Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat.

With effective antiretroviral therapy (ART), many HIV-infected people die of diseases other than acquired immune deficiency syndrome (AIDS). In particular, coronary artery disease has emerged as one of most critical complications of HIV infection and a major cause of morbidity and mortality. Although reportedly antiretroviral combination therapy itself may accelerate atherosclerosis by enhancing dyslipidemia, most recent epidemiological studies support the notion that HIV infection itself contributes to cardiovascular disease. However, it is still a mystery how the virus can contribute to cardiovascular disease development even while suppressed by ARTs. This review discusses the current understanding of interactions between HIV infection and cardiovascular diseases in both clinical and experimental studies with special focus on those viral proteins that are still produced by HIV. This will help infectious disease/vascular biology experts to gain insights into the pathophysiological mechanisms of HIV-associated cardiovascular disease and new trends to treat and prevent cardiovascular disease in the HIV-infected population.

Pentoxifylline reduces tumor necrosis factor-α and HIV-induced vascular endothelial activation.

Untreated HIV infection is associated with endothelial dysfunction and subsequent cardiovascular disease, likely due to both direct effects of the virus and to indirect effects of systemic inflammation on the vasculature. We have recently shown that treatment with the antiinflammatory agent pentoxifylline (PTX) improved in vivo endothelial function and reduced circulating levels of the inflammatory markers vascular cell adhesion molecule-1 (VCAM-1) and interferon-gamma-induced protein (IP-10) in HIV-infected patients. To delineate the mechanisms underlying this therapeutic effect, we tested whether clinically relevant concentrations of PTX suppress VCAM-1 or IP-10 release in cultivated human lung microvascular endothelial cells. Indeed, we found that tumor necrosis factor (TNF)-α-induced VCAM-1 was reduced with concentrations of PTX in the low nanomolar range, comparable to plasma levels in PTX-treated groups. We also investigated the effect of HIV proteins and found that HIV transactivator of transcription (HIV-Tat) and HIV-envelope-derived recombinant gp120 enhanced TNF-α-induced VCAM-1 gene expression in lung microvascular and coronary macrovascular endothelial cells, respectively. In addition, PTX and a NF-κB-specific inhibitor reduced this enhanced VCAM-1 gene induction in microvascular and macrovascular endothelial cells. These results provide novel insights in how the antiinflammatory agent PTX can directly reduce HIV-associated proinflammatory endothelial activation, which may underlie vascular dysfunction and coronary vascular diseases.

Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow-up study.

PURPOSE: To prospectively evaluate body image, sexuality, emotional reactions (anxiety, depression), and quality of life in a sample of women having increased risk for breast cancer before and 6 months and 1 year after bilateral prophylactic mastectomy (BPM), and to compare preoperative expectations of the operation with postoperative reactions concerning the impact on six areas of the women's lives. PATIENTS AND METHODS: A total of 90 of 98 consecutive women who underwent BPM during October 1997 to December 2005 were included. Data were collected by self-administered questionnaires (eg, Hospital Anxiety and Depression scale, Swedish Short Term-36 Health Survey, Body Image Scale, Sexual Activity Questionnaire) before the operation (n = 81), and 6 (n = 71) and 12 months (n = 65) after BPM. RESULTS: Anxiety decreased over time (P = .0004). No corresponding difference was found for depression. No differences in health-related quality of life over time were found, with one exception. A substantial proportion of the women reported problems with body image 1 year after BPM (eg, self consciousness, 48%; feeling less sexually attractive, 48%; and dissatisfaction with the scars, 44%). Sexual pleasure was rated lower 1-year post-BPM as compared with before operation (P = .005), but no differences over time in habit, discomfort, or activity were found. CONCLUSION: No negative effects on anxiety, depression, and quality of life were found. Anxiety and social activities improved. Negative impact on sexuality and body image was reported.