HealthCall: Smartphone Enhancement of Brief Interventions to Improve HIV Medication Adherence Among Patients in HIV Care.

Heavy drinking among people living with HIV (PLWH) reduces ART adherence and worsens health outcomes. Lengthy interventions are not feasible in most HIV care settings, and patients infrequently follow referrals to outside treatment. Utilizing visual and video features of smartphone technology, we developed HealthCall as an electronic means of increasing patient involvement in a brief intervention to reduce drinking and improve ART adherence. The objective of the current study is to evaluate the efficacy of HealthCall to improve ART adherence among PLWH who drink heavily when paired with two brief interventions: the National Institute on Alcoholism and Alcohol Abuse (NIAAA) Clinician's Guide (CG) or Motivational Interviewing (MI). Therefore, we conducted a 1:1:1 randomized trial among 114 participants with alcohol dependence at a large urban HIV clinic. Participants were randomized to one of three groups: (1) CG only (n = 37), (2) CG and HealthCall (n = 38), or (3) MI and HealthCall (n = 39). Baseline interventions targeting drinking reduction and ART adherence were ~ 25 min, with brief (10-15 min) booster sessions at 30 and 60 days. The outcome was ART adherence assessed using unannounced phone pill-count method (possible adherence scores: 0-100%) at 30-day, 60-day, 3, 6, and 12 months. Analyses were conducted using generalized linear mixed models with pre-planned contrasts. Of the 114 enrolled patients, 58% were male, 75% identified as Black/African American, 28% were Hispanic, and 62% had less than a high school education. The mean age was 47.5 years (standard deviation [SD] 10 years) and the mean number of years since they were diagnosed with HIV was 18.6 (SD 7.6). Participants assigned to HealthCall to extend the CG had increased levels of ART adherence at 60-day and 6-month follow-up (compared to CG only), although there was no statistically significant difference by 12-month follow-up. Participants who were assigned to HealthCall to extend the MI never had statistically significant higher levels of ART adherence. These results suggest that the use of a smartphone app can be used to initially extend the reach of a brief drinking intervention to improve ART adherence over a short period of time; however, sustained long-term improvements in ART adherence after intervention activity ends remains a challenge.

Functional impairment is associated with medical debt in male cancer survivors and credit card debt in female cancer survivors.

PURPOSE: To examine the associations of functional limitations with medical and credit card debt among cancer survivor families and explore sex differences in these associations. METHODS: This cross-sectional study used data from the 2019 wave of the Panel Study of Income Dynamics, a nationally representative, population-based survey of individuals and households in the US administered in both English and Spanish and includes all households where either the head of household or spouse/partner reported having been diagnosed with cancer. Participants reported on functional limitations in six instrumental activities of daily living (IADL) and seven activities of daily living (ADL). Functional impairment was categorized as 0, 1-2 and ≥ 3 limitations. Medical debt was defined as self-reported unpaid medical bills. Credit card debt was defined as revolving credit card debt. Multivariable logistic regression analyses were performed. RESULTS: Credit card debt was more common than medical debt (39.8% vs. 7.6% of cancer survivor families). Families of male cancer survivors were 7.3 percentage points more likely to have medical debt and 16.0 percentage points less likely to have credit card debt compared to families of female cancer survivors. Whereas male cancer survivors with increasing levels of impairment were 24.7 percentage point (p-value = 0.006) more likely to have medical debt, female survivors with more functional impairment were 13.6 percentage points (p-value = 0.010) more likely to have credit card debt. CONCLUSIONS: More research on medical and credit card debt burden among cancer survivors with functional limitations is needed.

Analysis of school-based asthma screenings and need for care coordination in underserved urban communities.

BACKGROUND: Asthma is one of the most common chronic childhood disease states in the United States and continues to become more prevalent. Data suggest the incidence, morbidity, and mortality of asthma are higher among minority children of lower socioeconomic status living in urban settings. There is a lack of data evaluating the impact of mass school-based asthma screenings and care coordination in underserved communities. OBJECTIVE: This study aimed to determine whether a school-based asthma screening program is effective in identifying children who are at risk of undiagnosed and uncontrolled asthma and whether there is a need for care coordination. METHODS: This study is a retrospective review describing the outcomes of the 2021 school-based asthma screening program. Asthma screening data from 6 participating school districts (prekindergarten to twelfth grade) in the greater Pittsburgh area were included in this review. An asthma screening questionnaire was distributed school-wide and included questions about demographics, previous asthma diagnosis, repeated episodes of asthma, and frequency of symptoms. Based on caregiver-reported answers, children who screened positive for previously diagnosed asthma, uncontrolled asthma, or undiagnosed asthma received care coordination for follow-up care. RESULTS: This study included asthma screening results for 561 participants. Approximately 13% of participants (n = 73) displayed asthma symptoms but did not have a diagnosis of asthma. Of those 73 participants, 9.6% (n = 54) were at risk of uncontrolled asthma. The screening tool also identified 5.6% of participants (n = 32) who had a diagnosis of asthma and were at risk of uncontrolled asthma. CONCLUSIONS: The school-based asthma screening program was effective in identifying children at risk of undiagnosed and uncontrolled asthma. Pharmacists are well positioned to implement asthma screening programs in schools and throughout the community.

Disease and debt: Findings from the 2019 Panel Study of Income Dynamics in the United States.

Medical debt has grown dramatically over the past few decades. While cancer and diabetes are known to be associated with medical debt, little is known about the impact of other medical conditions and health behaviors on medical debt. We analyzed cross-sectional data on 9174 households - spanning lower-income, middle-income, and higher-income based on the Census poverty threshold - participating in the 2019 wave of the nationally representative United States Panel Study of Income Dynamics (PSID). The outcomes were presence of any medical debt and presence of medical debt≥ $2000. Respondents reported on medical conditions (diabetes, cancer, heart disease, chronic lung disease, asthma, arthritis, anxiety disorders, mood disorders) and on health behaviors (smoking, heavy drinking). Medical debt was observed in lower-income households with heart disease (OR = 2.64, p-value = 0.006) and anxiety disorders (OR = 2.16, p-value = 0.02); middle-income households with chronic lung disease (OR = 1.73, p-value = 0.03) and mood disorders (OR = 1.53, p-value = 0.04); and higher-income households with a current smoker (OR = 2.99, p-value<0.001). Additionally, medical debt ≥$2000 was observed in lower-income households with asthma (OR = 2.16, p-value = 0.009) and a current smoker (OR = 1.62, p-value = 0.04); middle income households with hypertension (OR = 1.65, p-value = 0.05). These novel findings suggest that the harms of medical debt extend beyond cancer, diabetes and beyond lower-income households. There is an urgent need for policy and health services interventions to address medical debt in a wider range of disease contexts than heretofore envisioned. Intervention development would benefit from novel conceptual frameworks on the causal relationships between health behaviors, health conditions, and medical debt that center social-ecological influences on all three of these domains.

Asthma prevalence and control among schoolchildren residing near outdoor air pollution sites.

INTRODUCTION: Outdoor air pollution (OAP) contributes to poor asthma outcomes and remains a public health concern in Pittsburgh. The purpose of this study was to determine the prevalence of childhood asthma and its rate of control among Pittsburgh schoolchildren residing near OAP sites. METHODS: Participants were recruited from schools near OAP sites. Asthma prevalence and control were assessed using a validated survey. Demographics and socioeconomic status were collected by survey, BMI was calculated, secondhand smoke (SHS) exposure was assessed by salivary cotinine levels, and OAP was assessed by mobile platform monitoring. Multivariate analysis adjusted for confounders. RESULTS: In 1202 Pittsburgh elementary school students surveyed, 50.9% were female, average age was 8.5 years (SD = 1.9), 52.2% were African American and 60.6% had public health insurance. SHS exposure was relatively high at 33.9%, 17.1% of students were obese, and 70% had exposure to particulate matter (PM2.5) greater than the World Health Organization standard of 10 µg/m3. Overall prevalence of asthma was 22.5% with PM2.5, nitric oxide (NOx), sulfur (S), and zinc (Zn) significantly related to odds of asthma. Among the 270 children previously diagnosed with asthma, 59.3% were not well controlled with PM2.5, black carbon, and silicon (Si) significantly related to odds of uncontrolled asthma. CONCLUSIONS: These results demonstrate that asthma prevalence and poor disease control are significantly elevated in Pittsburgh schoolchildren exposed to high levels of OAP. Future efforts need to focus on primary prevention of asthma by reducing exposure to OAP in at risk populations.

Relationship between interoceptive sensibility, age, and COVID-19 anxiety during the first national lockdown in the United Kingdom.

Objectives: Interoception refers to the multidimensional representation of the internal states of the body, including sensation, appraisal, integration, and regulation. COVID-19 targets internal respiratory, temperature and gastrointestinal systems, thus posing a threat to humans that causes anxiety. Here, we examined the relationship between interoceptive sensibility and COVID-19 anxiety during the first UK national lockdown, when uncertainties surrounding the virus were at their peak.Methods: Between April and July 2020, N = 232 individuals across four age-categories completed questionnaires measuring interoceptive sensibility (BPQ-SF and MAIA-2), an adapted State-Trait-Anxiety Inventory (STAI) to assess COVID-19 anxiety, and a Perceived Quality of Life (QoL) questionnaire.Results: Higher scores on the BPQ-SF were related to higher levels of COVID-19 anxiety, while the MAIA-2 subscales Not Worrying, Attention Regulation, and Trusting of bodily signals were related to lower levels of COVID-19 anxiety. Age was related to lower levels of COVID-19 anxiety yet showed no significant (Bonferroni-corrected) relationship with interoceptive dimensions. Trait anxiety, Not Worrying, perceived quality of work, and COVID-19-related media consumption emerged as significant predictors of COVID-19 anxiety.Conclusion: Findings suggest that interoceptive dimensions differentially relate to COVID-19 anxiety irrespective of age, with implications for managing health anxiety and adaptive behaviour during a pandemic across the lifespan.

Improved asthma outcomes among at-risk children in a pharmacist-led, interdisciplinary school-based health clinic: A pilot study of the CAReS program.

BACKGROUND: Disparities in access to care and outcomes have been identified among children with asthma living in underserved communities. The Caring for Asthma in our Region's Schoolchildren program was established to reduce disparities by providing school-based, comprehensive asthma care by a pharmacist-led, interdisciplinary team to high-risk pediatric populations in the Greater Pittsburgh area. OBJECTIVE: To investigate program impact on follow-up appointment attendance, delivery of guideline-based care, asthma control, asthma morbidity (emergency department [ED] visits, oral corticosteroid [OCS] requirement), and asthma-related knowledge and quality of life. METHODS: The study enrolled 50 children with asthma from 6 elementary schools (September 2014-December 2017). Children completed 5 visits over a 3-month period. McNemar's test assessed improvement in guideline-based controller therapy use and reduced morbidity (ED visits or OCS requirement). Generalized estimating equation analyses determined the significance of monthly improvements in asthma control, asthma knowledge, and quality of life. RESULTS: A 100% show rate was achieved in nearly all participants (92.0%). Most of the patients were African-American (56%). In children with persistent disease, only 21.4% were prescribed controller therapy at baseline, which improved to 78.5% upon enrollment (P < 0.05). Asthma control statistically significantly improved (P < 0.05), and a reduction in percentage of patients who required an ED visit or an OCS burst pre-to postintervention was also statistically significant (31.3% vs. 14.6%, P < 0.05). The goal of 100% treatment plan knowledge was achieved in 67% of caregivers within 1 month and increased from 6% to 60% in children over 3 months (P < 0.05). Asthma-related quality of life also improved statistically significantly pre-to postintervention (P < 0.05). CONCLUSIONS: Disparities in asthma outcomes owing to inadequate access to health care can be addressed. Improved asthma control, asthma medication knowledge, quality of life, and reduced morbidity in high-risk pediatric patients are achievable as demonstrated by our study. Our findings support the feasibility and value of a pharmacist-led, interdisciplinary school-based health care delivery model in providing comprehensive asthma care to at-risk pediatric populations.

Capsid Lattice Destabilization Leads to Premature Loss of the Viral Genome and Integrase Enzyme during HIV-1 Infection.

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.IMPORTANCE The human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein forms a conical lattice around the viral RNA genome and the associated viral enzymes and proteins, together constituting the viral core. Upon infection of a new cell, viral cores are released into the cytoplasm where they undergo a process termed "uncoating," i.e., shedding of CA molecules from the conical lattice. Although proper and timely uncoating has been shown to be important for reverse transcription, the molecular mechanisms that link these two events remain poorly understood. In this study, we show that destabilization of the CA lattice leads to premature dissociation of CA from viral cores, which exposes the viral genome and the integrase enzyme for degradation in target cells. Thus, our studies demonstrate that the CA lattice protects the viral ribonucleoprotein complexes from untimely degradation in target cells and provide the first causal link between how CA stability affects reverse transcription.

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma.

Aim: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. Results: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events. Conclusion: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1. Clinical trial registration: NCT02761187 (ClinicalTrials.gov).

Lay abstract Proteasome inhibitors are drugs used in multiple myeloma (MM), a blood cancer that develops from cells in the bone marrow. Ixazomib is the first oral proteasome inhibitor to be approved for use in MM, when given in combination with two other oral drugs, lenalidomide and dexamethasone, to adult patients who have received one prior therapy. Our study, which was conducted in routine clinical practice, found that the effectiveness and safety of ixazomib + lenalidomide + dexamethasone in previously treated MM patients were similar to those seen in the Phase III clinical trial on which approval was based. These findings are important because they suggest that MM patients in everyday practice can achieve the same benefits from this treatment as patients in clinical trials, despite often being in poorer health.

Financial hardship among cancer survivors in Southern New Jersey.

PURPOSE: To identify predictors of financial hardship, operationalized as foregoing health care, making financial sacrifices, and being concerned about having inadequate financial and insurance information. METHODS: Cancer survivors (n = 346) identified through the New Jersey State Cancer Registry were surveyed from August 2018 to September 2019. Multivariable logistic regression analyses were performed. RESULTS: Cancer survivors with household incomes less than $50,000 annually were more likely than those earning $50,0000-$90,000 to report foregoing health care (15.8 percentage points, p < 0.05). Compared to retirees, survivors who were currently unemployed, disabled, or were homemakers were more likely to forego doctor's visits (11.4 percentage points, p < 0.05), more likely to report borrowing money (16.1 percentage points, p < 0.01), and more likely to report wanting health insurance information (25.7 percentage points, p < 0.01). Employed survivors were more likely than retirees to forego health care (16.8 percentage points, p < 0.05) and make financial sacrifices (20.0 percentage points, p < 0.01). Survivors who never went to college were 9.8 percentage points (p < 0.05) more likely to borrow money compared to college graduates. Black survivors were more likely to want information about dealing with financial and insurance issues (p < 0.01); men were more likely to forego health care (p < 0.05). CONCLUSION: Findings highlight the role of employment status and suggest that education, income, race, and gender also shape cancer survivors' experience of financial hardship. There is a need to refine and extend financial navigation programs. For employed survivors, strengthening family leave policies would be desirable.

Pharmacist Involvement in Addressing Public Health Priorities and Community Needs: The Allegheny County Racial and Ethnic Approaches to Community Health (REACH) Project.

Community-clinical linkages are connections between community and clinical sectors to improve population health, and community-based pharmacists are well positioned to implement this strategy. We implemented a novel approach to community-clinical linkages in African American communities in which community-based pharmacists implement screenings for chronic disease and social determinants of health, make referrals to clinical and social services, and follow up with patients to support linkage to care in nontraditional health care settings. The community-based pharmacist navigation program works with multisector partners to increase referrals and access to existing health and social service programs. We used a mixed-methods evaluation approach to collect and analyze data on program characteristics and the linkage intervention. From February 2019 to March 2020, 702 African American community members received preventive health screenings, and 508 (72%) were referred to clinical and social services. Pharmacists demonstrated the ability to implement clinical preventive services in nontraditional health care settings and improve access to care through the provision of community-clinical linkages.

Substance use in a sexual context: The association of sex-related substance use motives with substance choice and use behaviors.

BACKGROUND: Substance use before sex is associated with riskier behaviors. Sex-related substance use motives may explain pre-sex substance use. We explored what sex-related motives are associated with alcohol versus drug use, and which motives underlie heavier use. METHODS: A sample of 936 participants (50% male, 80% White) completed an Internet survey about sexuality. Those who drank before sex (n=657) reported on six sex-related drinking motives; those who used drugs before sex (n=271) reported on six (parallel) sex-related drug use motives. The frequency of endorsement of each motive between drinkers and drug users was compared with z-distributions. Logistic regressions assessed whether motives were associated with substance use frequency and intoxication before sex. RESULTS: Substance use to relax and to get a sex partner to use were more commonly endorsed for alcohol than drugs; substance use to improve performance and enhance experience were more commonly endorsed for drugs. Most motives were associated with alcohol frequency and intoxication before sex. None were associated with drug frequency; some were associated with drug intoxication. CONCLUSIONS: Alcohol was generally used to facilitate sex, and drugs to enhance sex. Sex-related drinking motives were associated with drinking before sex; sex-related drug use motives were less predictive.

Low persistence to rivaroxaban or warfarin among patients with new venous thromboembolism at a safety net academic medical center.

Recent guidelines recommend direct acting oral anticoagulants (DOAC) over vitamin-k antagonist (VKA) for acute venous thromboembolism (VTE). Non-adherence to anticoagulation has been associated with increased frequency of VTE or stroke. This study evaluated 90 day persistence among patients prescribed rivaroxaban or warfarin for the treatment of acute VTE at an academic safety net hospital. We conducted a single center, retrospective cohort study of 314 consecutive patients newly prescribed rivaroxaban or warfarin for acute VTE between January 2016 and July 2017. Primary outcome was 90 day persistence, and secondary outcomes included 90 day readmission and/or ED visit, time to 90 m day readmission and/or ED visits, and attendance of direct oral anticoagulant education class. Of 314 patients, 78 were prescribed warfarin and 236 rivaroxaban. Patients had a mean age of 52 years, 62% were men, and 96% were diagnosed with deep vein thrombosis and/or pulmonary embolism. Persistence at 90 days was 52.6% among patients prescribed warfarin compared to 45.3% for patients prescribed rivaroxaban (p = 0.2678). Persistencewas associated with decreased 90 day hospital or ED readmission. Among patients prescribed rivaroxaban, attending a pharmacist led educational class was associated with a 2.5 fold increase in persistence (p < 0.0001). Among patients with new onset venous thromboembolism, 90 day persistence with anticoagulation was similarly low with either rivaroxaban or warfarin therapy. Participation in a pharmacist led DOAC class was associated with a 2.5-fold increase in persistence on rivaroxaban.

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes.

Although tetracyclines are an important class of antibiotics for use in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored, despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes that have a high potential for broad dissemination. Here, we show that tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a new tetracycline and tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics.

Physical Health Disparities Across Dimensions of Sexual Orientation, Race/Ethnicity, and Sex: Evidence for Increased Risk Among Bisexual Adults.

Accumulating evidence suggests that sexual minority individuals are at increased risk for physical health conditions compared to heterosexual individuals. However, we know little about physical health disparities affecting bisexual individuals, a population at increased risk for psychiatric and substance use conditions compared to both heterosexual and lesbian/gay populations. Using a large, nationally representative sample, we examined physical health disparities for bisexual individuals. To advance research on sexual minority health disparities, we further: (1) compared prevalence rates of physical health conditions across three dimensions of sexual orientation (i.e., identity, attractions, behavior) and (2) examined whether disparities differed by sex and race/ethnicity. Results indicated that sexual minority individuals were at increased risk for many physical health conditions. Notably, individuals with bisexual identity, attractions, and/or behavior were at increased risk for more physical health conditions than other sexual minority groups. The number and types of physical health disparities affecting bisexually identified individuals and individuals with same- and opposite-sex attractions and/or sexual partners varied across sex and race/ethnicity, with the most consistent disparities emerging for individuals who reported same- and opposite-sex sexual partners. Our findings highlight the substantial physical health disparities affecting sexual minorities and the heightened risk conferred by all facets of bisexuality.

Medical Reasons for Limiting Drinking: Data from a Sexual Health Clinic.

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.

Allosteric HIV-1 Integrase Inhibitors Lead to Premature Degradation of the Viral RNA Genome and Integrase in Target Cells.

Recent evidence indicates that inhibition of HIV-1 integrase (IN) binding to the viral RNA genome by allosteric integrase inhibitors (ALLINIs) or through mutations within IN yields aberrant particles in which the viral ribonucleoprotein complexes (vRNPs) are eccentrically localized outside the capsid lattice. These particles are noninfectious and are blocked at an early reverse transcription stage in target cells. However, the basis of this reverse transcription defect is unknown. Here, we show that the viral RNA genome and IN from ALLINI-treated virions are prematurely degraded in target cells, whereas reverse transcriptase remains active and stably associated with the capsid lattice. The aberrantly shaped cores in ALLINI-treated particles can efficiently saturate and be degraded by a restricting TRIM5 protein, indicating that they are still composed of capsid proteins arranged in a hexagonal lattice. Notably, the fates of viral core components follow a similar pattern in cells infected with eccentric particles generated by mutations within IN that inhibit its binding to the viral RNA genome. We propose that IN-RNA interactions allow packaging of both the viral RNA genome and IN within the protective capsid lattice to ensure subsequent reverse transcription and productive infection in target cells. Conversely, disruption of these interactions by ALLINIs or mutations in IN leads to premature degradation of both the viral RNA genome and IN, as well as the spatial separation of reverse transcriptase from the viral genome during early steps of infection.IMPORTANCE Recent evidence indicates that HIV-1 integrase (IN) plays a key role during particle maturation by binding to the viral RNA genome. Inhibition of IN-RNA interactions yields aberrant particles with the viral ribonucleoprotein complexes (vRNPs) eccentrically localized outside the conical capsid lattice. Although these particles contain all of the components necessary for reverse transcription, they are blocked at an early reverse transcription stage in target cells. To explain the basis of this defect, we tracked the fates of multiple viral components in infected cells. Here, we show that the viral RNA genome and IN in eccentric particles are prematurely degraded, whereas reverse transcriptase remains active and stably associated within the capsid lattice. We propose that IN-RNA interactions ensure the packaging of both vRNPs and IN within the protective capsid cores to facilitate subsequent reverse transcription and productive infection in target cells.

A Cross-Sectional Study of Depressive Symptoms and Risky Alcohol Use Behaviors Among HIV Primary Care Patients in New York City.

An association between problem drinking and depression among HIV-infected individuals has been previously demonstrated; however, which specific risky drinking behaviors are associated with higher levels of depression has not yet been investigated. Using an adult sample of HIV-infected primary care patients (78% male, 94% Black or Hispanic), we investigated whether depressive symptoms are associated with various risky drinking behaviors. Participants were administered the Beck Depression Inventory-II to assess depressive symptoms, and the Alcohol Use Disorders and Associated Disabilities Interview Schedule-IV to evaluate alcohol involvement. Participants with depressive symptoms (26%) were at higher risk for alcohol dependence [adjusted odds ratio (AOR) 3.8; 95% CI 2.0-7.2], regular binge drinking (AOR 2.0; 95% CI 1.1-3.8), and regular daytime drinking (AOR 2.1; 95% CI 1.2-3.8), in comparison with their non-depressed counterparts. Because both depression and unhealthy drinking negatively affect medication adherence and clinical outcomes, a better understanding of the association between depression and certain risky drinking behaviors among HIV-infected individuals is vital to improving their care and prognoses.

Heavy drinking among individuals with HIV: who drinks despite knowledge of the risk?

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.

Psychosocial Factors Associated with Problem Drinking Among Substance Users with Poorly Controlled HIV Infection.

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.