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. Author manuscript; available in PMC: 2015 Nov 1.
Published in final edited form as: Drug Alcohol Depend. 2014 Aug 29;144:87–92. doi: 10.1016/j.drugalcdep.2014.08.013

Pain is Associated with Risky Drinking over Time among HIV-Infected Persons in St. Petersburg, Russia

Judith I Tsui 1, Debbie M Cheng 1,2, Sharon M Coleman 3, Marlene C Lira 4, Elena Blokhina 5, Carly Bridden 4, Evgeny Krupitsky 5,6, Jeffrey H Samet 1,7
PMCID: PMC4252482  NIHMSID: NIHMS629828  PMID: 25220898

Abstract

Background

Pain is highly prevalent among persons with HIV. Alcohol may be used to “self-medicate” pain. This study examined the association between pain and risky alcohol use over time in a cohort of HIV-infected Russian drinkers.

Methods

This secondary analysis utilized longitudinal data from a randomized trial of a behavioral intervention. Subjects included HIV-infected adults who reported past 6-month risky drinking and unprotected sex and were recruited from HIV and addiction treatment sites in St. Petersburg, Russia. The main independent variable was pain that at least moderately interfered with daily living. The primary outcome was past month risky drinking amounts based on NIAAA guidelines. General estimating equations (GEE) logistic regression models were used to calculate odds ratios and 95% confidence intervals for the association between pain and risky drinking over time (i.e., baseline, 6- and 12-months), adjusting for potential confounders.

Results

Baseline characteristics of participants (n=699) were mean age of 30 (SD±5) years, 41% female, and 22% < 9th grade education. Nearly one quarter (24%) had a CD4 cell count <200 cells/μ/l, and only 17% were on antiretroviral therapy. Nearly half (46%) reported at least moderate pain interference in the past month and 81% were drinking risky amounts. In adjusted longitudinal GEE models, pain was significantly associated with greater odds of reporting past month risky drinking (AOR=1.34, 95% CI: 1.05-1.71, p-value=0.02).

Conclusions

Among a cohort of HIV-infected Russian drinkers, pain that at least moderately interfered with daily living was associated with higher odds of reporting risky drinking amounts over time.

Keywords: risky alcohol use, pain, HIV, Russia

1. INTRODUCTION

Chronic pain and substance use, including alcohol use, frequently overlap (Morasco et al., 2011). Despite the fact that alcohol use disorders are the most common substance use disorders, there is relatively less research to explore relationships between pain and alcohol compared to opiates. Acute alcohol use is known to have analgesic properties, while alcohol withdrawal is associated with hyperalgesia in animal and human studies. As such, persons may use alcohol initially to “self-medicate” existing pain, but subsequently persist in a pattern of use to relieve alcohol-related pain and affective disorders (Egli et al., 2012).

Pain is a common clinical problem among persons living with human immunodeficiency virus (HIV). The prevalence of pain in clinical samples of HIV-infected persons ranges from 30 to 90% (Breitbart et al., 1996; Del Borgo et al., 2001; Fantoni et al., 1997; Larue et al., 1997; Lee et al., 2009; Martin et al., 1999; Merlin et al., 2012a; Miaskowski et al., 2011; Richardson et al., 2009; Vogl et al., 1999) and a national survey of HIV-infected persons living in the United States found that 67% reported pain in the past week (Dobalian et al., 2004). Little is known about the impact of pain on drinking behaviors in HIV-infected adults, despite the fact that heavy alcohol use is more common in this group than the general population (Galvan et al., 2002). Studies conducted in non-HIV infected persons have reported use of alcohol in response to pain (Brennan et al., 2005; Riley and King, 2009). In one study of HIV-infected men, pain was found to be significantly associated with illicit drug use and depression (Tsao et al., 2011). Because unhealthy alcohol use is related to HIV-related sexual and drug risk behaviors (Shuper et al., 2009; Wen et al., 2012), non-adherence to HIV medications (Arnsten et al., 2002; Azar et al., 2010; Chander et al., 2006; Cohn et al., 2011; Golin et al., 2002; Howard et al., 2002) and lack of viral suppression (Azar et al., 2010; Lucas et al., 2002; Palepu et al., 2003; Samet et al., 2007; Wu et al., 2011), understanding whether pain is associated with alcohol use is especially relevant in this population.

The HIV epidemic in the Russian Federation (Russia) continues to grow, with an estimated 1 million individuals infected in 2009 (Joint United Nations Programme on HIV/AIDS (UNAIDS), 2012), predominantly through injection drug use (Krupitsky et al., 2004; Niccolai et al., 2011; World Health Organization, 2005). Alcohol is the most widely abused of substances globally, and Russia in particular is among the nations with the highest prevalence of alcohol use disorders (Rehm et al., 2009). Important differences in the management of pain exist between the United States/Western Europe and Russia. Restrictive policies toward the medical use of opioids in Russia results in opioids being less frequently prescribed for pain (Ponizovsky et al., 2012). Given that opioids are not generally prescribed for treatment of pain, it is possible that HIV-infected patients in Russia with pain might turn to other substances to relieve their pain.

We undertook this study to explore the association between pain and risky drinking in a cohort of HIV-infected Russians with alcohol problems. We previously reported an association between pain and heroin use over time in this sample (Tsui et al., 2013). Although alcohol has weaker analgesic properties, it is legal and much more widely available. Therefore, we hypothesized that existence of pain that at least moderately interfered with daily living would be associated with increased odds of reporting risky drinking over time in this cohort.

2. METHODS

2.1. Study Design and Participants

We performed secondary analyses of longitudinal data from the HERMITAGE (HIV Evolution in Russia—Mitigating Infection Transmission and Alcoholism in a Growing Epidemic) study, a randomized controlled trial conducted that tested a secondary HIV prevention intervention (Pace et al., 2012). Participants were recruited from four inpatient and outpatient HIV and addiction care sites in St. Petersburg, Russia including: 1) Botkin Infectious Disease Hospital, 2) the St. Petersburg AIDS Center, 3) First St. Petersburg Pavlov State Medical University Clinics, and 4) the St. Petersburg State Drug Treatment Clinic between 2007 and 2010. Eligibility criteria included the following: HIV-infection; 18-70 years old; any risky drinking by National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria (National Institute on Alcohol Abuse and Alcoholism, 2005) in the past 6 months (i.e., drinking greater than 14 standard drinks per week/greater than 4 drinks in a day for men; greater than 7 drinks in the past week/greater than 3 drinks in a day for women); unprotected vaginal or anal sex in the past 6 months; provision of contact information of two relatives or close friends who could to assist with follow-up; stable address/telephone; fluency in Russian; and ability to provide informed consent. Exclusion criteria were anticipated incarceration or trying to conceive. The current study included only those subjects with at least baseline data on both pain and substance use measures. Of the 700 participants of the main study, one participant was excluded for this reason. Both the Institutional Review Boards of Boston Medical Center and First St. Petersburg Pavlov State Medical University approved this study.

2.2. Data Collection

After eligibility assessment, all participants provided written informed consent. Data were collected at baseline, 6 month and 12 month visits. Pain and substance use assessments were administered by interviewers at each visit. Interviews were conducted in Russian using translated tools.

2.3. Measures

2.3.1 Outcome Measure

The primary outcome of interest was a dichotomous variable of whether the participant reported past month consumption of risky amounts of alcohol based on NIAAA criteria (see above).

2.3.2 Main Predictor

The main predictor of interest was pain that at least moderately interfered with daily living in the past month (i.e., clinically significant pain), defined as. This was based on a single question from the Short Form-12 (SF-12) (Ware et al., 1996), which asks, “During the past month, how much did pain interfere with your normal work, including housework?”. The range of possible responses were “not at all/a little bit/moderately/quite a bit/extremely”, and responses were dichotomized at the threshold of “moderately” or above.

2.3.3 Covariates

Covariates included in the analysis as potential confounders were the following: age, marital status, gender, education (<9th grade), depressive symptoms, current use of illicit drugs, which included use of heroin, stimulants (cocaine, amphetamines and ephedrine) or cannabis, HCV status, recruitment site and randomization group. The two HIV-related recruitment sites were combined for the purpose of analyses. Covariates were chosen a priori based on prior literature and clinical knowledge. Depressive symptoms were assessed using the Beck Depression Inventory II (BDI- II) – Russian version and a threshold of 20 was used to define moderate to severe symptoms of depression (Beck, 1996). Use of illicit drugs in the past 30 days was assessed using the Risk Behavior Survey (Needle et al., 1995; Weatherby et al., 1994), which we modified for the Russian setting by asking about drugs commonly used in Russia.

2.4. Statistical Analysis

Descriptive statistics were used to characterize study subjects overall and by pain status at baseline. Those with and without clinically significant pain were also compared using chi-square and Student's t tests. Generalized estimating equations (GEE) logistic regression models were used to evaluate the association between reporting clinically significant pain in the past month and risky drinking in the past month at each assessment (i.e., baseline, 6- and 12-months). Odds ratios and 95% confidence intervals are reported for each model. The GEE approach was used to account for the correlation from using repeated observations from the same subject over time. The GEE approach uses all available data and allows for varying numbers of observations per participant. An independence working correlation structure was used, and empirical standard errors are reported for all analyses. Spearman correlation coefficients were calculated between independent variables and covariates, and no pair of variables had a correlation >0.40. Final models were adjusted for all covariates. Pain, illicit drug use, and depressive symptoms were modeled as time-dependent covariates; all other covariates (age, marital status, gender, education, HCV status, recruitment site and randomization group) were based on baseline values. For the primary analyses, only the observed data were used, missing data were not imputed. However, sensitivity analyses were conducted using multiple imputation to address missing follow-up data for the risky drinking outcome. Baseline variables used for the imputation were age, marital status, randomization group, education level, gender, depression, illicit drug use in the previous 30 days, recruitment site, HCV status, and previous drinking status. A sensitivity analysis that adjusted for each drug (heroin, stimulants and cannabis) separately rather than using a composite variable of illicit drug use was also conducted. Two-tailed tests and a significance level of 0.05 were used for all hypothesis testing.

3. RESULTS

At baseline, participants (n=699) had a mean age of 30 (SD±5) years, 41% were female, 22% had a less than 9th grade education and 36% were married/living with a partner. Approximately one quarter of the sample had a CD4 cell count less than 200, and only 17% were on ART. Nearly half (323/699; 46%) reported pain in the past month that at least moderately interfered with daily living; this subsequently decreased at later visits (183/523; 35% at 6 months and 173/492; 35% at 12 months). Among the sample of 567 that had at least 2 research assessments, 294 (52%) had moderate pain interference at ≥1 visit but not all visits, while 78 (14%) reported such pain at all visits. At baseline, 569/699 (81%) reported drinking risky amounts of alcohol and (47%) reported use of any illicit drugs in the past month. Heroin was the drug most often used (38%), followed by cannabis (21%) and stimulants (12%). The proportion reporting risky drinking amounts declined from baseline to 217/523 (42%) at 6 months and 198/492 (40%) at 12 months.

Table 1 describes overall characteristics of the cohort and differences at baseline between participants with and without pain that at least moderately interfered with daily living. Participants with pain were significantly more likely to be female (47% v. 35%, p<0.01) and have moderate to severe depressive symptoms (51% v. 34%, p<0.01). Individuals with moderate pain interference appeared more likely to have been infected with hepatitis C virus (84% v. 76%, p=0.06), and to have been infected with HIV for a longer duration (years of infection 4.6 [±3.6] v. 4.2 [±3.5], p=0.12) although neither difference was statistically significant.

Table 1.

Baseline Characteristics of HIV-infected Russians with Past 6-month Risky Drinking and Sex: Overall, and Stratified by Pain Status

Overall < Moderate Pain Interference ≥ Moderate Pain Interference p-value
(n=699) (n=376) (n=323)
Age (Mean ±SD) 30.1 (±5.2) 29.8 (±5) 30.4 (±5.5) 0.18
Female 41% 35% 47% <0.01
≥ 9th grade education 78% 79% 76% 0.37
Married or living with a partner 36% 34% 39% 0.16
Unemployed 27% 22% 33% <0.01
Recruitment site
    Pavlov Medical University 30% 35% 25% 0.04
    City Addiction Center 13% 12% 13%
    AIDS Clinics 57% 53% 62%
≥Moderate depressive symptoms* 42% 34% 51% <0.01
Past month risky drinking** 81% 80% 83% 0.32
HCV seropositive 80% 76% 84% 0.06
CD4 <350 cells/mm3 24% 21% 28% 0.26
Current ART 17% 17% 18% 0.82
Years with HIV(Mean ±SD) 4.4 (±3.6) 4.2 (±3.5) 4.6 (±3.6) 0.12
Lifetime heroin use 83% 81% 85% 0.11
Current illicit drug use† 47% 43% 51% 0.05
    heroin 38% 33% 44%
    stimulants 12% 10% 14%
    cannabis 20% 20% 21%
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*

Beck Depression Inventory II score ≥20

**

Based on NIAAA definition

†

Past month use of heroin, stimulants or cannabis

The longitudinal analysis included 1,710 observations from 699 participants. In unadjusted analyses shown in Table 2, moderate pain interference in the past month was associated with higher odds of reporting drinking risky amounts of alcohol during the same time frame (OR=1.40; 95% CI: 1.11 to 1.77, p=0.004). After adjustment for age, marital status, gender, education, depressive symptoms, study timepoint, illicit drug use, HCV status, recruitment site and randomization group, participants with moderate pain interference had approximately a 34% increased odds of reporting risky drinking amounts in the past month compared to those without pain (AOR=1.34; 95% CI: 1.05 to 1.71, p=0.02). In sensitivity analyses using multiple imputation to account for missing data on risky drinking, the results were similar (AOR 1.26, 95% CI 1.02-1.57; p=0.03). Adjustment for illicit drug use as separate covariates also did not appreciably change results for pain (AOR=1.38; 95% CI: 1.08-1.77; p=0.01).

Table 2.

Regression Models for Longitudinal Associations between Pain and Drinking Risky Amounts among HIV-infected Russians, Results from Generalized Estimating Equation (GEE) Models

Unadjusted OR (95% CI) p-value Adjusted OR (95% CI) p-value
≥Moderate Pain Interference 1.40 (1.11, 1.77) 0.004 1.34 (1.05, 1.71) 0.02
Baseline (ref) 1 <0.001 1 <0.001
6 months 0.17 (0.13, 0.21) 0.17 (0.13, 0.22)
12 months 0.16 (0.12, 0.20) 0.16 (0.12, 0.21)
Intervention 1.04 (0.81, 1.33) 0.73
Age (year) 0.99 (0.97, 1.01) 0.38
Male 1.67 (1.29, 2.16) <0.001
≥ 9th grade education 0.84 (0.63, 1.14) 0.27
Married or living with a partner 1.25 (0.96, 1.63) 0.09
≥ Moderate Depressive Symptoms* 0.94 (0.72, 1.23) 0.65
Current Illicit Drug Use** 2.04 (1.59, 2.62) <0.001
HCV-infected 0.83 (0.49, 1.38) 0.17
Site <0.001
    Pavlov Medical University 1
    City Addiction Center 0.70 (0.50, 0.98)
    AIDS Clinics 1.40 (1.06, 1.85)
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*

Beck Depression Inventory II score ≥20

**

Use of heroin, stimulants or cannabis

4. DISCUSSION

In this study of HIV-infected Russian drinkers, we found that self-reported pain that at least moderately interfered with daily living was associated with higher odds of reporting concurrent risky drinking, even after adjustment for potential confounders including illicit drug use. This study highlights the relationship between pain and alcohol use, which is particularly important in the setting of HIV, since risky drinking has been associated with higher sex and drug risk behaviors and worse antiretroviral medication adherence (Chander et al., 2006; Samet et al., 2004; Shuper et al., 2009; Wen et al., 2012).

Alcohol has analgesic effects, elevating pain tolerance in healthy volunteers (Perrino et al., 2008). However, withdrawal from alcohol is associated with increased pain sensitivity (Jochum et al., 2010). This suggests that management of pain with alcohol could eventually lead to greater pain, through a cyclic pattern of use. Given that opioids are infrequently prescribed in Russia and that alcohol use is highly prevalent and culturally sanctioned, it is plausible that HIV-infected person might “self-medicate’ their pain with alcohol. Surveys of adults without HIV in the United States have reported use of alcohol to self-medicate pain (Brennan et al., 2005; Riley and King, 2009), and problem drinkers are more likely to report these behaviors than non-problem drinkers (Brennan et al., 2005). While to our knowledge, no studies have directly assessed this in HIV-infected persons or in Russia (or HIV-uninfected persons in Russia), a Russian study of premature deaths related to alcohol noted that alcohol use was used for pain and other ailments (Saburova et al., 2011).

Chronic pain is also a major stressor, which can increase vulnerability to substance use and dependence (Uhart and Wand, 2009). Exposure to aversive life conditions was previously found to be cross-sectionally associated with problematic drinking among a random sample of adult residents in Moscow (Zvolensky et al., 2005). Furthermore, a qualitative study of stress and health among adults in St. Petersburg identified alcohol use as a commonly cited coping mechanism among males (Pietila and Rytkonen, 2008). A longitudinal study in the United States found that baseline reporting of drinking to cope was associated with subsequent drinking problems (Holahan et al., 2001), and among persons being treated for substance use disorders, persistent pain has been associated with a lower likelihood of being abstinent of alcohol or drugs in the future (Caldeiro et al., 2008; Larson et al., 2007). Because opioids are not typically prescribed for chronic pain management in Russia (Ponizovsky et al., 2012), it is conceivable that persons with pain might be more likely to turn to a legal, culturally sanctioned substance like alcohol to treat pain and pain-related stress. Effective pain management services may prove useful to reduce unforeseen consequences like unhealthy alcohol use among HIV-infected persons.

Less is known about the relationships between pain and alcohol use specifically among HIV infected persons. A study of 1,940 HIV-infected men in the United States found that pain was significantly associated with cannabis and hard drug use defined as cocaine or heroin use (Tsao et al., 2011), and we previously reported an association between pain and heroin use in this same Russian sample (Tsui et al., 2013). A prior study conducted in a population of homeless, HIV-infected persons in San Francisco that examined bivariate associations between substance use and pain severity did not find differences in the proportion reporting current daily drinking among pain severity categories (Miaskowski et al., 2011). Similarly, a clinic-based sample of 162 HIV-infected persons with psychological and substance use disorders in the United States found no associations between presence of alcohol use disorders and bodily pain based on the SF-36 (Tsao and Soto, 2009). Our study, in contrast, supports the growing body of literature demonstrating the effect of pain on substance use patterns over time in HIV-infected men and women by demonstrating that pain is associated in with increased odds of risky drinking over time. This is particularly relevant as heavy drinking is associated with HIV sex and drug risk behaviors (Shuper et al., 2009; Wen et al., 2012), worse medication adherence and a myriad of adverse health effects (osteopenia, liver disease, neurocognitive impairment). In addition, among HIV-infected persons, pain itself has been associated with non-adherence to ART (Berg et al., 2009) and clinic appointments (Merlin et al., 2012b), a relationship that may perhaps be mediated through increased unhealthy alcohol use. It is worth noting that the majority of participants in this study were also infected with hepatitis C, for which alcohol greatly enhances the risk of developing liver complications (e.g., cirrhosis, liver cancer) (Bhattacharya and Shuhart, 2003; Hutchinson et al., 2005). Therefore, this study, which reveals an association between pain and risky alcohol use, provides information relevant toward improving the health of persons with HIV and preventing further transmission of this disease.

This study had limitations. Clinically significant pain was based on a single question from the SF-12; we did not have additional information on pain severity, duration, causes (such as recent illness) or treatment. However, other studies similarly have utilized single question responses from health-related quality of life instruments to define pain (Caldeiro et al., 2008; Larson et al., 2007). Although we adjusted for use of illicit drugs, including marijuana which has known analgesic properties, our methods for defining use (any versus none) could allow for residual confounding. The study questionnaire did not specifically ask participants whether they used alcohol to self-treat their pain. We hypothesized that the observed association between pain and drinking risky amounts of alcohol was in part due to participants’ efforts to self-medicate, however it is also plausible that drinking risky amounts of alcohol could lead to pain. Alcohol withdrawal is associated with increased sensitivity to pain (hyperalgesia) in animal and human studies (Edwards et al., 2012; Jochum et al., 2010). Chronic alcohol use may lead to painful comorbidities such as peripheral neuropathy and trauma-related injuries. Research suggests shared central neural pathways between alcohol dependence and chronic pain (Egli et al., 2012). Finally, alcohol has profound effects on the immune system and levels of pro-inflammatory cytokines (Crews et al., 2006; Szabo and Mandrekar, 2009; Wang et al., 2012), which also have been implicated in the generation of chronic pain states (DeVon et al., 2014; Watkins and Maier, 2005). Thus, it is likely that the relationship between pain and alcohol use may be complex and bi-directional.

In summary, we found that pain that at least moderately interfered with daily living was associated with increased odds of drinking risky amounts of alcohol among HIV-infected persons in Russia. Given that risky drinking is associated with HIV-risk behaviors and adverse health outcomes, the importance of pain and appropriate pain management should not be overlooked by clinicians and those involved in health policy. More research is needed on alcohol use as a coping behavior for pain among persons with HIV, and the effects of long-term alcohol use on risk for pain.

Highlights.

  • This study examined the association between pain and risky alcohol use over time in a cohort of HIV-infected Russian drinkers.

  • Nearly half (46%) reported at least moderate pain interference in the past month and 81% were drinking risky amounts.

  • Patients who reported at least moderate pain interference were more likely to report risky drinking over time.

Acknowledgments

Role of Funding Source:

The project described was supported by award numbers R01AA016059, U24AA020778, U24AA020779, and K24AA015674 from the National Institute on Alcohol Abuse and Alcoholism and award numbers K23DA027367 and R01DA013582 from the National Institute on Drug Abuse. The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Footnotes

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Contributors:

Samet, Krupitsky, Blokhina and Bridden are responsible for the acquisition of data. Tsui, Samet and Cheng are responsible for the study concept and design. Coleman and Cheng undertook the statistical analysis. Tsui and Lira managed the literature searches and summaries of previous related work and drafted the manuscript. All authors provided contributed to the interpretation of data and critical revisions of the manuscript. All authors have approved the final manuscript.

Conflicts of Interest: The authors do not declare financial conflicts of interest.

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