Life Chaos is Associated with Reduced HIV Testing, Engagement in Care, and ART Adherence Among Cisgender Men and Transgender Women upon Entry into Jail.

Life chaos, the perceived inability to plan for and anticipate the future, may be a barrier to the HIV care continuum for people living with HIV who experience incarceration. Between December 2012 and June 2015, we interviewed 356 adult cisgender men and transgender women living with HIV in Los Angeles County Jail. We assessed life chaos using the Confusion, Hubbub, and Order Scale (CHAOS) and conducted regression analyses to estimate the association between life chaos and care continuum. Forty-eight percent were diagnosed with HIV while incarcerated, 14% were engaged in care 12 months prior to incarceration, mean antiretroviral adherence was 65%, and 68% were virologically suppressed. Adjusting for sociodemographics, HIV-related stigma, and social support, higher life chaos was associated with greater likelihood of diagnosis while incarcerated, lower likelihood of engagement in care, and lower adherence. There was no statistically significant association between life chaos and virologic suppression. Identifying life chaos in criminal-justice involved populations and intervening on it may improve continuum outcomes

Alterations to the Gastrointestinal Microbiome Associated with Methamphetamine Use among Young Men who have Sex with Men.

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R2 = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study.

Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans.Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS).As demonstrated by statistically-significant ibudilast × MA condition interactions (p<.05), ibudilast reduced several MA-related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, -0.21]), compared to placebo.Ibudilast appeared to reduce reward-related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy

Opportunities for the development of neuroimmune therapies in addiction.

Studies have implicated neuroinflammatory processes in the pathophysiology of various psychiatric conditions, including addictive disorders. Neuroimmune signaling represents an important and relatively poorly understood biological process in drug addiction. The objective of this review is to update the field on recent developments in neuroimmune therapies for addiction. First, we review studies of neuroinflammation in relation to alcohol and methamphetamine dependence followed by a section on neuroinflammation and accompanying neurocognitive dysfunction in HIV infection and concomitant substance abuse. Second, we provide a review of pharmacotherapies with neuroimmune properties and their potential development for the treatment of addictions. Pharmacotherapies covered in this review include ibudilast, minocycline, doxycycline, topiramate, indomethacin, rolipram, anakinra (IL-1Ra), peroxisome proliferator-activated receptor agonists, naltrexone, and naloxone. Lastly, summary and future directions are provided with recommendations for how to efficiently translate preclinical findings into clinical studies that can ultimately lead to novel and more effective pharmacotherapies for addiction

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study.

Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans.Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS).As demonstrated by statistically-significant ibudilast × MA condition interactions (p<.05), ibudilast reduced several MA-related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, -0.21]), compared to placebo.Ibudilast appeared to reduce reward-related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy

Intersecting burdens: Homophobic victimization, unstable housing, and methamphetamine use in a cohort of men of color who have sex with men.

BackgroundMen who have sex with men with histories of homophobic victimization bear heightened risk of unstable housing and methamphetamine use. However, it is unclear whether unstable housing explains the link between homophobic victimization and methamphetamine use in this group. The present study aims to test associations between homophobic victimization, unstable housing, and recent methamphetamine use across 24 months in a cohort of men of color who have sex with men (MoCSM).MethodsOur analysis stems from data of 1342 person-visits from 401 MoCSM participating in an ongoing cohort study. We performed a lagged multilevel negative binominal regression to test the association between past homophobic victimization and recent unstable housing, and a lagged multilevel ordered logistic regression to test the association between past homophobic victimization recent methamphetamine use. We then performed a path analysis to test whether recent unstable housing mediates the association between past homophobic victimization and recent methamphetamine use.ResultsFindings showed homophobic victimization associated significantly with increased odds of unstable housing (IRR = 1.70, 95% CI [1.35, 2.14], p < 0.001) and recent methamphetamine use (OR = 1.40, 95% CI [1.15, 1.71], p = 0.001). Mediation analysis indicated that past homophobic victimization was indirectly associated with recent methamphetamine use via unstable housing (OR = 1.06 (95% CI [1.01, 1.11], p = 0.010).ConclusionOur findings suggest that homophobic victimization and unstable housing should be addressed alongside treatment and prevention of methamphetamine use in MoCSM

Disclosure of HIV Status and HIV Sexual Transmission Behaviors among HIV-Positive Black Men Who Have Sex with Men in the BROTHERS (HPTN 061) Study

We assessed whether disclosure of HIV status is significantly associated with reported HIV sexual risk behaviors among HIV positive Black/African American men who have sex with men (MSM) (Black MSM) in six cities in the USA. Participants from the BROTHERS (HIV Prevention Trials Network [HPTN 061]) study focused on assessing the feasibility and acceptability of a multifaceted HIV prevention intervention to reduce HIV infections among Black MSM enrolled between July 2009 and October 2010. All participants completed a behavioral assessment using an audio computer-assisted self-interview that included questions about HIV status disclosure, HIV sexual risk behaviors, and other behaviors. Biological samples were also collected. This analysis focused on baseline data of HIV-positive Black MSM in the HPTN 061 study. Of the 143 HIV-positive Black MSM (majority ≥ 35 years of age) included in this analysis, 58% reported disclosing their HIV status to their last male anal sex partner. Forty-three percent and 42% reported condomless insertive and receptive anal intercourse respectively with their last male partner; whereas, 17% and 18% of the sample engaged in condomless insertive and receptive anal intercourse with a serodiscordant/unknown status partner, respectively. In multivariable logistic regression models, there was no statistically significant association between HIV status disclosure and condomless insertive anal intercourse (aOR = 0.35, 95% CI 0.11, 1.08; p = 0.30), condomless receptive anal intercourse (aOR = 2.48, 95% CI 0.94, 6.52; p = 0.20), or condomless receptive anal intercourse with a serodiscordant/unknown status partner (aOR = 0.55, 95% CI 0.20, 1.49; p = 0.45). However, HIV status disclosure was significantly associated with lower odds of reporting condomless insertive anal intercourse with a serodiscordant/unknown status partner (aOR = 0.19, 95% CI 0.06, 0.68; p ≤ 0.01). Among this multi-city sample of HIV-positive Black MSM, disclosure of HIV status was common and associated with lower HIV sexual risk behaviors. These findings should motivate and guide research to develop prevention messages to increase HIV status disclosures

Psychiatric Illness, Substance Use, and Viral Suppression Among HIV-Positive Men of Color Who Have Sex with Men in Los Angeles.

For individuals living with human immunodeficiency virus (HIV), viral suppression positively affects quality and length of life and reduces risks for HIV transmission. Men of color who have sex with men (MoCSM) who have been diagnosed with HIV have disproportionately low rates of viral suppression, with concomitant increases in incidence. We identified specific social, structural, and psychiatric factors associated with viral suppression among a sample of 155 HIV-positive MoCSM. Cigarette smoking and biological markers of recent drug use were significantly associated with detectable viral load. In contrast, individuals reporting a history of psychiatric illness during medical examination were more likely to be virally suppressed. Further analyses demonstrated that psychiatric illness may affect virologic outcomes through increased probability of being prescribed HIV medications. Alternatively, cigarette smoking and drug use appear to negatively affect subsequent HIV Care Continuum milestones such as medication adherence. Findings provide support for comprehensive intervention programs that emphasize prevention and treatment of cigarette, methamphetamine, and other drug use, and promote improved connection to psychiatric care. Continual achievement of this goal may be a crucial step to increase rates of viral suppression and slow HIV incidence in communities of MoCSM in Los Angeles and other urban areas

Associations of Emotional, Physical, or Sexual Intimate Partner Violence and Depression Symptoms Among South African Women in a Prospective Cohort Study

Violence against women remains a significant public health problem globally. The majority of longitudinal studies documenting the negative impact of intimate partner violence (IPV) on the mental health of women come from high-income countries. The aim of this study was to investigate the longitudinal association between emotional, physical, or sexual IPV and depression symptoms among South African women in a prospective cohort study. Participants were 981 South African women enrolled in the Drakenstein Child Health Study-a cohort study investigating the early life determinants of child health. Interview data from four time-points (antenatal care visit, 6 months, 12 months, and 18 months postpartum) were included. The primary independent variable was self-reported emotional, physical, and sexual IPV in the past 12 months. Depressive symptoms were assessed at each time-point with the Edinburgh Postnatal Depression Scale (EPDS); a cutoff score of ⩾13 was used to define significant depression symptoms. We used pooled-multivariable logistic regression models to determine associations between the three different forms of IPV and significant depression symptoms while adjusting for time-fixed and time-updated covariates. The mean age of the sample at antenatal care visit was 27 years (standard deviation = 6.0). In the adjusted model including all forms of IPV and adjusting for sociodemographic and clinical characteristics, substance use, and childhood trauma, emotional (adjusted odds ratio [aOR] =1.55, 95% confidence interval (CI): [1.02, 2.34]; p = .039)] and sexual (aOR = 2.02, 95% CI: [1.10, 3.72]; p < .001) IPV were significantly associated with significant depression symptoms. The relationship between physical IPV and significant depression symptoms was not statistically significant (aOR = 0.68, 95% CI: [0.44, 1.05]; p = .485). Our study confirms findings from high-income countries of the association between IPV and depressive symptoms among women in South Africa. Routine screening for IPV, including emotional IPV and intervention programs for IPV among women, is needed in South Africa