Alcohol and drug use severity are independently associated with antiretroviral adherence in the current treatment era.

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.

Effect of alcohol consumption on all-cause and liver-related mortality among HIV-infected individuals.

OBJECTIVES: The aim of the study was to examine the association between levels of past and current alcohol consumption and all-cause and liver-related mortality among people living with HIV (PLWH). METHODS: A prospective cohort study of 1855 PLWH in Baltimore, MD was carried out from 2000 to 2013. We ascertained alcohol use by (1) self-report (SR) through a computer-assisted self interview, and (2) medical record abstraction of provider-documented (PD) alcohol use. SR alcohol consumption was categorized as heavy (men: > 4 drinks/day or > 14 drinks/week; women: > 3 drinks/day or > 7 drinks/week), moderate (any alcohol consumption less than heavy), and none. We calculated the cumulative incidence of liver-related mortality and fitted adjusted cause-specific regression models to account for competing risks. RESULTS: All-cause and liver-related mortality rates (MRs) were 43.0 and 7.2 per 1000 person-years (PY), respectively. All-cause mortality was highest among SR nondrinkers with PD recent (< 6 months) heavy drinking (MR = 85.4 deaths/1000 PY) and lowest among SR moderate drinkers with no PD history of heavy drinking (MR = 23.0 deaths/1000 PY). Compared with SR moderate drinkers with no PD history of heavy drinking, SR nondrinkers and moderate drinkers with PD recent heavy drinking had higher liver-related mortality [hazard ratio (HR) = 7.28 and 3.52, respectively]. However, SR nondrinkers and moderate drinkers with a PD drinking history of > 6 months ago showed similar rates of liver-related mortality (HR = 1.06 and 2.00, respectively). CONCLUSIONS: Any heavy alcohol consumption was associated with all-cause mortality among HIV-infected individuals, while only recent heavy consumption was associated with liver-related mortality. Because mortality risk among nondrinkers varies substantially by drinking history, current consumption alone is insufficient to assess risk.

A Comparison of Adherence Timeframes Using Missed Dose Items and Their Associations with Viral Load in Routine Clinical Care: Is Longer Better?

Questions remain regarding optimal timeframes for asking about adherence in clinical care. We compared 4-, 7-, 14-, 30-, and 60-day timeframe missed dose items with viral load levels among 1099 patients on antiretroviral therapy in routine care. We conducted logistic and linear regression analyses examining associations between different timeframes and viral load using Bayesian model averaging (BMA). We conducted sensitivity analyses with subgroups at increased risk for suboptimal adherence (e.g. patients with depression, substance use). The 14-day timeframe had the largest mean difference in adherence levels among those with detectable and undetectable viral loads. BMA estimates suggested the 14-day timeframe was strongest overall and for most subgroups although findings differed somewhat for hazardous alcohol users and those with current depression. Adherence measured by all missed dose timeframes correlated with viral load. Adherence calculated from intermediate timeframes (e.g. 14-day) appeared best able to capture adherence behavior as measured by viral load.

Differential expression of guanosine triphosphate binding proteins in men at high and low risk for the future development of alcoholism.

We evaluated G-proteins that are components of adenylyl cyclase (AC) signal transduction in erythrocyte and lymphocyte membranes from 26 family history positive (FHP) non-alcoholic and 26 family history negative (FHN) nonalcoholic subjects. Subjects were classified as FHP if their father met criteria for alcohol dependence; as FHN, if there was no history of alcoholism in any first or second degree relatives. Immunoblot analysis indicated that levels of erythrocyte membrane Gs alpha from FHP subjects were greater than levels in FHN subjects (171 +/- 11 vs 100 +/- 6, P < 0.001). To confirm the results of the immunoblot analysis, Gs alpha was quantitated by cholera toxin-dependent [32P]ADP-ribosylation. Levels of erythrocyte [32P]ADP-ribose-Gs alpha from FHP subjects were greater than levels in FHN subjects (236 +/- 28 vs 100 +/- 14, P < 0.001). Gs alpha levels did not correlate with age or alcohol consumption. By contrast to differences in Gs alpha, immunoblot analysis showed similar levels of Gi(2)alpha and Gi(3)alpha in erythrocyte membranes of FHP and FHN subjects. Pertussis toxin-catalyzed [32P]ADP-ribosylation of Gi-like G-proteins confirmed the immunoblot observations. Lastly, compared to FHN subjects, FHP subjects had enhanced Gs alpha expression in lymphocyte membranes as well (138 +/- 11 vs 100 +/- 5.5; P < 0.02). In summary, compared to FHN nonalcoholic men, FHP nonalcoholic men had greater levels of the stimulatory G-protein, Gs alpha, in erythrocyte and lymphocyte membranes. Enhanced expression of Gs alpha may be a marker of increased risk for the future development of alcoholism.

Alcohol and drug use disorders, HIV status and drug resistance in a sample of Russian TB patients.

SETTING: Alcohol use, tuberculosis (TB) drug resistance and human immunodeficiency virus (HIV) risk behavior are of increasing concern in Russian TB patients. DESIGN: A prevalence study of alcohol use and HIV risk behavior was conducted in a sample of 200 adult men and women admitted to TB hospitals in St Petersburg and Ivanovo, Russia. RESULTS: Of the subjects, 72% were men. The mean age was 41. Active TB was diagnosed using a combination of chest X-ray, sputum smears and sputum cultures. Sixty-two per cent met DSM-IV criteria for current alcohol abuse or dependence. Drug use was uncommon, with only two patients reporting recent intravenous heroin use. There was one case of HIV infection. The mean total risk assessment battery score was 3.4. Depression was present in 60% of the sample, with 17% severely depressed. Alcohol abuse/dependence was associated with an eight-fold increase in drug resistance (OR 8.58; 95% CI 2.09-35.32). Patients with relapsing or chronic TB were more likely to meet the criteria for alcohol abuse/dependence (OR 2.56; 95% CI 1.0-6.54). CONCLUSION: Alcohol use disorders are common in patients being treated for active TB, and are associated with significant morbidity. Additional surveys are needed to examine the relationship between alcohol use disorders and anti-tuberculosis drug resistance.

Family history of alcoholism and hypothalamic opioidergic activity.

BACKGROUND: This study was designed to assess whether nonalcoholic offspring from families with a high density of alcohol-dependent individuals have altered endogenous central nervous system opioid activity. Naloxone hydrochloride stimulates plasma cortisol by blocking opioidergic input on the corticotropin-releasing factor neuron, thereby providing a noninvasive method for measuring hypothalamic opioid tone. METHODS: Forty-eight nonalcoholic subjects aged 18 to 25 years were enrolled in a protocol to measure endogenous opioid activity by inducing opioid receptor blockade with the receptor antagonist, naloxone. Twenty-six subjects were offspring from families with a high density of alcohol dependence and were designated as family history-positive subjects. Twenty-two subjects were biological offspring of nonalcohol-dependent parents and designated as family history-negative subjects. Subjects received naloxone hydrochloride (0, 125, and 375 microg/kg) in double-blind, randomized order. Serum cortisol levels were monitored. RESULTS: Family history-negative subjects had a graded cortisol response to each dose of naloxone. In contrast, family history-positive subjects achieved a maximal cortisol response to the 125-microg/kg dose of naloxone hydrochloride with no further increase in cortisol levels observed following the 375-microg/kg dose. Family history-negative subjects had a diminished cortisol response to the 125-microg/kg dose compared with the family history-positive subjects. Plasma naloxone concentrations did not differ between family history groups. CONCLUSIONS: Individuals from families with a high density of alcohol dependence are more sensitive to naloxone compared with offspring of nonalcohol-dependent parents. This implies that individuals with a family history of alcohol dependence have diminished endogenous hypothalamic opioid activity.

Plasma adrenocorticotropin responses to opioid blockade with naloxone: generating a dose-response curve in a single session.

We examined two methods of generating a dose-response curve to the opioid receptor antagonist naloxone. In 15 healthy male subjects (18-25 years) plasma adrenocorticotropin (ACTH) responses to five doses of naloxone studied over 5 separate days were compared to plasma ACTH responses to five incremental doses of naloxone studied within a single session. There was a statistically significant positive correlation in ACTH responses (area under the curve and peak) between dosing methods. Furthermore, the doses of naloxone that produced half-maximal and maximal ACTH response were similar. The comparability of ACTH responses between the two naloxone dosing techniques, combined with the safety and ease associated with the single-session methodology, underscores the usefulness of the single-session technique for future investigations.

Short-term effects of oral methadone in methadone maintenance subjects.

In two experiments the physiologic and subjective status of methadone maintenance patients was assessed during the presumed peak (0 to 6 hr postmethadone) and during the presumed nadir of the daily methadone effect (18 to 30 hr postmethadone). In the first experiment physiologic and subjective responses were measured in seven ambulatory subjects at 2, 4, and 6 hr after a regular daily dose of methadone or placebo. In the second, physiologic measures were continuously monitored for 4 hr in six inactive seated subjects. In both studies, pupil diameter decreased after moderate to high methadone doses (35 to 80 mg). In the second experiment, heart rate fell and skin temperature rose significantly after methadone. Responses to the morphine-benzedrine group scale of the Addiction Research Center Inventory were elevated after methadone for most subjects in both studies, although there were individual differences in the magnitude and time course of this effect. Finally, low methadone maintenance doses of 10 and 20 mg/day had little or no effect on physiologic or subjective responses in two subjects. These studies showed that short-term effects of oral methadone can be readily detected during a 24-hr dosing regimen. The changes in function after the regular maintenance dose may result both from short-term opiate effects and relief of mild withdrawal.

Pupillary response to methadone challenge in heroin users.

The relationship between self-reported illicit heroin use and pupillary response to a low-dose methadone challenge was examined in 28 men beginning methadone therapy for opiate dependence. Pupil diameter was assessed before and 60, 90, and 120 minutes after a 20 mg methadone dose on day 1 of treatment. Self-reports of opiate drug effects were also taken at these times. There was a significant negative correlation (r = -0.53) between pupillary constriction 120 minutes after drug dosing and the average dollar value of subjects' reported heroin use per week. In other words, those who showed the least pupillary constriction generally reported the highest amount of illicit heroin use. Total years since first opiate use was also a significant predictor of pupillary response (r = -0.46). Self-reported amount of heroin use and years since first opiate use together accounted for 60% of the total variance in pupillary response to the challenge (Mult r = 0.77). Pupillary response to a low-dose methadone challenge appears to be a clinically practical and objective method for determining opiate tolerance levels in applicants for methadone therapy.

Oral methadone self-administration: effects of dose and alternative reinforcers.

We examined the efficacy of oral methadone as a reinforcer by offering methadone maintenance patients the chance to self-administer extra doses of methadone occasionally in addition to their regular dose. Seven maintenance patients received twice-weekly choices between methadone doses or money. Doses were 0, 1, 5, 10, 25, or 50 mg methadone; the alternative money option was $1 or $5. Extra methadone doses were reliably self-administered by maintenance patients, and percent of dose choices rose as the size of the dose offered increased. Thus extra methadone doses functioned as reinforcers in this situation. Further, across the entire dose range, more dose choices were selected when $1 was offered than when $5 was offered as an alternative. Thus methadone self-administration was influenced by the alternative reinforcers available for drug refusal. Neither reports of subjective withdrawal symptoms nor reduction of symptoms after extra methadone predicted methadone self-administration, but dose selections were more likely when urinalysis results indicated recent illicit opiate use. The reinforcing effects of oral methadone in methadone-tolerant patients may be an important factor in the popularity of this treatment among drug abusers and in the long-term treatment retention generally observed during methadone maintenance.

Naltrexone dampens ethanol-induced cardiovascular and hypothalamic- pituitary-adrenal axis activation.

Alcohol ingestion activates the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. This study examined naltrexone effects on alcohol-induced increases in physiological responses and their association with alcohol liking. Using a within-subjects design, heavy drinking men (N = 19) were maintained on each of three naltrexone doses (0, 50, and 100 mg, p.o.) over an 8-day inpatient stay. Within each naltrexone dose, subjects had three alcohol challenge sessions (none, moderate, high) in random order. Autonomic, subjective and endocrine measurements were collected regularly prior to and following alcohol administration. High-dose alcohol ingestion increased heart rate, diastolic blood pressure, skin temperature, ACTH, cortisol and liking of drink effects; responses following the moderate alcohol dose were less consistent. Naltrexone significantly dampened alcohol-induced increases in heart rate, diastolic blood pressure, hormone levels and subjective liking of drink effects. This dampening of cardiovascular and hormonal responses may contribute to the therapeutic effectiveness of naltrexone for reducing alcohol liking and decreasing relapse in alcohol-dependent persons.

Naltrexone alters subjective and psychomotor responses to alcohol in heavy drinking subjects.

Preclinical studies support endogenous opioid system involvement in alcohol reinforcement and consumption; however, recent clinical trials and human laboratory studies have provided mixed findings of the effects of naltrexone (a non-selective opioid antagonist) on alcohol responses. This study used a within-subject design (n = 23) to investigate naltrexone effects (0, 50 and 100 mg qd) on subjective and psychomotor responses to alcohol (none, moderate, high) in heavy drinkers. Before alcohol administration, subjects reported decreased desire to drink alcohol when maintained on 50 mg compared with placebo naltrexone. Following alcohol administration, active naltrexone significantly increased subjective ratings of sedative, and unpleasant/sick effects and decreased ratings of liking, best effects and desire to drink. Naltrexone generally did not alter subjective or objective indicators of drunkenness. Finally, high doses of naltrexone and alcohol interacted to produce the greatest decreases in liking and best effects. Findings support the role of endogenous opioids as determinants of alcohol's effects and suggest that naltrexone may be particularly clinically useful in those treatment patients who continue to drink heavily.

Hydromorphone effects on human conversational speech.

The present study provides an objective assessment of the increased talkativeness associated with acute opiate drug administration. Speech of five methadone-maintenance subjects was recorded continuously for 1 h following the injection of 0, 10, 14, or 18 mg hydromorphone. Dose-related increases in subjects' speech were observed, while no systematic changes were seen in speech of an undrugged partner. Dose-related increases were also obtained on an adjective checklist measuring characteristic opiate signs and symptoms. The relationship between behavioral, subjective, and reinforcing drug effects is discussed.

Predictors of outpatient treatment retention: patient versus substance use characteristics.

The present study examined predictors of participation and retention for patients treated at an urban, hospital-based outpatient substance abuse treatment clinic. All patients were interviewed using the Addiction Severity Index (ASI) at the time of admission. Based on lifetime diagnostic history of psychoactive substance abuse/dependence, patients (N=268) were classified as: alcohol-only, drug(s)-only, and alcohol+drug(s). Alcohol-only patients were significantly older, more likely to be Caucasian, married, have less than a high school education, and be employed than drug-only or alcohol/drug patients. Using multiple regression analysis, substance use status did not predict treatment participation and retention, whereas race, gender and employment composite score were significant predictors. Specifically, patients attended more sessions and remained in treatment longer if they were Caucasian, male and had a high employment composite score. These findings suggest that type of substance abuse may be overemphasized as a predictor of outpatient drug-free treatment retention, and that greater emphasis should be placed on tailoring treatment to patients' cultural, gender and vocational needs.

Treatment outcome in methadone detoxification: relationship to initial levels of illicit opiate use.

Two groups each of 10 patients enrolled in a 90-day outpatient detoxification program were classified on the basis of high (92.5% of tests) and low (7.5% of tests) rates of opiate-positive urine test results during two weeks of dosage stabilization. Pretreatment demographic variables did not differ between the two groups. Relapse to opiate use during the detoxification occurred in patients who were initially opiate free. By the end of the dose reduction period, opiate-positive rates were 60% and 87% of tests for the low and high opiate use groups, respectively. Sedative use and missed clinic days showed similar trends for both groups during the detoxification, although different patterns of drop-out from treatment were noted. Symptomatology increased during dose reduction for the low- but not for the high-frequency opiate group. In general, treatment outcome appeared equally poor for patients who showed low or high levels of illicit opiate drug use early in detoxification treatment.

Prenatal care and drug use in pregnant women.

This case-control study tested the hypothesis that pregnant inner-city women with low utilization of prenatal care are likely to be frequent drug users. Cases registered consecutively for prenatal care at > or = 28 weeks gestation or had < 4 prenatal visits. Controls were matched to cases by date of delivery. 24/81 (30%) cases and 16/128 (12%) controls were frequent drug users (adjusted odds ratio = 2.5; 95% CI, 1.2-5.4). Drug use (P = 0.01) and socioeconomic status (P = 0.001) were significantly correlated with prenatal care utilization. Self-report alone failed to note as many drug users as toxicology screen alone. Both substance use history and toxicology screen are advisable in women with low utilization of prenatal care.

Chronic opiate use during methadone detoxification: effects of a dose increase treatment.

The effects of administering high methadone doses during detoxification treatment were examined on illicit opiate use and treatment retention in chronic opiate supplementors. Twenty-six applicants to a 90-day outpatient detoxification program who delivered 50% or more opiate-positive urine samples during treatment weeks 2 and 3 were randomly assigned to receive a constant 30-mg dose through treatment week 10 or an increase to 60 mg in week 4 with gradual reduction to 30 mg by week 10. Dosage for both groups was reduced to 0 mg during weeks 11-13. Treatment retention was better for experimental (median = 86 days) than for control (median = 41 days) subjects, but the difference was not statistically significant. In the dose increase group, percent opiate-positive urines decreased from 80% to 62% during the first two weeks of dose increase (t = 2.39, P less than 0.05); opiate positive rates for the control group remained above 80%. A 20% between group difference in percent of opiate positive urine tests persisted through study week 10 in subjects (N = 5 control, 7 experimental) who remained in treatment this long. Although the blind dose increase did improve treatment outcome, we concluded that the magnitude of the effect in this population of chronic opiate supplementors was insufficient to judge the procedure clinically useful.

Cost-effectiveness of treatment for drug-abusing pregnant women.

Neonatal intensive care unit (NICU) and drug treatment costs were compared in two groups of pregnant drug abusing women: 100 admissions to a multidisciplinary treatment program and active in care at the time of delivery and 46 controls not entering drug treatment. Clinical measures included urine toxicology at delivery, infant birthweight. Apgar scores and need for and duration of NICU services. Cost measures included drug treatment and NICU costs. Treatment patients showed better clinical outcome at delivery, with less drug use and higher infant estimated gestational age, birthweight and Apgar scores. Infants of treatment patients were also less likely to require NICU services and, for those that did, had a shorter stay. When total cost was examined (including drug treatment), mean net savings for treatment subjects was $4644 per mother/infant pair. The study demonstrates the cost-effectiveness of treatment for pregnant drug abusing women, with savings in NICU costs exceeding costs of drug treatment.

Familial density of alcoholism: effects on psychophysiological responses to ethanol.

Recent research findings suggest that the patterning of familial alcoholism may critically determine ethanol sensitivity and severity of alcohol-related problems in the offspring. The present study examined the effects of familial alcoholism density on psychophysiological responses to ethanol administration in college males. Subjects with a positive family history of alcoholism were classified into affected biological father only (LD-FHP) versus both father and at least one second-degree affected relative (HD-FHP), and were compared to family history negative (FHN) subjects. Subjects received 1 g/kg ethanol or placebo in a double-blind procedure. A battery of subjective, physiological and psychomotor measures were collected once prior to and four times following drink administration. HD-FHP subjects showed significantly greater subjective effects, body sway and skin conductance after alcohol ingestion than either FHN or LD-FHP subjects; in contrast, there was no difference on any measure for LD-FHP versus FHN subjects. Our findings of increased ethanol sensitivity as a function of familial density of alcoholism strongly suggest the importance of carefully defining family history characteristics in all studies examining potential markers or risk factors for alcoholism.

Contingency management interventions: effects on treatment outcome during methadone detoxification.

We examined the effectiveness of a contingency management program in preventing relapse to illicit opiate use and increasing treatment retention during outpatient methadone detoxification treatment. Twenty male opiate addicts were randomly assigned to an experimental or control group. Following a 3-week methadone stabilization period, men in both groups received identical gradual methadone dose reductions during Weeks 4 through 9 and were maintained on placebo during Weeks 10 through 13. Beginning in Week 4, control patients received $5.00 for providing a specimen twice weekly. Experimental patients received $10.00 and a take home methadone dose for each opiate-free urine specimen but forfeited the incentives and participated in more intensive clinic procedures when specimens were opiate positive. The contingency management procedure slowed the rate of relapse to illicit opiate use. Experimental patients provided significantly more opiate-free urines during the methadone dose reduction in Weeks 4 through 9 than control patients, although the difference between groups was no longer significant during placebo administration in Weeks 10 through 13. In addition, the contingency management program improved treatment retention and reduced symptom complaints during the detoxification. The usefulness and limitations of contingency management procedures for outpatient methadone detoxification are discussed.