Perceived influence of alcohol consumption, substance use, and mental health on PrEP adherence and condom use among PrEP-prescribed gay, bisexual, and other men-who-have-sex-with-men: a qualitative investigation.

BACKGROUND: Gay, bisexual, and other men-who-have-sex-with-men (GBMSM) continue to be disproportionately affected by Human Immunodeficiency Virus (HIV). Although HIV pre-exposure prophylaxis (PrEP) offers an effective means of reducing incident HIV among this population, the HIV-preventive success of oral-based PrEP is contingent upon regimen adherence. Elevated rates of alcohol-, substance use-, and mental health-related issues among GBMSM potentially hinder PrEP-taking efforts, however the evidence for this remains mixed. Accordingly, the present study entailed a comprehensive qualitative investigation to explore PrEP-prescribed GBMSM's perceptions surrounding the influence of alcohol, substance use, and mental health on PrEP adherence. METHODS: PrEP-prescribed GBMSM (age ≥ 18 years; prescribed PrEP for ≥ 3 months) were recruited from two PrEP-delivery clinics in Toronto, Canada for focus groups as part of the formative phase of an alcohol-, substance use-, and mental health-focused randomized controlled intervention trial. Focus group discussions qualitatively explored perceived strengths and barriers associated with adherence to PrEP treatment; with an emphasis on alcohol, substance use, and mental health concerns. Condom use among PrEP-prescribed GBMSM within the context of these concerns was also discussed. RESULTS: A total of five focus groups involving 35 GBMSM were conducted (4-10/group; mean age = 42.4; white = 71.4%). Although participants themselves generally reported successfully adhering to their PrEP regimens-resulting from a strong, underlying motivation for self-care-they recognized the detrimental impact that alcohol, substance use, and mental health had on adherence among their peers. In this regard, alcohol and substances were perceived as detracting from adherence only when consumption was excessive or temporally linked to PrEP dosing. Pronounced mental health issues (e.g., severe depression) were also seen as hindering adherence, although these effects were nuanced and perceived as person-dependent. Alcohol and substances were linked to condomless sex, regardless of PrEP use, and PrEP was therefore viewed as an HIV-protective 'safety net.' CONCLUSIONS: Overall, findings suggest that PrEP adherence can often be successfully achieved in the presence of alcohol-, substance use-, and mental health-related issues. Augmenting self-care, and addressing pronounced addictions- and mental health-related concerns, may enhance PrEP treatment among GBMSM.

Alcohol consumption, substance use, and depression in relation to HIV Pre-Exposure Prophylaxis (PrEP) nonadherence among gay, bisexual, and other men-who-have-sex-with-men.

BACKGROUND: Although HIV pre-exposure prophylaxis (PrEP) substantially diminishes the likelihood of HIV acquisition, poor adherence can decrease the HIV-protective benefits of PrEP. The present investigation sought to identify the extent to which alcohol consumption, substance use, and depression were linked to PrEP nonadherence among gay, bisexual, and other men-who-have-sex-with-men (gbMSM). METHODS: gbMSM (age ≥ 18, prescribed PrEP for ≥3 months) were recruited from two clinics in Toronto, Canada for an e-survey assessing demographics; PrEP nonadherence (4-day PrEP-focused ACTG assessment); hazardous and harmful alcohol use (AUDIT scores of 8-15 and 16+, respectively); moderate/high risk substance use (NIDA M-ASSIST scores > 4); depression (CESD-10 scores ≥10); and other PrEP-relevant factors. The primary outcome, PrEP nonadherence, entailed missing one or more PrEP doses over the past 4 days. A linear-by-linear test of association assessed whether increasing severity of alcohol use (i.e., based on AUDIT categories) was linked to a greater occurrence of PrEP nonadherence. Univariate logistic regression was employed to determine factors associated with PrEP nonadherence, and factors demonstrating univariate associations at the p < .10 significance level were included in a multivariate logistic regression model. Additive and interactive effects involving key significant factors were assessed through logistic regression to evaluate potential syndemic-focused associations. RESULTS: A total of 141 gbMSM (Mean age = 37.9, white = 63.1%) completed the e-survey. Hazardous/harmful drinking (31.9%), moderate/high risk substance use (43.3%), and depression (23.7%) were common; and one in five participants (19.9%) reported PrEP nonadherence. Increasing alcohol use level was significantly associated with a greater likelihood of nonadherence (i.e., 15.6, 25.0, and 44.4% of low-risk, hazardous, and harmful drinkers reported nonadherence, respectively (χ2(1) = 4.79, p = .029)). Multivariate logistic regression demonstrated that harmful alcohol use (AOR = 6.72, 95%CI = 1.49-30.33, p = .013) and moderate/high risk cocaine use (AOR = 3.11, 95%CI = 1.01-9.59, p = .049) independently predicted nonadherence. Furthermore, an additive association emerged, wherein the likelihood of PrEP nonadherence was highest among those who were hazardous/harmful drinkers and moderate/high risk cocaine users (OR = 2.25, 95%CI = 1.19-4.25, p = .013). Depression was not associated with nonadherence. CONCLUSIONS: Findings highlight the need to integrate alcohol- and substance-focused initiatives into PrEP care for gbMSM. Such initiatives, in turn, may help improve PrEP adherence and reduce the potential for HIV acquisition among this group.

Lower Blood Alcohol Concentration Among HIV-Positive Versus HIV-Negative Individuals Following Controlled Alcohol Administration.

BACKGROUND: Although it has been purported that HIV-positive individuals may experience a greater degree of intoxication than HIV-negative individuals following acute alcohol consumption, no research to date has empirically tested this supposition. The present investigation entailed a randomized controlled experiment to identify whether the administration of a weight-specified dose of alcohol would lead to differential blood alcohol concentrations (BACs) among HIV-positive versus HIV-negative men. METHODS: In a specialized barroom laboratory, 143 men (n = 76 HIV-positive and n = 67 HIV-negative; mean age = 42.9) consumed beverages based on a formulation of 0.7 g alcohol/kg body weight over a 15-minute time frame. BAC was assessed via breathalyzer at 2 set time points (10 and 13 minutes postconsumption) and then periodically until detoxification (BAC < 0.040%). Primary outcomes included (i) area under the curve (AUC), calculated based on all of one's BAC readings, (ii) "BAC-EXP," defined as one's BAC reading 13 minutes postconsumption, and (iii) BAC-PEAK, defined as one's highest recorded BAC reading. RESULTS: Contrary to predictions, AUC (t(141) = 2.23, p = 0.027), BAC-EXP (t(141) = 2.68, p = 0.008), and BAC-PEAK (t(141) = 2.29, p = 0.023) were significantly lower among HIV-positive versus HIV-negative participants. These effects were sustained in multivariable models controlling for age, race, and AUDIT-based hazardous drinking classification. Among the HIV-positive sample, outcomes did not significantly differ based on HIV viral load detectability, antiretroviral therapy (ART) status, or ART adherence. CONCLUSIONS: The administration of a controlled, weight-specified dose of alcohol led to lower BACs among HIV-positive versus HIV-negative participants. These differences might derive from decreased body fat percentage and delayed gastric emptying associated with HIV seropositivity; however, additional research is necessary to verify these mechanisms. Unique alcohol dosing formulas based on HIV serostatus may be required in future alcohol administration experiments involving HIV-positive samples.

HIV Risk and Protective Factors in the Context of Alcohol and Substance Use During Pride.

This investigation sought to identify HIV-risk and -protective factors among men-who-have-sex-with-men (MSM) who engaged in anal sex following alcohol or substance use during an international Pride Festival. MSM attending World Pride were surveyed regarding (1) alcohol, substance use, and sex during the past 24 h; and (2) HIV-risk and -protective factors. Valid data were provided by 1123 MSM. Anal sex was reported by 195 MSM, among whom the majority (n = 105) consumed alcohol or substances prior to sex. Among MSM aware of their HIV status who consumed alcohol or substances prior to sex (n = 99), those who engaged in serodiscordant condomless anal sex (n = 22) were more likely to be HIV+ (AOR = 10.14, 95% CI 1.48-69.35); report multiple sex partners (AOR = 9.05, 95% CI 1.70-48.12); and possess lower condom efficacy (AOR = 0.47, 95% CI 0.23-0.93) and social support (AOR = 0.08, 95% CI 0.01-0.46). Bolstering condom negotiation skills and social support could potentially reduce HIV acquisition/transmission-risk behavior, even when under the influence of alcohol or substances.

Protocol for a Controlled Experiment to Identify the Causal Role of Acute Alcohol Consumption in Condomless Sex among HIV-Positive MSM: Study Procedures, Ethical Considerations, and Implications for HIV Prevention.

Although alcohol consumption is frequently perceived as a driver of condomless sex and subsequent HIV acquisition, the causal nature of this relationship remains unclear, and little is known about alcohol's direct versus indirect impact on the sexual risk dynamics of those who are HIV-positive. To address this gap, we present the protocol for an in-progress NIAAA-funded controlled experiment, wherein a sample of HIV-positive men-who-have-sex-with-men (MSM) undergoes an alcohol consumption manipulation (alcohol/placebo/control) and sexual arousal induction (sexually aroused/non-aroused), and then reports intentions to engage in condom-protected and condomless sexual acts with hypothetical sexual partners differing in HIV serostatus (HIV+/HIV-/HIV status unknown), condom use preference (use/don't use/not stated), and physical attractiveness (attractive/unattractive). Study outcomes will identify alcohol's impact on HIV-positive MSM's condomless sex intentions in the context of experimentally-manipulated factors as well as risk-relevant personality traits and alcohol-related expectancies. Detailed experimental procedures, ethical considerations, and potential implications for HIV prevention are discussed.

Differential predictors of ART adherence among HIV-monoinfected versus HIV/HCV-coinfected individuals.

Although adherence is an important key to the efficacy of antiretroviral therapy (ART), many people living with HIV (PLWH) fail to maintain optimal levels of ART adherence over time. PLWH with the added burden of Hepatitis C virus (HCV) coinfection possess unique challenges that potentially impact their motivation and ability to adhere to ART. The present investigation sought to (1) compare ART adherence levels among a sample of HIV/HCV-coinfected versus HIV-monoinfected patients, and (2) identify whether ART-related clinical and psychosocial correlates differ by HCV status. PLWH receiving ART (N = 215: 105 HIV/HCV-coinfected, 110 HIV-monoinfected) completed a comprehensive survey assessing ART adherence and its potential correlates. Medical chart extraction identified clinical factors, including liver enzymes. Results demonstrated that ART adherence did not differ by HCV status, with 83.7% of coinfected patients and 82.4% of monoinfected patients reporting optimal (i.e., ≥95%) adherence during a four-day recall period (p = .809). Multivariable logistic regression demonstrated that regardless of HCV status, optimal ART adherence was associated with experiencing fewer adherence-related behavioral skills barriers (AOR = 0.56; 95%CI = 0.43-0.73), lower likelihood of problematic drinking (AOR = 0.15; 95%CI = 0.04-0.67), and lower likelihood of methamphetamine use (AOR = 0.14; 95%CI = 0.03-0.69). However, among HIV/HCV-coinfected patients, optimal adherence was additionally associated with experiencing fewer ART adherence-related motivational barriers (AOR = 0.23; 95%CI = 0.08-0.62) and lower likelihood of depression (AOR = 0.06; 95%CI = 0.00-0.84). Findings suggest that although HIV/HCV-coinfected patients may face additional, distinct barriers to ART adherence, levels of adherence commensurate with those demonstrated by HIV-monoinfected patients might be achievable if these barriers are addressed.

Personality as a predictor of unprotected sexual behavior among people living with HIV/AIDS: a systematic review.

The present investigation involved a systematic literature review to (1) identify associations between personality constructs and unprotected sex among people living with HIV/AIDS (PLWH); (2) assess patterns of direct versus indirect personality-risky sex associations; and (3) explore possible differences in personality-risky sex associations among PLWH versus non-infected populations. Among the 26 studies yielded through the systematic search, sensation seeking and sexual compulsivity were the constructs most frequently examined, with fewer studies investigating traditional personality typologies. Personality constructs that were more conceptually proximal to the sexual act, such as sexual compulsivity and sex-related sub-components of sensation seeking, showed relatively direct associations with unprotected sex, whereas more conceptually distal constructs such as generalized impulsivity demonstrated only weak or indirect associations. Associations were also frequently mediated by other risk factors, including perceived responsibility and substance use. These findings have implications for the development of interventions to reduce high risk sexual behavior among PLWH.

Causal considerations on alcohol and HIV/AIDS--a systematic review.

AIM: The study aimed to explore the possible causal nature of the association between alcohol consumption and HIV/AIDS. METHODS: A review based on meta-analyses and reviews was conducted according to standard epidemiological criteria to distinguish causality from association, examining (i) the potential impact of alcohol on the incidence of HIV and (ii) alcohol's impact on worsening the disease course. RESULTS: In terms of incidence of HIV, although we found a consistent and strong association with consumption, there was not enough evidence for a causal connection. In particular, it is not clear whether personality traits such as sensation seeking or sexual compulsivity and psychiatric disorders such as antisocial personality disorder impact both alcohol consumption and risky sex, subsequently creating an association between both behaviors. In terms of worsening the disease course of HIV/AIDS, we found enough evidence for a causal impact of alcohol. Alcohol affects the immune system, thus contributing to a worsened course of HIV/AIDS. In addition, alcohol negatively impacts on behaviors that include support seeking and medication adherence. CONCLUSIONS: A randomized controlled clinical trial targeted toward at-risk HIV-negative individuals who live in areas with high HIV prevalence is suggested to test the effects of proven effective alcohol interventions on HIV incidence.

Alcohol as a correlate of unprotected sexual behavior among people living with HIV/AIDS: review and meta-analysis.

The present investigation attempted to quantify the relationship between alcohol consumption and unprotected sexual behavior among people living with HIV/AIDS (PLWHA). A comprehensive search of the literature was performed to identify key studies on alcohol and sexual risk behavior among PLWHA, and three separate meta-analyses were conducted to examine associations between unprotected sex and (1) any alcohol consumption, (2) problematic drinking, and (3) alcohol use in sexual contexts. Based on 27 relevant studies, meta-analyses demonstrated that any alcohol consumption (OR = 1.63, CI = 1.39-1.91), problematic drinking (OR = 1.69, CI = 1.45-1.97), and alcohol use in sexual contexts (OR = 1.98, CI = 1.63-2.39) were all found to be significantly associated with unprotected sex among PLWHA. Taken together, these results suggest that there is a significant link between PLWHA's use of alcohol and their engagement in high-risk sexual behavior. These findings have implications for the development of interventions to reduce HIV transmission risk behavior in this population.

Acute Alcohol Consumption Directly Increases HIV Transmission Risk: A Randomized Controlled Experiment.

BACKGROUND: Alcohol consumption has frequently been purported as a driver of condomless sex and HIV transmission, but to date, experimental evidence for the causal risk-taking impact of alcohol among HIV-positive populations is lacking. The present experiment sought to determine whether acute alcohol consumption has a direct causal impact on condomless sex intentions among HIV-positive men-who-have-sex-with-men (MSM), and to assess whether alcohol's impact differs between MSM who are HIV-positive versus HIV-negative. METHODS: In a randomized controlled alcohol administration experiment, HIV-positive and HIV-negative MSM were brought into a specialized barroom laboratory and randomly assigned to beverage consumption condition: alcohol (target blood alcohol concentration = 0.080%), placebo alcohol (target blood alcohol concentration = 0.000%), or water (control). Participants then underwent a video-based sexual arousal manipulation (sexually aroused/nonaroused) and indicated their intentions to engage in condom-protected and condomless sexual acts in a standardized paradigm. The primary outcome entailed intentions to engage in condomless receptive and condomless insertive anal sex. RESULTS: A total of 282 MSM (141 HIV-positive; 141 HIV-negative) completed experimental procedures. MSM who received alcohol reported significantly stronger intentions to engage in condomless sex than those who received placebo alcohol or water (F(1,274) = 9.43, P = 0.002). The impact of alcohol did not differ between HIV-positive and HIV-negative MSM (F(1,274) = 1.86, P = 0.174). CONCLUSIONS: The present investigation entailed the first risk-focused alcohol administration experiment to involve an HIV-positive sample, and results demonstrated that consuming alcohol had an independent, causal impact on intentions to engage in sexual behaviors that can result in HIV transmission. Findings strongly suggest that alcohol-focused initiatives should be incorporated into HIV prevention efforts.

Alcohol consumption and the intention to engage in unprotected sex: systematic review and meta-analysis of experimental studies.

AIMS: To review and analyse in experimentally controlled studies the impact of alcohol consumption on intentions to engage in unprotected sex. To draw conclusions with respect to the question of whether alcohol has an independent effect on the incidence of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). METHODS: A systematic review and meta-analysis of randomized controlled studies examined the association between blood alcohol content (BAC) and self-perceived likelihood of using a condom during intercourse. The systematic review and meta-analysis were conducted according to internationally standardized protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses: PRISMA). The meta-analysis included an estimate of the dose-response effect, tests for publication bias and sensitivity analyses. RESULTS: Of the 12 studies included in the quantitative synthesis, our pooled analysis indicated that an increase in BAC of 0.1 mg/ml resulted in an increase of 5.0% (95% CI: 2.8-7.1%) in the indicated likelihood (indicated by a Likert scale) of engaging in unprotected sex. After adjusting for potential publication bias, this estimate dropped to 2.9% (95% CI: 2.0-3.9%). Thus, the larger the alcohol intake and the subsequent level of BAC, the higher the intentions to engage in unsafe sex. The main results were homogeneous, persisted in sensitivity analyses and after correction for publication bias. CONCLUSIONS: Alcohol use is an independent risk factor for intentions to engage in unprotected sex, and as risky sex intentions have been shown to be linked to actual risk behavior, the role of alcohol consumption in the transmission of HIV and other STIs may be of public health importance.

The anti-epileptic drug lacosamide (Vimpat) has anxiolytic property in rodents.

Lacosamide ((R)-2-acetamido-N-benzyl-3-methoxypropionamide; formerly harkoseride, SPM 927; Vimpat), has been recently approved by US and European regulatory authorities for use as add-on therapy for partial-onset seizures in adults. Because a number of anti-epileptic drugs are used to treat conditions beyond epilepsy, including anxiety, in the present study we investigated the anxiolytic potential of lacosamide in a conditioned emotional response (CER) model in rat, and the mouse marble burying assay. In each test lacosamide produced a significant effect consistent with anxiolysis, i.e. lacosamide increased suppression ratio in the CER test, and reduced the number of marbles buried in the marble burying assay. The doses necessary for an anxiolytic effect were higher than those necessary for efficacy in seizure tests conducted in the same species. For example in the mouse, the lacosamide oral ED(50) in the maximal electroshock seizure (MES) and 6 Hz tests was 5.3 and 9.6 mg/kg respectively, and the minimal effective dose in the marble burying assay was 30 mg/kg. In both seizure and anxiety tests, the (S)-enantiomer of lacosamide was inactive suggesting a similar mechanism of action, possibly use-dependent inhibition of sodium channel function (Errington et al., 2008). Efficacy in the CER model was equivalent to diazepam and pregabalin (Lyrica). In tests of side-effects, lacosamide had no effect on choice accuracy in the delayed match to position task of working memory, although at the 30 mg/kg dose, response rates and response latencies were significantly affected. In sum, the present results identify for the first time, an anxiolytic potential of lacosamide.