Jeffrey H. Samet

Acute Pain Management for Patients Receiving Maintenance Methadone or Buprenorphine Therapy

The treatment of opioid dependence, both on heroin and prescription narcotics, with opioid agonist therapy (OAT) (that is, methadone or buprenorphine) is effective: It decreases opioid and other drug abuse, increases treatment retention, decreases criminal activity, improves individual functioning, and decreases HIV seroconversion (1-5). Because of the increasing use of these medications for prolonged periods in primary care, a practice called office-based opioid treatment, nonaddiction specialists will be treating more of these affected patients in clinical practice, including those with episodes of acute pain (6-11). Adequate treatment of acute painful conditions is an essential dimension of quality medical care (12-17). Inadequate treatment is common among a wide spectrum of patients (18-23). Nonopioid analgesics (for example, nonsteroidal anti-inflammatory drugs and acetaminophen) are recommended for treating acute pain; however, moderate to severe acute pain will often require opioid analgesics (24). Physicians may not prescribe effective opioid analgesia across all patient populations because of fears of cognitive, respiratory, and psychomotor side effects; iatrogenic drug addiction; and prescription drug diversion (25, 26). This tendency of health care professionals to undermedicate patients with opioid analgesics has been termed opiophobia (27). Such fears are exaggerated when treating patients with a known history of a substance use disorder. The provision of opioid analgesics to a patient with opioid dependence receiving OAT can be particularly challenging (28, 29). We highlight the issues associated with the management of acute pain in patients receiving OAT and describe theoretical and empirical findings that suggest unique requirements for opioid analgesia for such patients. In addition, we identify common misconceptions of health care providers that underlie inadequate pain management and provide practical recommendations for the analgesic management of acute pain in this special clinical population. To help illustrate these issues, we present the following clinical vignette from our experience. A 29-year-old woman reported severe right arm pain after fracturing her olecranon process. She had a history of injection heroin use and received methadone, 90 mg/d, in a methadone maintenance program. In the emergency department, she seemed uncomfortable and received one 2-mg dose of intramuscular morphine sulfate over 6 hours. While hospitalized, she continued to report severe pain despite receiving her daily methadone dose and intramuscular ketorolac. She was told that her usual methadone dose should help control her pain. She was labeled as drug-seeking because of her constant requests for additional pain medications. Pain and Opioid Dependence The clinical conditions of pain and opioid dependence are not unrelated phenomena (30-32). Forty-one years ago, Martin and Inglis (33) observed that opioid-addicted patients abuse opioids to treat an abnormally low tolerance for painful stimuli. Opioids, whether administered with analgesic or addictive intent, activate opiate receptors in the locus coeruleus and amygdala, which provide both analgesia and reward (34, 35). The presence of one condition seems to influence the expression of the other. Clinical examples of this include how the presence of acute pain seems to decrease the euphorogenic (pleasurable) qualities of the opioid (36) and how the presence of addictive disease seems to worsen the experience of pain. With respect to the latter, Savage and Schofferman (37) found a decade ago that persons with addiction and pain have a syndrome of pain facilitation. Their pain experience is worsened by subtle withdrawal syndromes, intoxication, withdrawal-related sympathetic nervous system arousal, sleep disturbances, and affective changes, all consequences of addictive disease (37). Supporting a negative effect of addiction on pain tolerance, patients who abuse stimulants and those who abuse opioids have been shown to be less tolerant of pain than their peers in remission (38, 39). The clinical approach is complicated by the confusing and often misunderstood terminology used in pain management and addiction medicine (40-43). As detailed in Table 1, physical dependence and tolerance are typical and predictable physiologic consequences of opioid exposure. These terms in and of themselves do not indicate maladaptive behaviors and do not meet the diagnostic criteria of substance dependence (41) outlined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision, without, for example, loss of control or continued use despite harm. Drug-seeking is another commonly ill-defined term that may indicate the presence of addiction but, as will be described, can also reflect pain reliefseeking because of unrelieved pain or anxiety about pain management (44). Table 1. Pain and Addiction Terminology Common Misconceptions Four common misconceptions of health providers result in the undertreatment of acute pain in patients receiving OAT: 1) The maintenance opioid agonist (methadone or buprenorphine) provides analgesia; 2) use of opioids for analgesia may result in addiction relapse; 3) the additive effects of opioid analgesics and OAT may cause respiratory and central nervous system (CNS) depression; and 4) the pain complaint may be a manipulation to obtain opioid medications, or drug-seeking, because of opioid addiction. Misconception 1: The Maintenance Opioid Agonist (Methadone or Buprenorphine) Provides Analgesia There are pharmacokinetic and pharmacodynamic explanations for why patients do not receive adequate analgesia from maintenance opioids prescribed for addiction treatment. Not only do the analgesic and addiction treatment profiles of these opioids differ, but the neuroplastic changes associated with long-term opioid exposure (that is, tolerance and hyperalgesia) may effectively diminish their analgesic effectiveness (45). Analgesic Properties of Maintenance Opioids Patients receiving maintenance therapy with opioids for addiction treatment do not derive sustained analgesia from it. Methadone and buprenorphine, potent analgesics, have a duration of action for analgesia (4 to 8 hours) that is substantially shorter than their suppression of opioid withdrawal (24 to 48 hours) (46-50). Because most patients receiving OAT are given a dose every 24 to 48 hours, the period of even partial pain relief with these medications is small. Opioid Tolerance Tolerance is one factor that explains why these patients derive little pain relief from maintenance opioids. Tolerance, the need for increasing doses of a medication to achieve its initial effects, develops with continuous opioid use but differentially affects specific opioid properties. For example, tolerance readily develops to the respiratory and CNS depressive effects of opioids but not to their constipating effects (51, 52). Analgesic tolerance develops for different medications within the opioid class, a phenomenon called cross-tolerance (53, 54). Doverty and colleagues (55) found that patients receiving maintenance methadone therapy were cross-tolerant to the analgesic effects of morphine and that pain relief, when obtained, did not last as long as expected. Therefore, cross-tolerance between the opioids used for maintenance therapy and other opioids used for analgesia may explain why patients receiving OAT often require higher and more frequent doses of opioid analgesics to achieve adequate pain control. Opioid-Induced Hyperalgesia An alternative explanation for the lack of analgesia derived from maintenance opioids may be the presence of opioid-induced hyperalgesia. This is the result of neuroplastic changes in pain perception that yield an increase in pain sensitivity. The outcome is that opioids have less potent analgesic effects (45, 56-58). Empirical evidence supports increased sensitivity to experimental pain in patients receiving OAT (33, 38, 55, 59-62), such that patients receiving maintenance methadone therapy tolerate cold-pressor pain only half as long as do matched controls (55, 59). Accumulating evidence suggests that maintenance with buprenorphine therapy has similar and statistically significant effects on pain tolerance, although to a lesser degree than methadone (63). The pain intolerance of patients receiving methadone and buprenorphine maintenance therapy can be conceptualized as a latent hyperalgesia secondary to long-term opioid exposure. The presence of hyperalgesia with ongoing opioid use has resulted in reexamination of the previously described phenomenon of opioid analgesic tolerance. Both hyperalgesia and opioid tolerance involve neuroplastic changes associated with excitatory amino acid (N-methyl-d-aspartate) and opioid receptors (64-70). The hyperalgesic processes precipitated by opioid administration serve to counteract opioid analgesia (56, 71-73); thus, it is possible that what seems to be opioid analgesic tolerance may in fact be an expression of an opioid-induced increased sensitivity to pain. Therefore, despite the benefits of OAT for the opioid-dependent person, the accompanying hyperalgesia (or analgesic tolerance) counteracts the analgesic effects of opioids and complicates pain management. At clinically effective doses for the treatment of opioid dependence, patients do not experience analgesia to experimental pain but demonstrate the hyperalgesic effects of OAT. Thus, from a theoretical and experimental basis, it is clear that the perception of pain is not decreased in OAT patients. Misconception 2: Use of Opioids for Analgesia May Result in Addiction Relapse A common concern of physicians is that the use of opioids for analgesia in patients receiving OAT May result in relapse to active drug use. However, there is no evidence that exposure to opioid analgesics in the presence of acute pain increases rates of relapse in such patients. A small retrospectiv

Understanding delay to medical care for HIV infection : the long-term non-presenter

ObjectiveTo examine delayed presentation for HIV testing and primary care in the second decade of the AIDS epidemic. DesignCohort study in two urban hospitals in the USA between February 1994 and April 1996. MethodsA total of 203 consecutive outpatients on initial HIV primary care presentation were interviewed about sociodemographic characteristics, alcohol and drug use, social support, sexual practices, HIV testing, awareness of possible HIV infection, and CD4 cell count. Main outcome measureDuration of delay to medical presentation in years based on CD4 cell count, factors independently associated with low CD4 cell counts, frequency of awareness of HIV risk before testing. ResultsThe estimated mean duration between acquiring HIV infection and initial presentation to primary care was 8.1 years (95% CI 7.5, 8.6) based on our cohorts median initial CD4 cell count of 280/μl. Male sex, older age, and no jail time were associated with lower CD4 cell counts; 34% reported not being aware that they were at risk of HIV before testing. Heterosexual intercourse as a risk behavior for HIV was the most statistically significant factor for personal unawareness of HIV risk. Of those who acknowledged awareness, the mean time between awareness of HIV risk and testing was 2.5 years (median 1.0 year). ConclusionIn the pre-highly active antiretroviral therapy era, HIV-infected patients frequently initiated primary medical care years after initial infection, at a time of advanced immunosuppression. Over one-third of HIV-infected patients were not cognisant of their HIV risk before testing, a condition significantly associated with heterosexual intercourse as the only HIV risk behavior.

Alcohol Consumption and HIV Disease Progression

Objective:To assess the relation between alcohol consumption and laboratory markers of HIV disease progression. Methods:We prospectively assessed CD4 cell counts, HIV RNA levels, and alcohol consumption for up to 7 years in 595 HIV-infected persons with alcohol problems recruited between 1997 and 2003. We investigated the relation of these markers of HIV disease progression to alcohol consumption using longitudinal regression models controlling for known prognostic factors, including adherence and depressive symptoms, and stratified by antiretroviral therapy (ART) use. Results:Among subjects who were not on ART, heavy alcohol consumption was associated with a lower CD4 cell count (adjusted mean decrease of 48.6 cells/μL compared with abstinence; P = 0.03) but not with higher log10 HIV RNA. Among subjects who were on ART, heavy alcohol consumption was not associated with a lower CD4 cell count or higher log10 HIV RNA. Conclusions:Heavy alcohol consumption has a negative impact on the CD4 cell count in HIV-infected persons not receiving ART. In addition to the known deleterious effects of alcohol on ART adherence, these findings suggest that avoiding heavy alcohol consumption in patients not on ART may have a beneficial effect on HIV disease progression.

Screening and brief intervention for drug use in primary care: the ASPIRE randomized clinical trial.

IMPORTANCE The United States has invested substantially in screening and brief intervention for illicit drug use and prescription drug misuse, based in part on evidence of efficacy for unhealthy alcohol use. However, it is not a recommended universal preventive service in primary care because of lack of evidence of efficacy. OBJECTIVE To test the efficacy of 2 brief counseling interventions for unhealthy drug use (any illicit drug use or prescription drug misuse)-a brief negotiated interview (BNI) and an adaptation of motivational interviewing (MOTIV)-compared with no brief intervention. DESIGN, SETTING, AND PARTICIPANTS This 3-group randomized trial took place at an urban hospital-based primary care internal medicine practice; 528 adult primary care patients with drug use (Alcohol, Smoking, and Substance Involvement Screening Test [ASSIST] substance-specific scores of ≥4) were identified by screening between June 2009 and January 2012 in Boston, Massachusetts. INTERVENTIONS Two interventions were tested: the BNI is a 10- to 15-minute structured interview conducted by health educators; the MOTIV is a 30- to 45-minute intervention based on motivational interviewing with a 20- to 30-minute booster conducted by masters-level counselors. All study participants received a written list of substance use disorder treatment and mutual help resources. MAIN OUTCOMES AND MEASURES Primary outcome was number of days of use in the past 30 days of the self-identified main drug as determined by a validated calendar method at 6 months. Secondary outcomes included other self-reported measures of drug use, drug use according to hair testing, ASSIST scores (severity), drug use consequences, unsafe sex, mutual help meeting attendance, and health care utilization. RESULTS At baseline, 63% of participants reported their main drug was marijuana, 19% cocaine, and 17% opioids. At 6 months, 98% completed follow-up. Mean adjusted number of days using the main drug at 6 months was 12 for no brief intervention vs 11 for the BNI group (incidence rate ratio [IRR], 0.97; 95% CI, 0.77-1.22) and 12 for the MOTIV group (IRR, 1.05; 95% CI, 0.84-1.32; P = .81 for both comparisons vs no brief intervention). There were also no significant effects of BNI or MOTIV on any other outcome or in analyses stratified by main drug or drug use severity. CONCLUSIONS AND RELEVANCE Brief intervention did not have efficacy for decreasing unhealthy drug use in primary care patients identified by screening. These results do not support widespread implementation of illicit drug use and prescription drug misuse screening and brief intervention. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00876941.

Assessing missed opportunities for HIV testing in medical settings

BACKGROUND: Many HIV-infected persons learn about their diagnosis years after initial infection. The extent to which missed opportunities for HIV testing occur in medical evaluations prior to one’s HIV diagnosis is not known. DESIGN: We performed a 10-year retrospective chart review of patients seen at an HIV intake clinic between January 1994 and June 2001 who 1) tested positive for HIV during the 12 months prior to their presentation at the intake clinic and 2) had at least one encounter recorded in the medical record prior to their HIV-positive status. Data collection included demographics, clinical presentation, and whether HIV testing was recommended to the patient or addressed in any way in the clinical note. Prespecified triggers for physicians to recommend HIV testing, such as specific patient characteristics, symptoms, and physical findings, were recorded for each visit. Multivariable logistic regression was used to identify factors associated with missed opportunities for discussion of HIV testing. Generalized estimating equations were used to account for multiple visits per subject. RESULTS: Among the 221 patients meeting eligibility criteria, all had triggers for HIV testing found in an encounter note. Triggers were found in 50% (1,702/3,424) of these 221 patients’ medical visits. The median number of visits per patient prior to HIV diagnosis to this single institution was 5; 40% of these visits were to either the emergency department or urgent care clinic. HIV was addressed in 27% of visits in which triggers were identified. The multivariable regression model indicated that patients were more likely to have testing addressed in urgent care clinic (39%), sexually transmitted disease clinic (78%), primary care clinics (32%), and during hospitalization (47%), compared to the emergency department (11%), obstetrics/gynecology (9%), and other specialty clinics (10%) (P<.0001). More recent clinical visits (1997–2001) were more likely to have HIV addressed than earlier visits (P<.0001). Women were offered testing less often than men (P=.07). CONCLUSIONS: Missed opportunities for addressing HIV testing remain unacceptably high when patients seek medical care in the period before their HIV diagnosis. Despite improvement in recent years, variation by site of care remained important. In particular, the emergency department merits consideration for increased resource commitment to facilitate HIV testing. In order to detect HIV infection prior to advanced immunosuppression, clinicians must become more aware of clinical triggers that suggest a patient’s increased risk for this infection and lower the threshold at which HIV testing is recommended.

Office-Based Management of Opioid Dependence with Buprenorphine: Clinical Practices and Barriers

BackgroundBuprenorphine is a safe, effective and underutilized treatment for opioid dependence that requires special credentialing, known as a waiver, to prescribe in the United States.ObjectiveTo describe buprenorphine clinical practices and barriers among office-based physicians.DesignCross-sectional survey.ParticipantsTwo hundred thirty-five office-based physicians waivered to prescribe buprenorphine in Massachusetts.MeasurementsQuestionnaires mailed to all waivered physicians in Massachusetts in October and November 2005 included questions on medical specialty, practice setting, clinical practices, and barriers to prescribing. Logistic regression analyses were used to identify factors associated with prescribing.ResultsPrescribers were 66% of respondents and prescribed to a median of ten patients. Clinical practices included mandatory counseling (79%), drug screening (82%), observed induction (57%), linkage to methadone maintenance (40%), and storing buprenorphine notes separate from other medical records (33%). Most non-prescribers (54%) reported they would prescribe if barriers were reduced. Being a primary care physician compared to a psychiatrist (AOR: 3.02; 95% CI: 1.48–6.18) and solo practice only compared to group practice (AOR: 3.01; 95% CI: 1.23–7.35) were associated with prescribing, while reporting low patient demand (AOR: 0.043, 95% CI: 0.009–0.21) and insufficient institutional support (AOR: 0.37; 95% CI: 0.15–0.89) were associated with not prescribing.ConclusionsCapacity for increased buprenorphine prescribing exists among physicians who have already obtained a waiver to prescribe. Increased efforts to link waivered physicians with opioid-dependent patients and initiatives to improve institutional support may mitigate barriers to buprenorphine treatment. Several guideline-driven practices have been widely adopted, such as adjunctive counseling and monitoring patients with drug screening.

Brief intervention for medical inpatients with unhealthy alcohol use: a randomized, controlled trial

Context Brief interventions reduce alcohol use in outpatients who drink unhealthy amounts but are not alcohol-dependent. Their effect in medical inpatients is unknown. Contribution The authors screened all adult medical inpatients at an urban teaching hospital and randomly assigned 341 risky drinkers to a 30-minute motivational counseling intervention followed gy treatment planning or to usual care. By 3 months, the same proportion of patients from both groups had received alcohol assistance, and both groups had reduced their drinking to the same degree. Cautions Three quarters of the participants met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence. Implications In this well-done study, brief intervention did not affect alcohol-related outcomes in persons who drank unhealthy amounts. The Editors Professional organizations recommend that clinicians screen their patients for unhealthy alcohol use (that is, the spectrum from drinking risky amounts to dependence) and conduct a brief intervention when indicated (1, 2). Despite this recommendation and the existence of brief, valid screening tools (35), patients with unhealthy alcohol use often are not identified and do not receive timely care. Although widely recommended, brief intervention has proven efficacy in decreasing alcohol consumption and related consequences only in unhealthy drinkers without alcohol dependence and in outpatient settings (6). Its efficacy among other populations (for example, persons with alcohol dependence) and in inpatient settings remains unclear (7). Evidence suggests, however, that medical inpatientsa group with a high prevalence of alcohol-related problemsmay benefit from brief intervention. Some studies have demonstrated the efficacy of brief intervention in settings similar to medical services in which alcohol-related problems are common and their related consequences are severe (8, 9). Further, brief interventions are well suited to medical services. Patients who otherwise might not seek care are accessible and have time for an intervention. Persons admitted because of an alcohol-related problem may recognize the link between drinking and hospitalization, thus providing a teachable moment (10). Also, busy staff might implement a brief intervention because of its brevity and flexibility. The unmet need for alcohol screening and intervention and opportunities for implementation underscore the importance of determining the efficacy of brief intervention in medical inpatients with unhealthy alcohol use. In addition, evaluating its effectiveness and practicality in real-world settings is critical to help clinicians make informed decisions when treating their patients (11). Therefore, we conducted a randomized, controlled trial to examine whether screening followed by brief intervention would improve alcohol-related outcomes in typical medical inpatients (that is, a racially diverse group with a range of unhealthy alcohol use, comorbid conditions, and readiness to change). We hypothesized that screening and brief intervention would lead to the following: receipt of alcohol assistance (for example, specialty treatment) among persons with alcohol dependence and, among all persons decreased alcohol consumption, alcohol-related problems, and health care utilization and improved readiness to change and health-related quality of life. Methods Patients As previously described, we recruited patients from the inpatient medical service of a large, urban teaching hospital (12). Trained research associates approached all patients who were age 18 years or older and whose physicians did not decline patient contact. Patients fluent in English or Spanish who gave verbal consent were asked to complete a screening interview to determine eligibility: currently (past month) drinking risky amounts (defined for eligibility as >14 standard drinks/wk or 5 drinks/occasion for men and >11 drinks/wk or 4 drinks/occasion for women and persons 66 years); 2 contacts to assist with follow-up; no plans to move from the area in the next year; and a Mini-Mental State Examination score of 21 or greater (13, 14). Research associates assessed demographic characteristics and administered the Alcohol Use Disorders Identification Test (AUDIT) (15) by interview. To better characterize current alcohol use, they assessed the average numbers of drinking-days per week and drinks consumed on a typical day, and the maximum number of drinks consumed per occasion (16, 17). For the first 7 months of the study, research associates asked these additional questions only to patients with an AUDIT score of 8 or greater (a recommended cutoff for screening) (18). For the remaining 22 months, research associates asked the additional questions to anyone who drank in the past 12 months to maximize identification of drinkers of risky amounts. Lastly, the research associates asked all patients who were drinking risky amounts to describe their readiness to change by using a visual analog scale ranging from 0 to 10 (19). Enrolled patients provided written informed consent and were compensated for each completed interview. The institutional review board at Boston University Medical Center approved this study. We secured additional privacy protection with a certificate of confidentiality from the National Institute on Alcohol Abuse and Alcoholism. Assessment at Enrollment Research associates interviewed patients before randomization to assess the characteristics shown in Table 1. One author reviewed the medical records to determine medical diagnoses (29). Diagnoses of alcohol use disorders were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (30), and were determined with the Composite International Diagnostic Interview (CIDI) Alcohol Module (31, 32). Table 1. Characteristics at Enrollment of All Study Patients and of the Subgroup with Alcohol Dependence* Randomization and Intervention An off-site data management group generated assignments to control and intervention groups by using a permuted block (size 8) randomization procedure stratified by AUDIT score (<12 vs. 12) and provided us the assignments in sealed opaque envelopes. We used the AUDIT score to stratify because we could not score the CIDI before randomization. After each baseline assessment, research associates opened an envelope and informed the patient of his or her assignment. Patients in the control group received usual care (that is, they were told the screening results and that they could discuss their drinking with their physicians). Specialists were available by referral. Systematic alcohol screening and brief intervention were not routine at this hospital. We assigned patients in the intervention group to a 30-minute session of brief motivational counseling (19, 33) conducted by counseling and clinical psychology doctoral students whom we trained and supervised. Sessions were audiotaped and included feedback, an open discussion, and construction of a change plan (Appendix). Outcomes and Measurements The first primary outcome was self-reported receipt of alcohol assistance in the past 3 months by patients with CIDI-determined alcohol dependence. This outcome was measured at the 3-month follow-up visit with a standardized interview based on the Treatment Services Review (34) and Form 90 (35). Assistance included residential treatment, outpatient treatment (for example, specialty counseling or therapy), medications, employee assistance programs, or mutual-help groups (for example, Alcoholics Anonymous). The other primary outcome was the change in the number of mean drinks per day in the past 30 days from enrollment to 12 months among all patients. We determined consumption with the Timeline Follow-back method (36). Five secondary consumption outcomes (past 30 days) included changes from enrollment to 12 months in the numbers of heavy drinking episodes (5 drinks/occasion for men and 4 drinks/occasion for women and for persons 66 y) and days abstinent; and the proportions of patients drinking risky amounts (>14 drinks/wk or 5 drinks/occasion for men and >7 drinks/wk or 4 drinks/occasion for women and persons 66 y) (37), having 1 or more heavy drinking episodes, and abstaining for all 30 days. Other secondary outcomes included the changes at 12 months in readiness to change (Taking Steps scale on the Stages of Change Readiness and Treatment Eagerness Scale) (38), alcohol problems (total score on the Short Inventory of Problems) (39), physical and mental health-related quality of life (Physical and Mental Component Summary scale scores on the Short-Form Health Survey) (40), and emergency department visits and days of medical hospitalization (both determined by a standardized interview based on the Treatment Services Review and Form 90) (34, 35). Follow-up Procedures Research associates conducted follow-up visits, which included reassessment of most domains covered at enrollment, usually in person and at 3 and 12 months (10% and 13%, respectively, by telephone; similar by randomized group). They performed alcohol breath tests at in-person follow-up visits (41). Although they were involved in the randomization assignment, research associates were not involved in the intervention. Further, 64% of patients at 3-month follow-up and 85% of patients at 12-month follow-up were interviewed by a different research associate than at baseline. Statistical Analysis We analyzed all patients in the groups to which they were randomly assigned. Reported P values are 2-tailed and are considered statistically significant if they were less than 0.05. We analyzed data with SAS/STAT software, versions 8.2 and 9.1.3 (SAS Institute, Inc., Cary, North Carolina). To describe the study sample and to compare groups, we used the chi-square test, Fisher exact test, 2-sample t test, and Wilcoxon rank-sum test, as appropriate. For the primary analyses, we used logistic and linear

Alcohol Consumption and HIV Disease Progression: Are They Related?

BACKGROUND The relationship between alcohol consumption and HIV disease progression has received limited attention in the era of highly active antiretroviral therapy (HAART). METHODS We assessed CD4 cell count, HIV RNA levels, and alcohol consumption in the past month, defined as none, moderate, and at risk, in 349 HIV-infected people with a history of alcohol problems. We investigated the relationship between alcohol consumption and HIV disease markers CD4 cell count and HIV RNA level, stratified by HAART use, using multivariable regression. RESULTS No significant differences in CD4 cell count or HIV RNA level were found across the categories of alcohol consumption for patients who were not receiving HAART. However, among patients who were receiving HAART, log HIV RNA levels were significantly higher in those with moderate (2.17 copies/ml) and at-risk (2.73 copies/ml) alcohol use compared with none (1.73 copies/ml; p = 0.006). CD4 cell counts in those with moderate (368 cells/microl) and at-risk (360 cells/microl) alcohol use were lower than for subjects who reported none (426 cells/microl; p = 0.07). CONCLUSION Among patients who have a history of alcohol problems and are receiving antiretroviral treatment, alcohol consumption was associated with higher HIV RNA levels and lower CD4 counts. No comparable association was found for similar patients who were not receiving HAART. Addressing alcohol use in HIV-infected patients, especially those who are receiving HAART, may have a substantial impact on HIV disease progression.

Alcohol and HIV Disease Progression: Weighing the Evidence

Heavy alcohol use is commonplace among HIV-infected individuals; however, the extent that alcohol use adversely impacts HIV disease progression has not been fully elucidated. Fairly strong evidence suggests that heavy alcohol consumption results in behavioral and biological processes that likely increase HIV disease progression, and experimental evidence of the biological effect of heavy alcohol on simian immunodeficiency virus in macaques is quite suggestive. However, several observational studies of the effect of heavy alcohol consumption on HIV progression conducted in the 1990s found no association of heavy alcohol consumption with time to AIDS diagnosis, while some more recent studies showed associations of heavy alcohol consumption with declines of CD4 cell counts and nonsuppression of HIV viral load. We discuss several plausible biological and behavioral mechanisms by which alcohol may cause HIV disease progression, evidence from prospective observational human studies, and suggest future research to further illuminate this important issue.

Health literacy, antiretroviral adherence, and HIV-RNA suppression: a longitudinal perspective.

BACKGROUND: Low health literacy has been associated with worse adherence to antiretroviral therapy (ART) and higher HIV-RNA levels, but these relationships have not been evaluated in longitudinal analyses. METHODS: We evaluated literacy using the Rapid Estimate of Adult Literacy in Medicine (REALM) (≤6th grade, 7th to 8th grade, ≥9th grade) in the HIV-Alcohol Longitudinal Cohort study of HIV-infected persons with a history of alcohol problems, conducted from 1997 to 2001. We tested HIV-RNA levels and administered a standardized questionnaire regarding demographics, substance use, receipt of ART, and adherence with ART, every 6 months for up to 7 occasions. Among the 235 subjects on ART, we investigated the relationship between literacy and 2 outcomes: 100% 3-day self-reported adherence and HIV-RNA suppression (<500 copies). RESULTS: Subjects’ literacy levels were the following: 14% ≤6th grade, 29% 7th to 8th grade, and 57% ≥9th grade. In 66% of the observations (478/725), subjects reported 100% 3-day adherence with ART. Of the 685 HIV-RNA assays from these subjects, 62% had <500 copies. In unadjusted analyses, subjects with the lowest literacy level (≤6th grade) had a higher odds of adherence (odds ratio [OR] 2.23, 95% confidence interval 1.15 to 4.30) and HIV-RNA suppression (OR 2.01, 95% confidence interval 1.03 to 3.90) compared with those with ≥9th grade literacy. This trend persisted but was no longer statistically significant in adjusted models of adherence (AOR 1.93, 95% confidence interval 0.86 to 4.31) and HIV-RNA suppression (AOR 1.70, 95% confidence interval 0.79 to 3.65). CONCLUSION: Contrary to our hypothesis, low literacy was not associated with a lower odds of adherence or virologic suppression in this longitudinal analysis of HIV-infected patients with a history of alcohol problems. Indeed, trends in these data suggest the possibility that low literacy may be associated with a higher odds of adherence and virologic suppression. These counterintuitive findings underscore the need to pursue a fuller understanding of the mechanisms by which literacy affects health outcomes.