The Aging Skeleton: Differences Between HIV-Infected Patients and the Uninfected Aging Population

In the past 10?years, a great attention has been given to bone metabolism impairment in patients with human immunodeficiency virus (HIV) as a specific organ damage associated with long-term toxicities of antiretroviral therapy. More recently, this issue has been better contextualized in the setting of the overlapping epidemic between HIV and aging. The objective of this review is to describe the aging skeleton as a paradigm of the biological aging process affecting patients with HIV infection. An increased prevalence of osteoporosis and osteopenia has been reported in both men and women infected with HIV, but the mechanism and consequences of these changes are not fully understood. Cohort studies have reported controversial data regarding the increase in fracture rates affecting HIV-infected patients compared with controls. Major determinants of bone mineral density changes over time include antiretroviral therapy exposure, body mass index, and lifestyle. Low CD4 cell count has been associated with fracture risk, suggesting that chronic immune activation and persistent inflammation may play an important role in bone demineralization and fracture development. Whether these findings will apply particularly to older HIV-infected people, who experience a higher chronic inflammation burden and are at highest risk of fragility fractures, is unknown. Definitively, the care of patients with HIV is becoming more complex as patients grow older and confront unique challenges.     

Physical and Mental Health Functioning of Urban HIV-Infected and Uninfected Mothers with Problem Drinking

Problem drinking is of great concern for mothers, especially those who are HIV-infected. We compared background characteristics, co-occurring drug use, and physical and mental health functioning of urban HIV-infected and uninfected mothers with problem drinking who were raising adolescents. Mothers in both groups reported similarly high levels of lifetime and current alcohol and drug use and poor physical and mental health. Health outcomes for mothers with problem drinking do not appear to be exacerbated by HIV status. Implications for intervention efforts with mothers and their adolescent children are discussed.     

Alcohol-Related Diagnoses and All-Cause Hospitalization Among HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United States Veterans from 1997 to 2011

Individuals with HIV infection are living substantially longer on antiretroviral therapy, but hospitalization rates continue to be relatively high. We do not know how overall or diagnosis-specific hospitalization rates compare between HIV-infected and uninfected individuals or what conditions may drive hospitalization trends. Hospitalization rates among United States Veterans were calculated and stratified by HIV serostatus and principal diagnosis disease category. Because alcohol-related diagnoses (ARD) appeared to have a disproportional effect, we further stratified our calculations by ARD history. A multivariable Cox proportional hazards model was fitted to assess the relative risk of hospitalization controlling for demographic and other comorbidity variables. From 1997 to 2011, 46,428 HIV-infected and 93,997 uninfected patients were followed for 1,497,536 person-years. Overall hospitalization rates decreased among HIV-infected and uninfected patients. However, cardiovascular and renal insufficiency admissions increased for all groups while gastrointestinal and liver, endocrine, neurologic, and non-AIDS cancer admissions increased among those with an alcohol-related diagnosis. After multivariable adjustment, HIV-infected individuals with an ARD had the highest risk of hospitalization (hazard ratio 3.24, 95 % CI 3.00, 3.49) compared to those free of HIV infection and without an ARD. Still, HIV alone also conferred increased risk (HR 2.08, 95 % CI 2.04, 2.13). While decreasing overall, risk of all-cause hospitalization remains higher among HIV-infected than uninfected individuals and is strongly influenced by the presence of an ARD.     

The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality

Purpose

For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes—notably mortality—is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality.

Methods

Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality.

Results

Of 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic co-interventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51–0.75; P?<?0.001) or physical rehabilitative therapies (HR 0.81; 95% CI 0.67–0.98; P?=?0.03) had a decreased risk of all-cause mortality compared to patients not receiving these services, whereas patients prescribed benzodiazepines concurrent with opioids had a higher risk of mortality (HR 1.39; 95% CI 1.12–1.66; P?<?0.001). Among patients with a current substance use disorder (SUD), those receiving SUD treatment had a lower risk of mortality than untreated patients (HR 0.47; 95% CI 0.32–0.68; P?=?< 0.001). No association was found between all-cause mortality and primary care visits (HR 1.12; 95% CI 0.90–1.26; P?=?0.32) or urine drug testing (HR 0.96; 95% CI 0.78–1.17; P?=?0.67).

Conclusions

Providers should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines.

     

Immunoglobulin Preparations for HIV-Infected Patients

Patients with the acquired immunodeficiency syndrome (AIDS) suffer from a deficiency of cellular immunity. However, some HIV-infected children and adults suffer from recurrent upper respiratory tract infections suggestive of a failure to synthesise specific antibodies, despite the hypergammaglobulinaemia that is present. Intravenous immunoglobulin (IV IgG) appears to benefit HIV-infected children with recurrent infections, in doses similar to those used for treating patients with primary hypogammaglobulinaemia. In some HIV-infected adults, IV IgG also appears to reduce bacterial respiratory infections but the treatment schedules remain to be defined. In patients with life-threatening bleeding due to immune thrombocytopenic purpura associated with HIV infection, high dose IV IgG treatment (1-2 g/kg) also increases platelet counts but unlike other therapies for ITP, is not immunosuppressive and has no other serious adverse effects. It is likely that over the next few years, specific anti-HIV preparations will be evaluated. Neutralising antibody has been demonstrated in HIV-infected patients and a specific antibody preparation against HIV might either prevent HIV infection after initial exposure to the virus or slow the progression of HIV-related disease. However, the development of a specific, effective, neutralising anti-HIV immunoglobulin preparation (whether polyclonal or monoclonal) will require information about which HIV antigens elicit protective immunity and the role played by neutralising antibody in HIV-related disease.     

Substance Use Predictors of Poor Medication Adherence: The Role of Substance Use Coping Among HIV-Infected Patients in Opioid Dependence Treatment

Many HIV-infected injection drug users (IDUs) continue to use illicit substances despite being in substance use treatment. Substance use is associated with non-adherence to HIV medications; however underlying mechanisms regarding this relation are understudied. The current investigation examined the role of substance use coping in terms of the relation between substance use and HIV medication adherence. Participants were 121 HIV-infected IDUs (41 % female, M age = 47, SD = 7.1) in opioid dependence treatment. Participants completed self-report questionnaires, were administered clinical interviews and oral toxicology screens, and used a medication-event-monitoring-system cap to assess 2 week HIV medication adherence. The use of cocaine and multiple substances were significantly related to decreased medication adherence. Substance use coping mediated these associations. Findings highlight the importance of assessing, monitoring, and targeting ongoing substance use, and ways to increase positive coping for HIV-infected IDUs in substance use treatment to aid in HIV medication adherence.     

Patient Activation and Improved Outcomes in HIV-Infected Patients

BACKGROUND

The Patient Activation Measure (PAM) assesses several important concepts in chronic care management, including self-efficacy for positive health behaviors. In HIV-infected populations, better self-efficacy for medication management is associated with improved adherence to antiretroviral medications (ARVs), which is critically important for controlling symptoms and slowing disease progression.

OBJECTIVE

To determine 1) characteristics associated with patient activation and 2) associations between patient activation and outcomes in HIV-infected patients.

DESIGN

Cross-sectional survey.

PARTICIPANTS

433 patients receiving care in four HIV clinics.

METHODS

An interviewer conducted face-to-face interviews with patients following their HIV clinic visit. Survey data were supplemented with medical record abstraction to obtain most recent CD4 counts, HIV viral load and antiretroviral medications.

MAIN MEASURES

Patient activation was measured using the 13-item PAM (possible range 0–100). Outcomes included CD4 cell count?>?200 cells/mL³, HIV-1 RNA?<?400 copies/mL (viral suppression), and patient-reported adherence.

KEY RESULTS

Overall, patient activation was high (mean PAM?=?72.3 [SD 16.5, range 34.7–100]). Activation was lower among those without vs. with a high school degree (68.0 vs. 74.0, p?<?.001), and greater depression (77.6 lowest, 70.2 middle, 68.1 highest tertile, p?<?.001). There was no association between patient activation and age, race, gender, problematic alcohol use, illicit drug use, or social status. In multivariable models, every 5-point increase in PAM was associated with greater odds of CD4 count?>?200 cells/mL³ (aOR 1.10 [95 % CI 1.01, 1.21]), adherence (aOR 1.18 [95 % CI 1.09, 1.29]) and viral suppression (aOR 1.08 [95 % CI 1.00, 1.17]). The association between PAM and viral suppression was mediated through adherence.

CONCULSIONS

Higher patient activation was associated with more favorable HIV outcomes. Interventions to improve patient activation should be developed and tested for their ability to improve HIV outcomes.     

HAART-Prolonged Life of HIV-Infected Patients Should Not Be Shortened by Hepatitis C

As highly active antiretroviral treatment (HAART) prolongs the life of HIV-infected individuals and reduces mortality associated with opportunistic infections, liver diseases have become a major challenge in the management of these patients. Up to 45% of deaths of persons with HIV are related to endstage liver disease, some of which might have been avoided with a less hesitant approach to hepatitis C treatment in the setting of HIV/ hepatitis C (HCV) coinfection.     

Prevalence and Genotypic Variability of TTV in HIV-Infected Patients

TT virus is a small, circular DNA virus, that has been associated with transfusion hepatitis. We sought to determine the prevalence of TT virus (TTV) in patients with human immunodeficiency virus (HIV) infection and to characterize the virus in terms of genotypic variability and in the relationship to CD4⁺, HIV viral loads, HCV/HIV coinfection, and ALT abnormalities. A cross-sectional analysis of HIV-infected patients in the United States, including 86 HIV-positive subjects and 118 HIV-negative controls was performed. TTV was detected using a seminested PCR technique. Samples underwent cloning and sequence analysis and/or RFLP to determine genotype. Thirty-eight percent of HIV-positive patients had TTV infection versus 14.4% of patients within the matching cohort (P = 0.0009). The highest rate of TTV infection was in patients with concurrent HCV/HIV infection (54% vs 30%, P = 0.038). HIV-infected subjects with TTV had lower ALT levels than those without TTV (P = 0.036). Intravenous drug use was the leading factor associated with TTV positivity among HIV-positive subjects. Mixed genotypes were more common in those with HIV. Therefore, TTV prevalence, ALT levels, and genomic heterogeneity of TTV all seem to be altered in patients with HIV.     

Outcomes of HIV-Infected Patients Receiving Care at Multiple Clinics

Receiving care at multiple clinics may compromise the therapeutic patient-provider alliance and adversely affect the treatment of people living with HIV. We evaluated 12,759 HIV-infected adults in Philadelphia, PA between 2008 and 2010 to determine the effects of using multiple clinics for primary HIV care. Using generalized estimating equations with logistic regression, we examined the relationship between receiving care at multiple clinics (≥1 visit to two or more clinics during a calendar year) and two outcomes: (1) use of ART and (2) HIV viral load ≤200 copies/mL for patients on ART. Overall, 986 patients (8 %) received care at multiple clinics. The likelihood of attending multiple clinics was greater for younger patients, women, blacks, persons with public insurance, and for individuals in their first year of care. Adjusting for sociodemographic factors, patients receiving care at multiple clinics were less likely to use ART (AOR = 0.62, 95 % CI 0.55–0.71) and achieve HIV viral suppression (AOR = 0.78, 95 % CI 0.66–0.94) than individuals using one clinic. Qualitative data are needed to understand the reasons for visiting multiple clinics.     

Prediction Model for Two-Year Risk of Opioid Overdose Among Patients Prescribed Chronic Opioid Therapy

Background

Naloxone is a life-saving opioid antagonist. Chronic pain guidelines recommend that physicians co-prescribe naloxone to patients at high risk for opioid overdose. However, clinical tools to efficiently identify patients who could benefit from naloxone are lacking.

Objective

To develop and validate an overdose predictive model which could be used in primary care settings to assess the need for naloxone.

Design

Retrospective cohort.

Setting

Derivation site was an integrated health system in Colorado; validation site was a safety-net health system in Colorado.

Participants

We developed a predictive model in a cohort of 42,828 patients taking chronic opioid therapy and externally validated the model in 10,708 patients.

Main Measures

Potential predictors and outcomes (nonfatal pharmaceutical and heroin overdoses) were extracted from electronic health records. Fatal overdose outcomes were identified from state vital records. To match the approximate shelf-life of naloxone, we used Cox proportional hazards regression to model the 2-year risk of overdose. Calibration and discrimination were assessed.

Key Results

A five-variable predictive model showed good calibration and discrimination (bootstrap-corrected c-statistic?=?0.73, 95% confidence interval [CI] 0.69–0.78) in the derivation site, with sensitivity of 66.1% and specificity of 66.6%. In the validation site, the model showed good discrimination (c-statistic?=?0.75, 95% CI 0.70–0.80) and less than ideal calibration, with sensitivity and specificity of 82.2% and 49.5%, respectively.

Conclusions

Among patients on chronic opioid therapy, the predictive model identified 66–82% of all subsequent opioid overdoses. This model is an efficient screening tool to identify patients who could benefit from naloxone to prevent overdose deaths. Population differences across the two sites limited calibration in the validation site.