 30% of blood-borne infections. A third of the participants did not have any health insurance, and nearly a quarter (23%) did not have routine healthcare access. About 30% of the participants with blood-borne virus infections had less than high school education. -About 2% were identified as men who had sex with men (MSM) and they accounted for 9% of blood-borne infections. While only 19% of methamphetamine users also reported ever using the other two drugs (heroin or cocaine), they accounted for over half (52%) of blood-borne infections. The majority of methamphetamine users did not inject any drugs (78%); however, almost two thirds (65%) of blood-borne infections were among the 22% of persons with IDU. Approximately 44% of participants first started using methamphetamine at age 18 to 25, and 22% between 10 and 17 years, and another 22% when they were older than 25 years.
Table 2 summarizes the estimated model effects (uOR and aOR with 95% CIs) of factors associated with the outcome variable. From bivariate analysis, being 50 to 59 years old (uOR 3.98; 95% CI 1.14–13.91), being 60 to 69 years old (4.05; 1.34–12.22), being non-Hispanic black (2.07; 1.15–3.71), living around poverty index 1 to 1.9 (2.07; 1.17–3.67), living below the poverty threshold (3.02; 1.66–5.49), having lower than high school education (2.23; 1.31–3.81), identified as MSM (17.45; 5.39–56.55), using methamphetamine with other two substances (5.93; 2.50–14.05), IDU (6.36; 3.84–10.54), having used methamphetamine more than 50 times (2.69; 1.39–5.24), and started using methamphetamine at age over 26 (2.05; 1.16–3.61) were statistically significantly associated with blood-borne infections among people who reported using methamphetamine.
The three-step multivariable logistic regression models further adjusted for all the covariates sequentially. The effect size of all aORs with 95% CIs are illustrated in Fig. 2. In model 1, only being older than 50 was significantly associated with blood-borne infections. After adding socio-economic status and sexual activities into model 2, there were significant associations of blood-borne infections with age 50–59 years old (aOR 8.94; 95% CI 2.09–38.26), living around poverty index 1 to 1.9 (2.89; 1.45–5.77), living below the poverty threshold (3.78; 1.61–8.90), having lower than high school education (3.24; 1.60–6.57), and identified as MSM (25.25; 6.78–94.00). In the final model 3, after adding drug use behaviors, associations of the same risk factors with blood-borne infections persisted: age 50–59 years old (6.32; 1.35–29.69), living around poverty index 1 to 1.9 (2.80; 1.33–5.88), living below the poverty threshold (2.46; 1.14–5.28), having lower than high school education (3.57; 1.74–7.33), and identified as MSM (54.24; 13.80–213.24). In addition, in this model, using methamphetamine with other two substances (5.86; 1.50–22.87), IDU (3.77; 1.93–7.36), and started using methamphetamine at age over 25 (2.18; 1.05–4.54) were also significantly associated with blood-borne infections.
Findings from our study using 10 consecutive years of NHANES data suggest that polysubstance use, IDU, and men who have sex with men were strongly associated with increased risk of blood-borne infections among methamphetamine users. Compared with people who were susceptible to blood-borne infections, those exposed to HBV, HCV or HIV were largely older, living two times below poverty index, having less than high school education, men who had sex with men, having ever used all three illicit drugs including methamphetamine, heroin and cocaine, injection drug users, and having started using methamphetamine at age over 25. Our study results corroborate with findings from previous literature that people who use methamphetamine have an elevated risk of infection of blood-borne viruses through sexual risk (MSM) and injecting risk [10, 30, 31].
Studies examining polysubstance use and their associations with harmful health effects are usually conducted at a smaller scale and among high-risk populations because of the challenges in capturing such information [22]. Using latent class analysis, studies have illustrated greater occurrence of sexual risk behaviors and increased diagnoses of blood-borne virus infections [32]. Findings from our large study using nationally representative data corroborate results from previous smaller studies that individuals with polysubstance use (i.e., co-ingestion or sequential use of methamphetamine with heroin, fentanyl or cocaine) have a higher likelihood of blood-borne infections.
Our study results suggest that persons who started using methamphetamine at age over 25 were more likely to be diagnosed with infections from blood-borne viruses. In a study assessing the effect of age and HIV status on methamphetamine use, the authors concluded that older persons without HIV were using methamphetamine at higher levels and were, therefore, at an increased risk of HIV [12]. More informed knowledge about risky behaviors among more vulnerable age-groups can provide guidance to tailor treatment strategies.
A recent study concluded that women using methamphetamine were four times as likely to be exposed to HBV infection as males [13]. While our study did not find sex to be associated with overall blood-borne infections, similar to that study’s result, we also did not find an association between number of past year sexual partners and blood-borne infections.
There are potential limitations associated with this study. Firstly, NHANES participants do not include incarcerated or homeless individuals, who have a higher rate of methamphetamine use than usual population. This may affect the generalizability of conclusion to the entire US adult population. Secondly, for sexual identity, we coded any men who had sex with men and men who had male sex partners last year as “MSM”, and the remaining any heterosexual as “heterosexual”, leaving female homosexual and other sexual identities as “other”. This recoding method may be different from others and affect the generalizability of our results. Thirdly, questions about illicit drug use and sexual behavior are sensitive in nature, thus, people might refuse to respond or be unwilling to respond honestly to those questions, leading to incorrect estimates. Fourthly, fentanyl and fentanyl analogs have contaminated American’s illicit drug supply, especially heroin. Participants may not be aware of the presence of fentanyl or fentanyl analogs in their methamphetamine or heroin product, resulting in incorrect estimate of self-reported number of drug use. So, polysubstance use is likely to be an underestimate in our study.
In conclusion, as methamphetamine use, especially polysubstance use including methamphetamine, continues to increase, it is of great public health importance to identify those vulnerable populations who are prone to be infected by blood-borne viruses. The results of the study are expected to provide evidence to inform timely harm reduction efforts to identify this population and target vaccination and interventions to prevent transmission. Prevention and intervention efforts targeted toward these specific subgroups can help alleviate fatal and nonfatal harms caused by methamphetamine use. In addition, an evolving polysubstance use landscape indicates a need for a rapid, multifaceted approach to incorporate more comprehensive surveillance efforts to inform effective prevention and response strategies to prevent blood-borne infection outbreak.
Ethics approval and consent to participate
Not applicable
Consent for publication
Not applicable
Competing interests
No conflict declared.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Authors' contributions
YC and ZD formulated the research question and designed the study. YC conducted all statistical analyses and SW provided statistical expertise. YC drafted the methods and results sections, ZD drafted the introduction and part of the discussion section, and RB completed the discussion section. RB also provided critical comments and valuable suggestions to the study. All authors had full access to all of the data and approved the final manuscript.
Acknowledgements
The authors would like to thank Dr. Casey Jelsema for his help on R codes.
Acquired Immunodeficiency Syndrome; aOR:Adjusted odds ratio; CDC:Centers for Disease Control and Prevention; CI:Confidence interval; HBsAb:Hepatitis B surface antibody; HBsAg:Hepatitis B surface antigen; HBV:Hepatitis B virus; HCV:Hepatitis C virus; HIV:Human immunodeficiency virus; IDU:Injection drug use; NCHS:National Center for Health Statistics; NHANES:National Health and Nutrition Examination Survey; MSM:Men who had sex with men; uOR:Unadjusted odds ratio.
https://doi.org/10.1097/QAI.0000000000000888.
https://doi.org/10.15585/mmwr.mm6806a4.