Starley B. Shade

Cannabis in painful HIV-associated sensory neuropathy A randomized placebo-controlled trial

Objective: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. Methods: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model. Results: Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = −71, −16) vs 17% (IQR = −29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p ≤ 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported. Conclusion: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy

Objective: To determine the extent to which HIV-infected patients, including those with advanced immunodeficiency, can reverse peripheral CD4 T-cell depletion while maintaining long-term viral suppression on highly active antiretroviral therapy. Design: Cohort study. Participants: Four-hundred and twenty-three HIV-infected patients who initiated HAART prior to 1998 and achieved a viral load ⩽ 1000 copies/ml by 48 weeks were evaluated for up to 4 years or until plasma HIV RNA levels increased to > 1000 copies/ml. Main outcome measure: CD4 count changes. Results: Among patients who maintained plasma HIV RNA levels ⩽ 1000 copies/ml, CD4 counts continued to increase through year 4 of HAART. In the last year examined, from year 3 to 4 of HAART, mean CD4 count gains were +89 × 106, +86 × 106, +95 × 106, and +88 × 106/l in patients with pre-therapy CD4 counts of < 50 × 106, 50 × 106–199 × 106, 200 × 106–349 × 106, and ⩾ 350 × 106/l, respectively (all gains were significantly greater than zero; P < 0.05). Among those with a pre-therapy CD4 count of < 50 × 106/l, 88% achieved a CD4 cell count of ⩾ 200 × 106/l and 59% achieved a count of ⩾ 350 × 106/l by year 4. Factors associated with increased CD4 cell count gains from month 3 to year 4 included lower pre-therapy CD4 cell count, younger age, female sex, and infrequent low-level viremia (versus sustained undetectable viremia). Conclusions: Most patients who achieve and maintain viral suppression on HAART continue to experience CD4 T-cell gains through 4 years of therapy. The immune systems capacity for CD4 T lymphocyte restoration is not limited by low pre-therapy CD4 counts.

Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study.

Abstract Objective: To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. Design: Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. Setting: Eastern Finland. Subjects: 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. Main outcome measures: Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. Results: Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P<0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138v 0.123 mm) and maximum (0.320 v 0.261 mm) intima-media thickness and plaque height (0.347 v 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. Conclusions: Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis. Key messages Psychological stress plays an important part in the illness and premature death associated with cardiovascular disease, but individual susceptibility to disease varies according to biological predispositions, personality, behaviour, and environmental exposures This study found that a demanding work environment in combination with a predisposition to exaggerated blood pressure reactivity to stress was significantly related to progression of carotid atherosclerosis over four years among employed middle aged men and was independent of known atherosclerotic risk factors These findings support the role of stress induced reactivity in human atherogenesis Future research needs to confirm these findings in other populations and to examine the influence of other risk factors and environments on the progression of disease

Suicidal behavior and sexual/physical abuse among street youth

OBJECTIVE To examine the relationship between home life risk factors and suicide attempts among homeless and runaway street youth recruited from both shelters and street locations in Denver, CO; New York City; and San Francisco, CA. METHOD Street youth 12-19 years old (N = 775) were recruited by street outreach staff in Denver, New York City and San Francisco in 1992 and 1993 and interviewed. Cross-sectional, retrospective data were analyzed to examine the relationship between suicide attempts and antecedent home life variables. Logistic regression was used to identify factors predicting suicide attempts. RESULTS Forty-eight percent of the females and 27% of the males had attempted suicide. The mean number of suicide attempts was 6.2 (SD = 12.9) for females and 5.1 for males (SD = 7.6). Among females, 70% reported sexual abuse and 35% reported physical abuse. Among males, 24% reported sexual abuse and 35% reported physical abuse. Sexual and physical abuse before leaving home were independent predictors of suicide attempts for females and males. Other home life factors hypothesized to be risk factors for suicide attempts were not significant. Interaction terms were not significant. Among street youth who were sexually or physically abused in this sample, the odds of attempting suicide were 1.9 to 4.3 times the odds of attempting suicide among those not sexually or physically abused. CONCLUSIONS Interventions attempting to reduce risky behaviors in this population must include assessments of suicidal behaviors as well as components for assisting youth in dealing with the behavioral and emotional sequelae of physical and sexual abuse.

Vaporization as a smokeless cannabis delivery system: a pilot study.

Although cannabis may have potential therapeutic value, inhalation of a combustion product is an undesirable delivery system. The aim of the study was to investigate vaporization using the Volcano® device as an alternative means of delivery of inhaled Cannabis sativa. Eighteen healthy inpatient subjects enrolled to compare the delivery of cannabinoids by vaporization to marijuana smoked in a standard cigarette. One strength (1.7, 3.4, or 6.8% tetrahydrocannabinol (THC)) and delivery system was randomly assigned for each of the 6 study days. Plasma concentrations of Δ‐9‐THC, expired carbon monoxide (CO), physiologic and neuropsychologic effects were the main outcome measures. Peak plasma concentrations and 6‐h area under the plasma concentration–time curve of THC were similar. CO levels were reduced with vaporization. No adverse events occurred. Vaporization of cannabis is a safe and effective mode of delivery of THC. Further trials of clinical effectiveness of cannabis could utilize vaporization as a smokeless delivery system.

Cannabinoid-Opioid Interaction in Chronic Pain

Cannabinoids and opioids share several pharmacologic properties and may act synergistically. The potential pharmacokinetics and the safety of the combination in humans are unknown. We therefore undertook a study to answer these questions. Twenty–one individuals with chronic pain, on a regimen of twice–daily doses of sustained–release morphine or oxycodone were enrolled in the study and admitted for a 5–day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2–4, and in the morning of day 5. Blood sampling was performed at 12–h intervals on days 1 and 5. The extent of chronic pain was also assessed daily. Pharmacokinetic investigations revealed no significant change in the area under the plasma concentration–time curves for either morphine or oxycodone after exposure to cannabis. Pain was significantly decreased (average 27%, 95% confidence interval (CI) 9, 46) after the addition of vaporized cannabis. We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels. The combination may allow for opioid treatment at lower doses with fewer side effects.

Individual, Interpersonal, and Structural Correlates of Effective Haart Use Among Urban Active Injection Drug Users

Summary: Among individuals receiving highly active antiretroviral therapy (HAART), injection drug users (IDUs) are less likely to achieve HIV suppression. The present study examined individual-level, interpersonal, and structural factors associated with achieving undetectable plasma viral load (UVL) among US IDUs receiving recommended HAART. Data were from baseline assessments of the INSPIRE (Interventions for Seropositive Injectors-Research and Evaluation) study, a 4-site, secondary HIV prevention intervention for heterosexually active IDUs. Of 1113 study participants at baseline, 42% (n = 466) were currently taking recommended HAART (34% were female, 69% non-Hispanic black, 26% recently homeless; median age was 43 years), of whom 132 (28%) had a UVL. Logistic regression revealed that among those on recommended HAART, adjusted odds of UVL were at least 3 times higher among those with high social support, stable housing, and CD4 > 200; UVL was approximately 60% higher among those reporting better patient-provider communication. Outpatient drug treatment and non-Hispanic black race and an interaction between current drug use and social support were marginally negatively significant. Among those with high perceived support, noncurrent drug users compared with current drug users had a greater likelihood of UVL; current drug use was not associated with UVL among those with low support. Depressive symptoms (Brief Symptom Inventory) were not significant. Results suggest the major role of social support in facilitating effective HAART use in this population and suggest that active drug use may interfere with HAART use by adversely affecting social support. Interventions promoting social support functioning, patient-provider communication, stable housing, and drug abuse treatment may facilitate effective HAART use in this vulnerable population.

Family model of HIV care and treatment: a retrospective study in Kenya

BackgroundNyanza Province, Kenya, had the highest HIV prevalence in the country at 14.9% in 2007, more than twice the national HIV prevalence of 7.1%. Only 16% of HIV-infected adults in the country accurately knew their HIV status. Targeted strategies to reach and test individuals are urgently needed to curb the HIV epidemic. The family unit is one important portal.MethodsA family model of care was designed to build on the strengths of Kenyan families. Providers use a family information table (FIT) to guide index patients through the steps of identifying family members at HIV risk, address disclosure, facilitate family testing, and work to enrol HIV-positive members and to prevent new infections. Comprehensive family-centred clinical services are built around these steps. To assess the approach, a retrospective study of patients receiving HIV care between September 2007 and September 2009 at Lumumba Health Centre in Kisumu was conducted. A random sample of FITs was examined to assess family reach.ResultsThrough the family model of care, for each index patient, approximately 2.5 family members at risk were identified and 1.6 family members were tested. The approach was instrumental in reaching children; 61% of family members identified and tested were children. The approach also led to identifying and enrolling a high proportion of HIV- positive partners among those tested: 71% and 89%, respectively.ConclusionsThe family model of care is a feasible approach to broaden HIV case detection and service reach. The approach can be adapted for the local context and should continue to utilize index patient linkages, FIT adaption, and innovative methods to package services for families in a manner that builds on family support and enhances patient care and prevention efforts. Further efforts are needed to increase family member engagement.

Sexual risk factors among self-identified lesbians, bisexual women, and heterosexual women accessing primary care settings.

Objectives: There is scant data on the sexual behaviors of women of diverse sexual orientations in a low-risk population. Goals: The goals of this study were to sample women of all sexual orientations in primary care settings and to evaluate sexual behaviors and risk for HIV and other sexually transmitted diseases (STDs). Study: A total of 1,304 women (self-identified as 49% heterosexual, 11% bisexual, and 40% lesbian) were surveyed by anonymous questionnaire at 33 healthcare sites. Results: Among women who recently had sex with men (N = 600), 51% reported ever using condoms. Heterosexual women were at highest risk for acquiring HIV as a result of lack of condom use (P <0.001), particularly in higher-risk situations. Bisexual women reported substance use with sex at a higher rate than lesbians or heterosexual women (P <0.001). Lesbians had higher rates of sex with bisexual men (P <0.001) and injection drug users (P <0.02), but also a higher rate of condom use (P <0.001) compared with bisexual or heterosexual women. Conclusion: Women of all sexual orientations, and particularly heterosexual women, engaged in behaviors that put them at risk for HIV and STD.

The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir.

Background and objectives The use of cannabinoids for appetite stimulation and the management of wasting and antiretroviral side-effects has become a common practice in the care of HIV-infected individuals. We present pharmacokinetic data from a randomized placebo-controlled study designed to evaluate the metabolic effects of smoked marijuana and dronabinol in HIV-infected patients receiving indinavir (IDV) or nelfinavir (NFV). Methods Subjects on stable regimens containing IDV 800 mg every 8 h (n = 28) or NFV 750 mg three time a day (n = 34) were randomized to one of three treatment arms: 3.95% THC marijuana cigarettes, dronabinol 2.5 mg capsules or placebo capsules administered three times daily. Serial blood sampling was performed at baseline and on day 14 of treatment. The changes in NFV and IDV pharmacokinetics were measured as the median percentage change from baseline. Results At day 14, the 8-h area under the curve (AUC8) changed by −10.2% (P = 0.15), maximum concentration (Cmax) by −17.4% (P = 0.46), and minimum concentration (Cmin) by −12.2% (P = 0.28) for patients in the NFV marijuana arm (n = 11). Similar decreases had occurred by day 14 among patients in the IDV marijuana arm (n = 9): AUC8 had changed by −14.5% (P = 0.074), Cmax by −14.1% (P = 0.039), and Cmin by −33.7% (P = 0.65). Conclusion Despite a statistically significant decrease in Cmax of IDV in the marijuana arm, the magnitude of changes in IDV and NFV pharmacokinetic parameters in the marijuana arm are likely to have no short-term clinical consequence. The use of marijuana or dronabinol is unlikely to impact antiretroviral efficacy.