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The human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein forms a conical lattice around the viral ribonucleoprotein complex (vRNP) consisting of a dimeric viral genome and associated proteins, together constituting the viral core. Upon entry into target cells, the viral core undergoes a process termed uncoating, during which CA molecules are shed from the lattice. Although the timing and degree of uncoating are important for reverse transcription and integration, the molecular basis of this phenomenon remains unclear. Using complementary approaches, we assessed the impact of core destabilization on the intrinsic stability of the CA lattice in vitro and fates of viral core components in infected cells. We found that substitutions in CA can impact the intrinsic stability of the CA lattice in vitro in the absence of vRNPs, which mirrored findings from an assessment of CA stability in virions. Altering CA stability tended to increase the propensity to form morphologically aberrant particles, in which the vRNPs were mislocalized between the CA lattice and the viral lipid envelope. Importantly, destabilization of the CA lattice led to premature dissociation of CA from vRNPs in target cells, which was accompanied by proteasomal-independent losses of the viral genome and integrase enzyme. Overall, our studies show that the CA lattice protects the vRNP from untimely degradation in target cells and provide the mechanistic basis of how CA stability influences reverse transcription. [ABSTRACT FROM AUTHOR]

A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adversely affecting functional IN multimerization and consequently impairing IN binding to viral RNA; and (iii) directly compromising IN-RNA interactions without substantially affecting IN levels or functional IN multimerization. Inhibition of IN-RNA interactions resulted in the mislocalization of viral ribonucleoprotein complexes outside the capsid lattice, which led to premature degradation of the viral genome and IN in target cells. Collectively, our studies uncover causal mechanisms for the class II phenotype and highlight an essential role of IN-RNA interactions for accurate virion maturation. [ABSTRACT FROM AUTHOR]

Background: Substance use can reduce care engagement for individuals with HIV. However, little is known as to whether heavy drinkers differ from drug users. This study compares heavy drinkers, drug users, and those drinking heavily and using drugs on their HIV care engagement.Methods: HIV-infected adult inpatients (n = 801; 67% male; 78% Black) from 11 urban hospitals across the United States participated in a multisite clinical trial to improve patient engagement in HIV care and virologic outcomes. All participants drank heavily and/or used drugs, and had poorly controlled HIV. Participants reported care history at baseline. We compared heavy drinkers, drug users, and those both drinking heavily and using drugs (reference group) on their engagement in care.Results: Heavy drinkers reported lowest rates of lifetime HIV care, AOR = 0.59 (95% CI = 0.36, 0.97). Groups did not differ in recent care, prescription of HIV medication, medical mistrust, or patient-provider relationship. Drug users evidenced the best medication adherence, AOR = 2.38 (95% CI = 1.33, 4.23). Exploratory analyses indicated that drinkers had lower initial care engagement, but that it increased more rapidly with duration of known HIV infection, with similar rates of recent care. Drinkers had the lowest CD4 counts (B=-0.28, p < 0.0001), but no difference in viral load.Conclusions: Heavy drinkers were least likely to have ever been in HIV care. More research is needed to determine why heavy drinkers evidence the lowest initial care engagement and current CD4 counts, and whether drinking intervention early in infection may increase HIV care engagement. [ABSTRACT FROM AUTHOR]

Background: Heavy drinking poses health risks for individuals with HIV, and some individuals with HIV attempt to reduce drinking. Little is known about whether medical reasons motivate HIV-infected individuals to reduce drinking. Objectives: We evaluated medical reasons for limiting drinking among patients in a sexual health clinic, and explored whether these reasons could be operationalized as a new scale for research and clinical use in sexual health clinics. Methods: A sample of 70 patients in a sexual health clinic who reported efforts to limit drinking in the past month (84% with self-reported HIV; 81% male; 50% Black) completed a nine-item medical reasons for limiting drinking scale on a tablet while waiting for their appointment. Exploratory factor analysis was performed to evaluate psychometric properties of the scale. Results: Patients most commonly endorsed general concerns about health, and concerns about alcohol's effect on the liver. Support was found for a unidimensional (one-factor) eight-item scale, which evidenced good internal consistency (α = 0.84). Results were identical when analyses were restricted to the subset of 59 individuals who self-reported HIV infection. Conclusions/Importance: This study suggests that individuals in a sexual health clinic most commonly endorse broad nonspecific concerns about drinking and health, as well as concerns about their liver. This study yields an 8-item scale to measure medical reasons for limiting drinking in sexual health clinics and among individuals with HIV. This scale should enhance researchers' ability to study this important construct and may facilitate discussion of drinking reduction with HIV-infected heavy drinkers, requiring future study. [ABSTRACT FROM AUTHOR]

Aims We aimed to identify psychosocial factors related to problem drinking among patients with poorly controlled human immunodeficiency virus (HIV) infection. Short Summary We aimed to identify psychosocial factors related to problem drinking among those with poorly controlled HIV infection. Increased levels of interpersonal conflict were associated with greater severity of alcohol problems. Poorer mental health, medical mistrust and less satisfaction with one’s physician related to excessive drinking. Methods This secondary analysis used baseline data from a large multisite randomized controlled trial of substance users whose HIV infection was currently poorly controlled, from 11 urban hospitals across the USA. Participants were HIV-infected adult inpatients (n = 801; 67% male, 75% African American) with substance use histories. Participants self-reported on their drinking, perceived health, mental health, social relationships and patient–provider relationship. Structural equation models examined psychosocial factors associated with problem drinking, controlling for demographic covariates. Results Increased levels of interpersonal conflict were associated with greater severity of alcohol problems. Poorer mental health, medical mistrust and less satisfaction with one’s physician were associated with excessive drinking. Conclusions Several psychosocial factors, including interpersonal conflict, poor mental health (i.e. anxiety, depression and somatization), medical mistrust and less satisfaction with one’s provider, were associated with problem drinking among HIV-infected substance users with poorly controlled HIV infection. The co-occurrence of these concerns highlights the need for comprehensive services (including attention to problem drinking, social services, mental health and quality medical care) in this at-risk group. [ABSTRACT FROM AUTHOR]

Heavy drinking can cause medical problems for individuals with HIV, and drinking despite medical contraindications indicates problem use. However, little is known about which individuals with HIV drink despite knowledge of health problems. This study utilizes two subsamples of individuals with HIV from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III): those reporting at least one drink (a) in their lifetime (n = 205) or (b) in the past year (n = 166). Participants reported on drinking despite health problems and psychopathology in the past year and in their lifetime, and family history of alcohol problems. Individuals with a drug use disorder (Adjusted Odds Ratios [AORs] = 3.56-12.65), major depressive disorder (AORs = 10.18-10.55), or a family history of alcohol problems (AORs = 33.60-96.01) were more likely to drink despite health problems. Anxiety and personality disorders did not increase risk. Individuals with HIV with drug use disorders or major depressive disorder are more likely to drink despite health problems. Individuals with a family history of alcohol problems were also more likely to do so, although further research is needed given large confidence intervals. Future research should consider how to help these individuals avoid alcohol-related harm. [ABSTRACT FROM AUTHOR]

Background: Individuals who use illicit drugs are at heightened risk for HIV and/or Hepatitis C Virus (HCV). Despite the medical consequences of drinking for drug-using individuals with these infections, many do drink. In other studies, how individuals perceive their health relates to their engagement in risk behaviors such as drinking. However, among drug-using individuals with HIV and HCV, whether perceived health relates to drinking is unknown.Objective: We examine the association between perceived health and drinking among drug-using individuals with HIV and/or HCV.Methods: In a large, cross-sectional study, we utilized samples of individuals with HIV (n=476), HCV (n=1145), and HIV/HCV co-infection (n=180), recruited from drug treatment centers from 2005 to 2013. In each sample, we investigated the relationship between perceived health and drinking, using ordinal logistic regressions. We present uncontrolled models as well as models controlled for demographic characteristics.Results: Among samples of drug using individuals with HIV and with HCV, poorer perceived health was associated with risky drinking only when demographic characteristics were taken into account (Adjusted Odds Ratios: 1.32 [1.05, 1.67] and 1.16 [1.00, 1.34], respectively). In the smaller HIV/HCV co-infected sample, the association of similar magnitude was not significant (AOR=1.32 [0.90, 1.93]).Conclusions: Drug using patients with HIV or HCV with poor perceived health are more likely to drink heavily, which can further damage health. However, when demographics are not accounted for, these effects can be masked. Patients' reports of poor health should remind providers to assess for health risk behaviors, particularly heavy drinking. [ABSTRACT FROM AUTHOR]

Objective: Among drug users with HIV and Hepatitis C Virus (HCV) infections, heavy drinking can pose significant risks to health. Yet many drug users with HIV and HCV drink heavily. Clarifying the relationship of drug-using patients' understanding of their illnesses to their drinking behavior could facilitate more effective intervention with these high-risk groups.Method: Among samples of drug users infected with HIV (n=476; 70% male) and HCV (n=1145; 81% male) recruited from drug treatment clinics, we investigated whether patients' perceptions of the risk for severe outcomes related to HIV and HCV were associated with their personal drinking behavior, using generalized logit models. Interactions with co-infection status were also explored.Results: HIV-infected drug users who believed that HIV held highest risk for serious outcomes were the most likely to be risky drinkers, when compared with those with less severe perceptions, X(2)(6)=14.19, p<0.05. In contrast, HCV-infected drug users who believed that HCV held moderate risk for serious outcomes were the most likely to be risky drinkers, X(2)(6)=12.98, p<0.05.Conclusions: In this sample of drug users, risky drinking was most common among those with HIV who believed that severe outcomes were inevitable, suggesting that conveying the message that HIV always leads to severe outcomes may be counterproductive in decreasing risky drinking in this group. However, risky drinking was most common among those with HCV who believed that severe outcomes were somewhat likely. Further research is needed to understand the mechanisms of these associations. [ABSTRACT FROM AUTHOR]

Introduction:Heavy drinking can be harmful for individuals with HIV, particularly those coinfected with hepatitis C virus (HCV). HIV patients’ reasons for drinking predict short-term alcohol involvement, but whether they predict longer-term involvement is unknown. Also, it remains unknown whether these motives are differentially predictive for HIV monoinfected and HIV/HCV coinfected patients. Method:HIV-infected heavy drinkers (n = 254) participated in a randomized trial of brief alcohol interventions, 236 (92.9%) of whom reported on baseline motives and alcohol involvement 12 months later (77.1% male, 94.9% minority, 30.6% with HCV). Results:Greater endorsement of baseline drinking to cope with negative affect predicted greater alcohol dependence symptoms at 12 months (incident rate ratio [IRR] = 1.80, p < 0.05), while greater endorsement of baseline drinking due to social pressure predicted fewer drinks consumed at 12 months (IRR = 0.67, p < 0.05). Coping and social reasons were both predictive for HIV monoinfected patients, whereas only coping reasons were predictive for HIV/HCV coinfected patients. Discussion:Drinking for coping and social reasons predict alcohol involvement 12 months later; however, social reasons may only be important for HIV monoinfected patients. Understanding patient reasons for drinking may help predict patient risk up to a year later.KEY MESSAGESAmong HIV patients, drinking motives predict alcohol involvement 12 months later.For HIV monoinfected patients, drinking to cope and drinking for social reasons predict 12-month alcohol involvement.For HIV/Hepatitis C coinfected patients, coping (but not social) motives predict 12-month alcohol involvement. [ABSTRACT FROM PUBLISHER]

Background Heavy alcohol consumption can be harmful, particularly for individuals with HIV. There is substantial variability in response to interventions that aim to reduce drinking. Neighborhood drinking norms may explain some of this variability among HIV-infected patients. Therefore, we investigated whether neighborhood-level drinking norms modified response to alcohol intervention among HIV-infected heavy drinkers. Methods Heavily-drinking HIV comprehensive care patients ( n = 230) completed 1 of 3 brief alcohol interventions (an educational intervention, a motivational interviewing [ MI] intervention, or an MI intervention with a technological enhancement called HealthCall). Drinking was reported at baseline and end of treatment (60 days). Neighborhood-level drinking norms were obtained from a separate general population study. Results Patients' reductions in drinks per drinking day in response to MI (as compared with the educational control) were more pronounced in neighborhoods with more permissive drinking norms. In contrast, patients' reductions in drinks per drinking day in response to MI plus HealthCall did not significantly vary between neighborhoods with different drinking norms. Norms did not evidence significant interactions with intervention condition for 3 other exploratory drinking outcomes (drinking frequency, binge frequency, and maximum quantity). Conclusions Neighborhood-level drinking norms help explain differential response to an alcohol MI intervention among HIV-infected patients. This study suggests the utility of considering neighborhood context as an effect modifier of alcohol interventions. [ABSTRACT FROM AUTHOR]

Background For individuals with HIV, heavy drinking can pose serious threats to health. Some interventions are effective at reducing drinking in this population, but many HIV-infected heavy drinkers also use marijuana or cocaine. Although these drugs have predicted poor alcohol outcomes in other treatment studies, whether this occurs among HIV patients who drink heavily is unknown. Methods Participants were binge-drinking HIV primary care patients ( N = 254) enrolled in a randomized trial of three brief drinking interventions over 60 days that varied in intensity. We investigated the relationship of baseline past-year drug use (marijuana-only, cocaine-only, both, neither) to end-of-treatment drinking quantity and frequency. We also evaluated whether the relationship between intervention type and end-of-treatment drinking varied by baseline drug use. Final models incorporated control for patients’ demographic and HIV characteristics. Results In final models, drinking frequency at the end of treatment did not vary by baseline drug use, but drinking quantity did ( X 2 [3] = 13.87, p < 0.01), with individuals using cocaine-only drinking significantly more per occasion ( B = 0.32, p < 0.01). Baseline drug use also interacted with intervention condition in predicting end-of-treatment drinking quantity ( X 2 [6] = 13.98, p < 0.05), but not frequency, with the largest discrepancies in end-of-treatment drinks per drinking day by intervention intensity among cocaine-only patients. Conclusions In general, HIV patients using cocaine evidenced the highest levels of drinking after alcohol intervention. However, these individuals also evidenced the most pronounced differences in end-of-treatment drinking by intervention intensity. These results suggest the importance of more intensive intervention for individuals using alcohol and cocaine. [ABSTRACT FROM AUTHOR]

Background Heavy drinking poses significant risks to the health and survival of individuals infected with HIV, particularly those coinfected with hepatitis C virus ( HCV). However, little is known about patients' perceptions of these risks, and whether these perceptions relate to their alcohol consumption. Methods A sample of 254 heavily drinking HIV primary care patients (78% male; 94.5% minority; 31.8% with HCV) reported on their perceptions of the medical risks of drinking and on their alcohol consumption prior to participation in a drinking-reduction intervention trial. Results In the HIV-infected sample as a whole, 62.9% reported that they had a medical problem made worse by drinking, and 64.3% reported restricting drinking to avoid future medical problems. Although patients coinfected with HIV/ HCV reported greater efforts to restrict drinking to avoid future medical problems (adjusted odds ratio = 1.94), their reported drinking quantity and frequency did not differ from that of HIV mono-infected patients. Awareness of medical risk was not associated with drinking level. Effort to restrict drinking to avoid medical risk was associated with lower drinking quantity, frequency, and binge frequency ( ps < 0.05), but the association with binge frequency was specific to patients without HCV. Conclusions Over one-third of HIV patients are unaware of the medical risks of drinking, and do not restrict use, suggesting the need for intervention in this group. Patients coinfected with HIV/ HCV may report more effort to restrict drinking, but their reported drinking quantity and frequency suggest that they are actually drinking just as heavily as HIV mono-infected patients. Awareness of medical risk was unrelated to drinking, which suggests the need for interventions consisting of more than simple education. However, reported effort to restrict drinking did predict less drinking, suggesting the importance of patient commitment and initiative in change. [ABSTRACT FROM AUTHOR]

Background Heavy drinking among individuals with HIV is associated with major health concerns (liver disease, medication nonadherence, immune functioning), but little is known about cognitive-motivational factors involved in alcohol consumption in this population, particularly reasons for limiting drinking. Methods Urban HIV primary care patients ( N = 254; 78.0% male; 94.5% African American or Hispanic) in a randomized trial of brief drinking-reduction interventions reported on reasons for limiting drinking, alcohol consumption, and alcohol dependence symptoms prior to intervention. Results Exploratory factor analysis indicated 3 main domains of reasons for limiting drinking: social reasons (e.g., responsibility to family), lifestyle reasons (e.g., religious/moral reasons), and impairment concerns (e.g., hangovers). These factors evidenced good internal consistency ( αs = 0.76 to 0.86). Higher scores on social reasons for limiting drinking were associated with lower typical quantity, maximum quantity, and binge frequency ( ps < 0.01), and higher scores on lifestyle reasons were associated with lower maximum quantity, binge frequency, and intoxication frequency ( ps < 0.01). In contrast, higher scores on impairment concerns were associated with more frequent drinking and intoxication, and higher risk of alcohol dependence ( ps < 0.05), likely because dependent drinkers are more familiar with alcohol-induced impairment. Conclusions The current study is the first to explore reasons for limiting drinking among individuals with HIV and how these reasons relate to alcohol involvement. This study yields a scale that can be used to assess reasons for limiting drinking among HIV-positive drinkers and provides information that can be used to enhance interventions with this population. Discussing social and lifestyle reasons for limiting drinking among less extreme drinkers may support and validate these patients' efforts to limit engagement in heavy drinking; discussion of impairment reasons for limiting drinking may be a way to engage dependent drinkers in efforts to decrease their alcohol consumption. [ABSTRACT FROM AUTHOR]

Abstract: Background: Heavy alcohol consumption in HIV patients is an increasing health concern. Applying the drinking motivational model to HIV primary care patients, drinking motives (drinking to cope with negative affect, for social facilitation, and in response to social pressure) were associated with alcohol consumption at a baseline interview. However, whether these motives predict continued heavy drinking or alcohol dependence in this population is unknown. Methods: Participants were 254 heavy-drinking urban HIV primary care patients (78.0% male; 94.5% African American or Hispanic) participating in a randomized trial of brief drinking-reduction interventions. Drinking motive scales, as well as measures of alcohol consumption and alcohol dependence, were administered at baseline. Consumption and dependence measures were re-administered at the end of treatment two months later. Regression analyses tested whether baseline drinking motive scale scores predicted continued heavy drinking and alcohol dependence status at the end of treatment, and whether motives interacted with treatment condition. Results: Baseline drinking to cope with negative affect predicted continued heavy drinking (p <0.05) and alcohol dependence, the latter in both in the full sample (adjusted odds ratio [AOR]=2.14) and among those with baseline dependence (AOR=2.52). Motives did not interact with treatment condition in predicting alcohol outcomes. Conclusions: Drinking to cope with negative affect may identify HIV patients needing targeted intervention to reduce drinking, and may inform development of more effective interventions addressing ways other than heavy drinking to cope with negative affect. [Copyright &y& Elsevier]

Abstract We used the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III), a nationally representative sample of US adults (n = 34,653), to estimate the prevalence and correlates of HIV testing and HIV status. The diagnostic interview used was the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-5 Version. We found that in 2012–2013, the prevalence of a history of HIV testing was 53.0% among females and 47.0% among males. Among individuals tested, the prevalence of HIV was 1.06%, resulting in a known estimated prevalence of 0.54% in the full sample. In adjusted results, being non-white, aged 30–44, having college, being non-heterosexual, having history of unprotected sex or history of childhood sexual abuse and lower mental health-related quality of life increased the odds of having been tested, whereas being foreign-born, 45 years or older, family income ≥$20,000, being unemployed or a student, living in a rural setting and older age at first sex lowered those odds. Among those tested, being 30–64, being non-heterosexual, having history of unprotected sex or having a sexually transmitted disease in the last year was associated with greater odds of being HIV+. Having some college decreased those odds. In the adjusted results all psychiatric disorders were associated with increased rates of HIV testing, but only a lifetime history of drug use disorder and antisocial personality disorders were associated with HIV status among those tested. Despite CDC recommendations, only about half of US adults have ever been tested for HIV, interfering with efforts to eradicate HIV infection. [ABSTRACT FROM AUTHOR]

Introduction: Heavy drinking among people living with HIV (PLWH) worsens their health outcomes and disrupts their HIV care. Although brief interventions to reduce heavy drinking in primary care are effective, more extensive intervention may be needed in PLWH with moderate-to-severe alcohol use disorder. Lengthy interventions are not feasible in most HIV primary care settings, and patients seldom follow referrals to outside treatment. Utilizing visual and video features of smartphone technology, we developed the "HealthCall" app to provide continued engagement after brief intervention, reduce drinking, and improve other aspects of HIV care with minimal demands on providers. We conducted a randomized trial of its efficacy.Methods: The study recruited alcohol-dependent PLWH (n = 114) from a large urban HIV clinic. Using a 1:1:1 randomized design, the study assigned patients to: Motivational Interviewing (MI) plus HealthCall (n = 39); NIAAA Clinician's Guide (CG) plus HealthCall (n = 38); or CG-only (n = 37). Baseline MI and CG interventions took ~25 min, with brief (10-15 min) 30- and 60-day booster sessions. HealthCall involved daily use of the smartphone app (3-5 min/day) to report drinking and health in the prior 24 h. Outcomes assessed at 30 and 60 days and at 3, 6 and 12 months included drinks per drinking day (DpDD; primary outcome) and number of drinking days, analyzed with generalized linear mixed models and pre-planned contrasts.Results: Study retention was excellent (85%-94% across timepoints). At 30 days, DpDD among patients in MI + HealthCall, CG + HealthCall, and CG-only was 3.80, 5.28, and 5.67, respectively; patients in MI + HealthCall drank less than CG-only and CG + HealthCall (IRRs = 0.62, 95% CI = 0.46, 0.84, and 0.64, 95% CI = 0.48, 0.87, respectively). At 6 months (end-of-treatment), DpDD was lower in CG + HealthCall (DpDD = 4.88) than MI + HealthCall (DpDD = 5.88) or CG-only (DpDD = 6.91), although these differences were not significant. At 12 months, DpDD was 5.73, 5.31, and 6.79 in MI + HealthCall, CG + HealthCall, and CG-only, respectively; DpDD was significantly lower in CG + HealthCall than CG-only (IRR = 0.71, 95% CI = 0.51, 0.98).Conclusions: During treatment, patients in MI + HealthCall had lower DpDD than patients in other conditions; however, at 12 months, drinking was lowest among patients in CG + HealthCall. Given the importance of drinking reduction and the low costs/time required for HealthCall, pairing HealthCall with brief interventions merits widespread consideration. [ABSTRACT FROM AUTHOR]