Publications

BACKGROUND

Alcohol abuse has been associated with HIV/AIDS progression, but the effects of HIV infection and treatment on alcohol exposure have not been explored to date. This pilot study examines the relationship of untreated HIV infection to blood alcohol concentrations (BAC) relative to BAC after initiation of antiretroviral therapy (ART).

METHODS

Fifteen volunteers with untreated HIV/AIDS participated in 2 sets of alcohol or alcohol placebo administration studies before and after initiation of ART. Oral alcohol (1 g/kg) or alcohol placebo was administered, participants were followed for pharmacokinetics, subjective responses, and cognitive effects over 8 hours. After initial alcohol studies, the ART regimen selected by participant clinicians was instituted. Observed ART dosing took place for at least 2 weeks. Participants then returned for a second set of alcohol/placebo administration studies while on ART.

RESULTS

Participants had significantly higher BAC (P < 0.001) before ART than after ART administration. Alcohol area under the curve was significantly higher in untreated HIV disease (P = 0.011) with significantly higher C(max) (P = 0.015) and C(min) (P = 0.05). The elimination rate was not different between pre-ART and post-ART conditions. Despite declines in BAC after ART initiation, no differences in subjective responses were observed with alcohol administration.

CONCLUSIONS

Untreated HIV infection is associated with risk for higher BAC than that observed after ART. These findings indicate that patients with untreated HIV disease who ingest alcohol are at greater risk for alcohol associated adverse events and toxicities and underscores the need for simultaneous treatment of alcohol use disorders and HIV in patients with co-occurring conditions.

In most adult humans, hepatitis B is a self-limiting disease leading to life-long protective immunity, which is the consequence of a robust adaptive immune response occurring weeks after hepatitis B virus (HBV) infection. Notably, HBV-specific T cells can be detected shortly after infection, but the mechanisms underlying this early immune priming and its consequences for subsequent control of viral replication are poorly understood. Using primary human and mouse hepatocytes and mouse models of transgenic and adenoviral HBV expression, we show that HBV-expressing hepatocytes produce endoplasmic reticulum (ER)-associated endogenous antigenic lipids including lysophospholipids that are generated by HBV-induced secretory phospholipases and that lead to activation of natural killer T (NKT) cells. The absence of NKT cells or CD1d or a defect in ER-associated transfer of lipids onto CD1d results in diminished HBV-specific T and B cell responses and delayed viral control in mice. NKT cells may therefore contribute to control of HBV infection through sensing of HBV-induced modified self-lipids.

For the first time in the thirty-year history of AIDS, scientific research and successful HIV programs have made an AIDS-free generation a realistic global ambition. The President's Emergency Plan for AIDS Relief (PEPFAR) laid the foundation for reaching this goal. This article reviews PEPFAR's efforts to date and highlights programs, such as those encouraging voluntary male circumcision, that have worked to reduce HIV transmission and improve health for people with HIV. It also identifies remaining challenges, such as continuing to lower the costs of programs per unit of service delivered. PEPFAR will continue to expand and share its understanding of what works, focus on evidence-based "combination prevention" strategies, and make investments that maximize the impact of each dollar spent. It will also support growing ownership by partner countries of HIV/AIDS programs in terms of both management and financing, which are keys to the long-term sustainability of those programs. The article closes with a call to marshal every scientific, public health, and political tool at our disposal to achieve an AIDS-free generation.

Amid the global economic crisis, the President's Emergency Plan for AIDS Relief (PEPFAR) and other organizations have been pressed to do more with constrained resources to meet unmet needs in the worldwide HIV/AIDS pandemic. PEPFAR has approached this challenge through the development of an Impact and Efficiency Acceleration Plan, which includes improving the collection and use of economic and financial data, increasing the efficiency of HIV/AIDS program implementation, and collaborating with governments and multilateral organizations to maximize the impact of the resources provided by the United States. For example, by linking financial data with program outputs, PEPFAR was able to help its implementing partners in Mozambique reduce mean unit expenditures for people receiving antiretroviral treatment by 45 percent, from $265 to $145 per person, between 2009 and 2011. This article describes the plan's elements, provides examples of progress and challenges to its implementation, and assesses the prospects for further improvements in efficiency and impact.

In 2011 interim results of HIV Prevention Trials Network study 052, a National Institutes of Health study designed to test the effectiveness of antiretroviral treatment against the spread of HIV, were reported. These results showed that in a stable relationship in which one member of the couple was infected with HIV, treatment of the infected partner with antiretroviral drugs, combined with couples counseling and condom use, resulted in a 96 percent reduction in sexual transmission of HIV-1. This finding led to the use of antiretroviral treatment as a cornerstone of HIV prevention. Independent advisory committees of the President's Emergency Plan for AIDS Relief (PEPFAR) and the World Health Organization (WHO) have since issued analyses that set the stage for broader use of antiretroviral agents in treatment and prevention. This article describes the separate PEPFAR and WHO recommendations and outlines the design of prospective new trials to test how best to maximize the benefits of early treatment for prevention.

Acute lung injury is a common disorder with a high mortality rate, but previous efforts to develop drugs to treat this disorder have been unsuccessful. In an effort to develop more effective treatments, we have been studying the molecular pathways that regulate the dysfunction of alveolar epithelial cells and endothelial cells that serve as a final common pathway leading to alveolar flooding. Using integrin subunit knockout mice and antibodies we developed by immunizing these mice, we have found important and distinct roles for the αvβ6 integrin on epithelial cells and the αvβ5 integrin on endothelial cells in mediating increases in alveolar permeability in multiple models of acute lung injury. We have also found therapeutic effects of αvβ5 inhibition in two models of septic shock even when the antibody was administered to animals that were obviously ill. These results identify αvβ6 and αvβ5 as promising therapeutic targets for the treatment of acute lung injury and septic shock.

BACKGROUND

As cancer care shifts from hospital to outpatient settings, the number of cancer caregivers continues to grow. However, little is known about the cancer caregiving experience. This gap in knowledge is especially evident for racially diverse caregivers.

OBJECTIVE

This study, part of a multisite study of care recipients with either lung or colorectal cancer and their caregivers, examined the caregiving experiences of African American (AA) and white caregivers.

METHODS

Caregivers were identified by cancer patients in the Cancer Care Outcomes Research and Surveillance consortium. Caregivers completed a self-administered, mailed questionnaire that assessed their characteristics and experiences. Analysis of covariance was used to compare racial groups by objective burden and caregiving resources while controlling for covariates.

RESULTS

Despite greater preparedness for the caregiving role (P = .006), AA caregivers reported more weekly hours caregiving than whites did (26.5 ± 3.1 vs 18.0 ± 1.7; P = .01). In later phases of caregiving, AAs reported having more social support (P = .02), spending more hours caregiving (31.9 ± 3.5 vs 16.9 ± 1.9; P < .001), and performing more instrumental activities of daily living on behalf of their care recipient (P = .021).

CONCLUSION

Racial differences in the caregiving experience exist.

IMPLICATIONS FOR PRACTICE

Nurses play a key role in educating cancer patients and their caregivers on how to effectively cope with and manage cancer. Because AA caregivers seem to spend more time in the caregiving role and perform more caregiving tasks, AA caregivers may benefit from interventions tailored to their specific caregiving experience.

OBJECTIVE

Item 9 of the Patient Health Questionnaire-9 (PHQ-9), which inquires about both passive thoughts of death and active ideas of self-harm, has been used to assess suicide risk. The objectives of this study were (1) to determine the proportion of patients who responded "yes" to Item 9 who endorsed active suicidal ideation in response to more direct questions from a structured clinical interview and (2) to compare the sensitivity and specificity for detecting cases of depression of the PHQ-9 and the PHQ-8, which does not include Item 9, as well as the correlation between the PHQ-8 and PHQ-9.

METHODS

Coronary artery disease (CAD) outpatients were administered the PHQ-9 and the Computerized Diagnostic Interview Schedule (C-DIS). Item 9 responses were compared to suicidal ideation and intent in the last year based on the C-DIS. Scores on the PHQ-8 were obtained by eliminating Item 9 from the PHQ-9. Test characteristics of the PHQ-9 and PHQ-8 were compared.

RESULTS

Of 1022 patients, 110 (10.8%) endorsed Item 9. Of those, only 22 (19.8%) reported thoughts about committing suicide, and only 9 of those (8.1%) reported a suicide plan any time in the last year based on the C-DIS. Correlation between PHQ-9 and PHQ-8 scores was r=0.997. Sensitivity and specificity for the PHQ-9 (54%, 90%) and PHQ-8 (50%, 91%) to detect major depression were similar.

CONCLUSION

Item 9 does not appear to be an accurate suicide screen. The PHQ-8 may be a better option than the PHQ-9 in CAD patients.