Healthcare Utilization Among Persons with HIV and Unhealthy Alcohol Use in St. Petersburg, Russia.

Few studies have examined the association between healthcare utilization and heavy alcohol use in Russia among persons with HIV (PWH), a group with high healthcare needs. This study analyzed the association between unhealthy alcohol use (defined as AUDIT score ≥ 8) and healthcare utilization among PWH with heavy alcohol use and daily smoking in St. Petersburg, Russia. This secondary analysis used data from a randomized controlled trial addressing alcohol use. The primary outcome was seeing an infectionist for HIV care in the past year. Outcomes were measured at baseline, 6 months, and 12 months. We assessed the association between unhealthy alcohol use and healthcare utilization outcomes with a repeated measures logistic regression model, controlling for relevant covariates. Nearly all (96.0%) participants had unhealthy alcohol use at baseline, and 90.0% had seen an infectionist for HIV care in the past year. In adjusted analyses, unhealthy alcohol use was associated with a 36% decrease in seeing an infectionist for HIV care (aOR = 0.64, 95% CI 0.43-0.95). Participants reported low levels of emergency department visits and hospitalizations. Understanding how to engage this population in alcohol use disorder treatment and HIV care is an important next step for improving health outcomes for this population.

Alcohol Consumption and Bone Mineral Density in People with HIV and Substance Use Disorder: A Prospective Cohort Study.

BACKGROUND: People living with HIV (PLWH) commonly have low bone mineral density (BMD) (low bone mass and osteoporosis) and are at high risk for fractures. Fractures and low BMD are significant causes of morbidity and mortality, increasingly relevant as PLWH age. Alcohol use is common among PLWH and known to affect bone health. The association between alcohol use and changes in BMD among PLWH is not well understood. METHODS: We conducted a 3.5-year prospective cohort study of 250 PLWH with substance use disorder or ever injection drug use. Annual alcohol consumption was measured as a mean of grams per day of alcohol, mean number of heavy drinking days per month, mean number of days abstinent per month, and any heavy drinking, using the 30-day Timeline Followback method twice each year. The primary outcome was annual change in BMD measured each year by dual energy X-ray absorptiometry in grams per square centimeter (g/cm2 ) at the femoral neck. Additional dependent variables included annual change in total hip and lumbar spine BMD, >6% annual decrease in BMD at any site, and incident fractures in the past year. Regression models adjusted for relevant covariates. RESULTS: The median age of participants was 50 years. The median duration of HIV infection was 16.5 years and the mean time since antiretroviral therapy initiation was 12.3 years. At study entry, 67% of participants met criteria for low BMD (46% low bone mass, 21% osteoporosis). Median follow-up was 24 months. We found no significant associations between any measure of alcohol consumption and changes in BMD (g/cm2 ) at the femoral neck (adjusted ß for g/d of alcohol = -0.0032, p = 0.7487), total hip, or lumbar spine. There was no significant association between any measure of alcohol consumption and >6% annual decrease in BMD at any site, or incident fractures. CONCLUSIONS: In this sample of PLWH and substance use disorders or ever injection drug use, we detected no association between any of the alcohol measures used in the study and changes in BMD or incident fractures.

Polypharmacy and risk of falls and fractures for patients with HIV infection and substance dependence.

Although people with HIV infection (PLWH) are at higher risk of polypharmacy and substance use, there is limited knowledge about potential harms associated with polypharmacy such as falls and fractures in this population. The study objective was to determine whether polypharmacy, as measured by the number and type of medication, is associated with falls and fractures among PLWH and DSM-IV substance dependence in the past year or ever injection drug use (IDU). We identified the number of medications by electronic medical record review in the following categories: (i) systemically active, (ii) non-antiretroviral (non-ARV), (iii) sedating, (iv) non-sedating as well as any opioid medication and any non-opioid sedating medication. Outcomes were self-reported (1) fall/accident requiring medical attention and (2) fracture in the previous year. Separate logistic regression models were fitted for medications in each category and each outcome. Among 250 participants, the odds of a fall requiring medical attention were higher with each additional medication overall (odds ratio [OR] 1.12, 95% Confidence Interval [CI] = 1.05, 1.18), each additional non-ARV medication (OR 1.13, 95%CI = 1.06, 1.20), each additional sedating medication (OR 1.36, 95%CI = 1.14, 1.62), and a non-opioid sedating medication (OR 2.89, 95%CI = 1.06, 7.85) but not with an additional non-sedating medication or opioid medication. In receiver operating characteristic (ROC) curve analyses, optimal cutoffs for predicting falls were: ≥8 overall and ≥2 sedating medications. Odds ratios for fracture in the previous year were OR 1.05, 95%CI = 0.97, 1.13 for each additional medication overall and OR 1.11, 95%CI = 0.89, 1.38 for each additional sedating medication. In PLWH and substance dependence or ever IDU, a higher number of medications was associated with greater odds of having a fall requiring medical attention. The association appeared to be driven largely by sedating medications. Future studies should determine if reducing such polypharmacy, particularly sedating medications, lowers the risk of falls.

Use of an android phone application for automated text messages in international settings: A case study in an HIV clinical trial in St. Petersburg, Russia.

BACKGROUND/AIMS: Reproducible outcomes in clinical trials depend on adherence to study protocol. Short message service (also known as text message) reminders have been shown to improve clinical trial adherence in the United States and elsewhere. However, due to systematic differences in mobile data plans, languages, and technology, these systems are not easily translated to international settings. METHODS: To gauge technical capabilities for international projects, we developed SMSMessenger, an automated Android application that uses a US server to send medication reminders to participants in a clinical trial in St. Petersburg, Russia (Zinc for HIV disease among alcohol users-a randomized controlled trial in the Russia Alcohol Research Collaboration on HIV/AIDS cohort). The application is downloaded once onto an Android study phone. When it is time for the text message reminders to be sent, study personnel access the application on a local phone, which in turn accesses the existing clinical trial database hosted on a US web server. The application retrieves a list of participants with the following information: phone number, whether a message should be received at that time, and the appropriate text of the message. The application is capable of storing multiple outgoing messages. With a few clicks, text messages are sent to study participants who can reply directly to the message. Study staff can check the local phone for incoming messages. The SMSMessenger application uses an existing clinical trial database and is able to receive real-time updates. All communications between the application and server are encrypted, and phone numbers are stored in a secure database behind a firewall. No sensitive data are stored on the phone, as outgoing messages are sent through the application and not by messaging features on the phone itself. Messages are sent simultaneously to study participants, which reduces the burden on local study staff. Costs and setup are minimal. The only local requirements are an Android phone and data plan. CONCLUSION: The SMSMessenger technology could be modified to be applied anywhere in the world, in any language, script, or alphabet, and for many different purposes. The novel application of this existing low-cost technology can improve the usefulness of text messaging in advancing the goals of international clinical trials.

Postoperative Venous Thromboembolism in Patients Undergoing Abdominal Surgery for IBD: A Common but Rarely Addressed Problem.

BACKGROUND: Venous thromboembolism after abdominal surgery occurs in 2% to 3% of patients with Crohn's disease and ulcerative colitis. However, no evidence-based guidelines currently exist to guide postdischarge prophylactic anticoagulation. OBJECTIVE: We sought to determine the use of postoperative postdischarge venous thromboembolism chemical prophylaxis, 90-day venous thromboembolism rates, and factors associated with 90-day thromboembolic events in IBD patients following abdominal surgery. DESIGN: This was a retrospective evaluation of an administrative database. DATA SOURCE: Data were obtained from Optum Labs Data Warehouse, a large administrative database containing claims on privately insured and Medicare Advantage enrollees. PATIENTS: Seven thousand seventy-eight patients undergoing surgery for Crohn's disease or ulcerative colitis were included in the study. MAIN OUTCOME MEASURES: Primary outcomes were rates of postdischarge venous thromboembolism prophylaxis and 90-day rates of postdischarge thromboembolic events. In addition, patient clinical characteristics were identified to determine predictors of postdischarge venous thromboembolism. RESULTS: Postdischarge chemical prophylaxis was given to only 0.6% of patients in the study. Two hundred thirty-five patients (3.3%) developed a postdischarge thromboembolic complication. Postdischarge thromboembolism was more common in patients with ulcerative colitis than with Crohn's disease (5.8% vs 2.3%; p < 0.001). Increased rates of venous thromboembolism were seen in patients undergoing colectomy or proctectomy with simultaneous stoma creation compared with colectomy or proctectomy alone (5.8% vs 2.1%; p < 0.001). The strongest predictors of thromboembolic complications were stoma creation (adjusted OR, 1.95; 95% CI, 1.34-2.84), J-pouch reconstruction (adjusted OR, 2.66; 95% CI, 1.65-4.29), preoperative prednisone use (adjusted OR, 1.57; 95% CI, 1.19-2.08), and longer length of stay (adjusted OR, 1.89; 95% CI, 1.41-2.52). LIMITATIONS: This study is limited by its retrospective design. CONCLUSIONS: The use of postdischarge venous thromboembolism prophylaxis in this patient sample was infrequent. Development of evidence-based guidelines, particularly for high-risk patients, should be considered to improve the outcomes of IBD patients undergoing abdominal surgery.

Food Insecurity, HIV Disease Progression and Access to Care Among HIV-Infected Russians not on ART.

Food insecurity (FI) has been associated with HIV disease progression among people on antiretroviral therapy (ART), presumably a consequence of poor medication adherence. We assessed whether there is a longitudinal association between FI and two primary outcomes reflecting on HIV disease progression (i.e., CD4 count and time to ART initiation) among people not on ART. Analyses used linear mixed effects and Cox models controlling for confounders. In this cohort (n = 310) FI was common (53%). Most (71.3%) reported past month heavy alcohol use and 37.1% reported past month injection drug use. Only 50 participants initiated ART during the study and mean time to ART was 128 days (SD 120). There were no significant differences in CD4 cell count between the groups with mild/moderate FI or severe FI versus those with no FI [adjusted mean difference, mild/moderate insecurity versus no FI -32.5 (95% CI -94.3, 29.3); severe versus no FI -45.5 (95% CI -124.1, 33.0); global p = 0.42]. We found no significant association between FI and longer time to ART initiation (p = 0.36). Food security is a desirable goal for overall health and shown beneficial for those on ART, however it does not appear to be associated with HIV disease progression among those with high prevalence of substance use and not yet on ART.

Alcohol Use and Food Insecurity Among People Living with HIV in Mbarara, Uganda and St. Petersburg, Russia.

Food insecurity (FI) is a documented problem associated with adverse health outcomes among HIV-infected populations. Little is known about the relationship between alcohol use and FI. We assessed whether heavy alcohol use was associated with FI among HIV-infected, antiretroviral therapy (ART)-naïve cohorts in Uganda and Russia. Inverse probability of treatment weighted logistic regression models were used to evaluate the association using cross-sectional baseline data. FI was experienced by half of the Russia cohort (52 %) and by a large majority of the Uganda cohort (84 %). We did not detect an association between heavy alcohol use and FI in either cohort (Russia: AOR = 0.80, 95 % CI 0.46, 1.40; Uganda: AOR = 1.00, 95 % CI 0.57, 1.74) or based on the overall combined estimate (AOR = 0.89, 95 % CI 0.60, 1.33). Future studies should explore the determinants of FI in HIV-infected populations to inform strategies for its mitigation.

HIV-infected individuals who use alcohol and other drugs, and virologic suppression.

People living with HIV (PLWH) on antiretroviral therapy (ART) who use substances were examined to (a) describe those with virologic control and (b) determine which substance use-factors are associated with lack of virologic control. Participants were adult PLWH taking ART with either past 12-month DSM-IV substance dependence or past 30-day alcohol or illicit drug use. Substance use factors included number of DSM-IV alcohol or drug dependence criteria and past 30-day specific substance use. Associations with HIV viral load (HVL) (<200 vs. ≥200 copies/mL) were tested using logistic regression models. Multivariable analyses adjusted for age, sex, homelessness and anxiety or depression. Participants (n = 202) were median age 50 years, 66% male, 51% African American and 75% self-reported ≥90% past 30-day ART adherence. Though HVL suppression (HVL <200 copies/mL) was achieved in 78% (158/202), past 30-day substance use was common among this group: 77% cigarette use; 51% heavy alcohol use; 50% marijuana; 27% cocaine; 16% heroin; and 15% illicit prescription opioid use. After adjusting for covariates, specific substance use was not associated with a detectable HVL, however number of past 12-month DSM-IV drug dependence criteria was (adjusted odds ratio = 1.23 for each additional criterion, 95% CI: 1.04-1.46). Three-quarters of a substance-using cohort of PLWH receiving ART had virologic control and ≥90% ART adherence. Substance dependence criteria (particularly drug dependence), not specifically substance use, were associated with lack of virologic control. Optimal HIV outcomes can be achieved by individuals who use alcohol or drugs and addressing symptoms of substance dependence may improve HIV-related outcomes.

Effects of Heavy Drinking on T-Cell Phenotypes Consistent with Immunosenescence in Untreated HIV Infection.

BACKGROUND: The role of alcohol consumption in HIV-related adaptive immune dysfunction is debated. We hypothesized that heavy drinking would be associated with greater evidence of immunosenescence (i.e., aging-related decline of adaptive immune function) among antiretroviral therapy (ART)-naïve HIV-infected individuals. METHODS: Using data from the Russia ARCH cohort study, we conducted a cross-sectional analysis of ART-naïve HIV-infected individuals recruited between 2012 and 2014. INDEPENDENT VARIABLE: Heavy drinking defined as >4 standard drinks in a day (or >14 standard drinks per week) for men and >3 per day (or >7 per week) for women, respectively. DEPENDENT VARIABLES: Percentage of CD8+ and CD4+ T-cells with a phenotype consistent with immunosenescence (i.e., expressing CD28- CD57+, or memory [CD45RO+ CD45RA+] phenotype and not the naïve [CD45RO- CD45RA+] phenotype). STATISTICAL ANALYSIS: Multiple linear regression adjusted for confounders. RESULTS: Of 214 eligible participants, 61% were heavy drinkers. Mean age was 33 years and the cohort was predominantly male (72%). Hepatitis C prevalence was high (87%) and mean log10 HIV-1 RNA copies/ml was 4.6. We found no significant differences by drinking status in the percentage of immunosenescent, memory, or naïve CD8+ or CD4+ T-cells. CONCLUSIONS: In this cross-sectional analysis, heavy drinking in the setting of untreated HIV infection did not appear to be associated with alterations in T-cell phenotypes consistent with immunosenescence. To substantiate these findings, longitudinal studies should assess whether changes in alcohol consumption are associated with changes in these and other immunosenescent T-cell phenotypes.

Epidemiological and Clinical Observations of Gonococcal Infections in Women and Prevention Strategies.

Neisseria gonorrhoeae is rapidly developing antimicrobial resistance. There is an urgent need for an effective gonococcal vaccine. In this study we examined epidemiological and clinical factors associated with gonorrhea in a cohort of women exposed to men with gonococcal urethritis attending the National Center for STD Control clinic in Nanjing, China, to understand the natural history and the risk factors for gonorrhea in this vulnerable population. This analysis will help identify the best target populations for vaccination, which is essential information for the development of vaccine strategies. We observed that 75% of the women in our cohort yielded a N. gonorrhoeae positive culture (infected women) and reported multiple sexual exposures to their infected partner. Infected women were younger than exposed but uninfected women. Contrary to the general belief that gonorrhea is asymptomatic in most women, 68% of the infected women acknowledged symptoms during their STD clinic visit, and overt inflammatory responses were detected upon medical examination in 88% of subjects. Other sexually transmitted infections were detected in 85% of subjects. This study confirmed that N. gonorrhoeae infections are underdiagnosed in women and, consequentially, untreated. Thus, our analysis reinforces the need to establish strategies for gonococcal prevention through the determination of the target population for a gonococcal vaccine.

Antibody Response to Hepatitis B Virus Vaccine is Impaired in Patients With Inflammatory Bowel Disease on Infliximab Therapy.

Background: Studies have demonstrated an association between anti-TNF/immunomodulator agents used in inflammatory bowel disease (IBD) and impaired hepatitis B virus (HBV) vaccine immunogenicity, but little data exist on whether specific medication types affect protective HBsAb titers. Our aim was to analyze this association. Methods: This is a retrospective cohort study. Inclusion criteria: age ≥18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), previous HBV vaccination series and/or ≥1 positive HBsAb, and record of IBD therapy in 6 months before titer level. Patients were stratified based upon medication exposures: anti-TNF, immunomodulator, combination anti-TNF and immunomodulatory, and a reference arm. Titer levels following vaccination and specific medication types given in the 6 months before titer were recorded. Seroprotection was defined as HBsAb ≥10 IU/l and ≥100 IU/l. Results: The study cohort (N = 391) was 70.8% white, 51.4% female and 64.2% had CD and 35.8% had UC. The mean age was 45.8 years. A significantly lower percentage of patients exposed to anti-TNF, immunomodulator or dual therapy had titers ≥10 (P < 0.01). Regarding specific medications, only patients exposed to infliximab (P < 0.01) were less likely to have titer levels ≥10, after controlling for other medication exposures, age at titer level, and interval time between vaccination/titer level. This was not found for patients exposed to adalimumab, methotrexate, 6-mercaptopurine, or azathioprine. Conclusions: Patients exposed to infliximab were significantly less likely to have protective HBsAb titer levels following vaccination, a trend not seen in patients on adalimumab. Efforts to vaccinate IBD patients against HBV before use of immunomodulators and anti-TNFs, infliximab specifically, and screen periodically thereafter must be reinforced.

Polypharmacy and risk of non-fatal overdose for patients with HIV infection and substance dependence.

INTRODUCTION: People living with HIV (PLWH) are at risk of both polypharmacy and unintentional overdose yet there are few data on whether polypharmacy increases risk of overdose. The study objective was to determine if the number and type of medication (e.g., sedating) were associated with non-fatal overdose (OD) among PLWH with past-year substance dependence or a lifetime history of injection drug use. MATERIALS AND METHODS: This was a longitudinal study of adults recruited from two urban, safety-net HIV clinics. Outcomes were i) lifetime and ii) past-year non-fatal OD assessed at baseline and a 12-month follow-up. We used logistic regression to examine the association between each outcome and the number of medications (identified from the electronic medical record) in the following categories: i) overall medications, ii) non-antiretroviral (non-ARV), iii) sedating, iv) non-sedating, as well as any vs no opioid medication and any vs no non-opioid sedating medication. Covariates included demographics, medical comorbidities, depressive and anxiety symptoms, and substance use. RESULTS: Among 250 participants, 80% were prescribed a sedating medication, 50% were prescribed an opioid; 51% exceeded risky drinking limits. In the past month, 23% reported illicit opioid use and 9% illicit opioid sedative use; 37% reported lifetime non-fatal OD and 7% past-year non-fatal OD. The median number (interquartile range) of total medications was 10 (7, 14) and 2 (1, 3) sedating. The odds of lifetime non-fatal OD were significantly higher with each additional sedating medication (OR 1.26, 95% CI 1.08, 1.46) and any opioid medication (OR 2.31; 95% CI 1.37, 3.90), but not with each overall, non-ARV, or non-sedating medication. The odds of past year non-fatal OD were greater with each additional sedating medication (OR 1.18; 95% CI 1.00, 1.39, p=0.049), each additional non-ARV medication (OR 1.07; 95% CI 1.00, 1.15, p=0.048), and non-significantly for any opioid medication (OR 2.23; 95% CI 0.93, 5.35). CONCLUSIONS: In this sample of PLWH with substance dependence and/or injection drug use, number of sedating medications and any opioid were associated with non-fatal overdose; sedating medications were prescribed to the majority of patients. Polypharmacy among PLWH and substance dependence warrants further research to determine whether reducing sedating medications, including opioids, lowers overdose risk.

Lifetime and recent alcohol use and bone mineral density in adults with HIV infection and substance dependence.

Low bone mineral density (BMD) is common in people living with HIV infection (PLWH), increasing fracture risk. Alcohol use is also common in PLWH and is a modifiable risk factor for both HIV disease progression and low BMD. In PLWH, alcohol's effect on BMD is not well understood.We studied adult PLWH with substance dependence. We measured lifetime alcohol use (kg) and recent (i.e., past 30-day) alcohol use (categorized as: abstinent, low risk, or high risk). In adjusted multivariable regression analyses, we tested associations between lifetime and recent alcohol use and (i) mean BMD (g/cm) at the femoral neck, total hip, and lumbar spine and (ii) low BMD diagnosis (i.e., osteopenia or osteoporosis). We also examined associations between 2 measures of past alcohol use (i.e., total consumption [kg] and drinking intensity [kg/year]) and BMD outcome measures during 3 periods of the HIV care continuum: (i) period before first positive HIV test, (ii) period from first positive HIV test to antiretroviral therapy (ART) initiation, and (iii) period following ART initiation.We found no significant associations between lifetime alcohol use and mean femoral neck (ß -0.000, P = .62), total hip (ß -0.000, P = .83) or lumbar spine (ß 0.001, P = .65) BMD (g/cm), or low BMD diagnosis (adjusted odds ratio [aOR] = 0.98, 95% Confidence Interval [CI]: 0.95-1.01). There was no significant correlation between past 30-day alcohol use and mean BMD (g/cm). Past 30-day alcohol use was associated with low BMD diagnosis (P = .04); compared to abstainers, the aOR for high risk alcohol use was 1.94 (95% CI: 0.91-4.12), the aOR for low risk alcohol use was 4.32 (95% CI: 1.30-14.33). Drinking intensity (kg/year) between first positive HIV test and ART initiation was associated with lower mean BMD (g/cm) at the femoral neck (ß -0.006, P = .04) and total hip (ß -0.007, P = .02) and increased odds of low BMD (aOR = 1.18, 95% CI = 1.03-1.36).In this sample of PLWH, we detected no association between lifetime alcohol use and BMD. However, recent drinking was associated with low BMD diagnosis, as was drinking intensity between first positive HIV test and ART initiation. Longitudinal studies should confirm these associations.