James M. Sosman

Use of Human Immunodeficiency Virus-1 Protease Inhibitors Is Associated With Atherogenic Lipoprotein Changes and Endothelial Dysfunction

Background—Human immunodeficiency virus protease inhibitors (HIV PIs) are associated with hyperlipidemia, hyperglycemia, and obesity; however, it is not known whether they increase risk of atherosclerotic vascular disease. The purposes of this study were to characterize the lipoprotein abnormalities associated with use of HIV PIs in individuals with HIV infection and to determine the pathophysiological significance of these changes by assessing their effect on endothelial dysfunction. Methods and Results—This was a cross-sectional study of 37 adults with HIV-1 infection who were receiving antiretroviral therapy. Twenty-two were taking HIV PIs (group 1); 15 were not (group 2). Lipids and lipoproteins were measured by enzymatic techniques and nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was measured by high-resolution ultrasound. Subjects in both groups were similar in regard to age, time since diagnosis of HIV infection, and CD4 cell count. Group 1 subjects had higher total cholesterol (5.68 versus 4.42 mmol/L, P =0.007) and triglyceride (4.43 versus 1.98 mmol/L, P =0.009) levels, characterized by elevated levels of IDL and VLDL. Subjects in group 1 had impaired FMD (2.6±4.6%), indicative of significant endothelial dysfunction. Group 2 subjects had normal FMD (8.1±6.7%, P =0.005). In group 1, chylomicron, VLDL, IDL, and HDL cholesterol levels predicted FMD. Conclusions—Use of HIV PIs is associated with atherogenic lipoprotein changes and endothelial dysfunction. Because these metabolic and vascular changes predispose to atherosclerosis, monitoring and treatment of dyslipidemia in patients taking these medications is warranted.

Predictors of risky sex of young men after release from prison.

A longitudinal study of demographic and behavioural characteristics associated with risky sexual behaviours of young men after release from prison. One hundred and six men were interviewed in prison and at one week and six months after release. Overall, 37% reported a previous sexually transmitted disease (STD) diagnosis. In the 30 days before incarceration, 33% had had sex with a risky partner, and 59% had had multiple female sex partners. After release, 38 (36%) men reported having had risky sex (≥2 female sex partners and unprotected vaginal sex): 12 (13%) at one week and 31 (34%) at six months. The only factor independently associated with risky sex was the use of alcohol/drugs before sex: one-week odds ratio (OR)=6.11 (95% confidence interval [CI]: 1.42-26.40), six-month OR=3.05 (95% CI: 1.30-9.42). Behavioural intervention programmes for incarcerated men should address drug and alcohol use and its contribution to higher risk for HIV and STDs.

Unprotected sex with multiple partners: implications for HIV prevention among young men with a history of incarceration.

Objectives: The objectives of this study were to describe preincarceration risk behaviors of young men and identify correlates of unprotected sex with multiple partners during the 3 months before incarceration. Study: Data on preincarceration risk behaviors were obtained from 550 men, aged 18 to 29 years, in state prisons in California, Mississippi, Rhode Island, and Wisconsin. Correlates of unprotected sex with multiple partners were determined by logistic regression. Results: Of 550 participants, 71% had multiple sex partners, 65.1% had sex with a partner they perceived as risky, and 45.3% engaged in unprotected sex with multiple partners. Men who drank heavily (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.11–2.54) or who had a risky partner (OR, 3.90; 95% CI, 2.60–5.85) were more likely to report unprotected sex with multiple partners. Men who attended religious gatherings (OR, 0.66; 95% CI, 0.46–0.96) or lived in stable housing (OR, 0.69; 95% CI, 0.48–1.00) were less likely to report unprotected sex with multiple partners. Conclusions: Most participants engaged in behaviors that could result in a sexually transmitted disease, including HIV. Prevention programs should address the relationship between heavy alcohol use and risky sexual behavior. Discharge planning should address housing needs. Faith-based community organizations may play an important role for some young men in their transition to the community.

Isoproterenol inhibition of isolated human neutrophil function

The human PMN can contribute to the inflammatory response. Several neutrophil responses can be inhibited by agonists that increase the cellular levels of cyclic AMP. In the following article, we compared the effects of ISO on lysosomal beta-glucuronidase release, superoxide generation, and CL in isolated human PMNs. ISO inhibited the neutrophil CL response to opsonized zymosan in a dose-dependent fashion with maximal effects at 10(-4)M. ISO inhibition of CL was not enhanced by the addition of theophylline, nor was CL inhibited by the exogenous addition cyclic AMP except at a very high concentration of 10(-3)M. ISO also suppressed beta-glucuronidase release and superoxide generation in neutrophils during an incubation with opsonized zymosan particles. For ISO to inhibit beta-glucuronidase release and superoxide generation, theophylline (5 X 10(-4)M) was necessary. ISO effectively inhibits three neutrophil functions that are capable of causing tissue inflammation. Although ISO suppressed all three neutrophil responses, the inhibitory mechanisms appear to be variable.

Whole-body positron emission tomography in patients with HIV-1 infection.

Positron emission tomography with fluorine-18-deoxyglucose (FDG-PET) detects active lymphoid tissues during HIV-1 infection in man. We used FDG-PET to study anatomical correlates of HIV-1 infection in man. Whole-body FDG-PET images from 15 patients with HIV-1 showed distinct lymphoid tissue activation in the head and neck during acute disease, a generalised pattern of peripheral lymph-node activation at mid-stages, and involvement of abdominal lymph nodes during late disease. Unexpectedly, HIV-1 progression was evident by distinct anatomical correlates, suggesting that lymphoid tissues are engaged in a predictable sequence. Understanding the anatomy of HIV-1 infection could encourage use of surgical or radiological interventions to supplement chemotherapy.

Prevention Strategies for Cardiovascular Disease in HIV-Infected Patients

Effective antiretroviral therapy (ART) improves the survival of patients with human immunodeficiency virus (HIV) infection.1 With increased life expectancy, HIV-infected patients increasingly are experiencing complications of illnesses that are not directly related to HIV infection.2 Cardiovascular disease (CVD), the leading cause of death in the United States,3 recently has been recognized as an important cause of morbidity and mortality among patients with HIV (see Working Group 2, Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy).2,4–6 Among these patients, traditional CVD risk factors predict CVD events; however, certain components of ART appear to be associated with increased CVD risk.5 Much of the increased CVD risk observed in patients undergoing ART is related primarily to the effects of ART on traditional CVD risk factors; however, direct effects of ART on the vasculature and other inflammatory, immune, and viral factors associated with HIV infection may also contribute to increased CVD risk.5,7,8 A central tenet of preventing CVD is that the intensity of risk-reducing interventions should be based on the level of CVD risk.9 Patients with established CVD are at the highest risk and qualify for the most aggressive risk factor management, with special focus on interventions that have been proven to prevent cardiovascular death, myocardial infarction, and stroke. For patients without established CVD, management is based on the presence of risk factors for developing complications of CVD, such as death, myocardial infarction, and stroke9–12 (see Working Group 4, Screening and Assessment of Coronary Heart Disease in HIV-Infected Patients). The intensity of CVD risk-reducing therapy, however, must be modified by the context of the patient’s overall health. This is an especially important consideration in patients with HIV infection, who often have competing morbidities that may be as likely to …

Substance Use and Sexual Behavior during Incarceration among 18- to 29-Year Old Men: Prevalence and Correlates

An A-CASI survey of 197 men with a history of incarceration, ages 18–29, revealed that 50% and 17% of participants, respectively, had used substances or had sex while confined. Univariate regression analyses indicated that these two behaviors were correlated and both were associated with being older, having spent more years incarcerated, being sexual abused, and being involved with gangs and violence during incarceration. Multiple regression analyses showed that the likelihood of any substance use during incarceration was higher for men who were affiliated with a gang. Men were more likely to have had sex during incarceration if they reported having had a male sex partner in the community. The prevalence of sexual behavior also differed across sites. Findings document the occurrence of substance use and sexual behavior among incarcerated men, and highlight the need for continued research into the context of these behaviors.

Postprandial Lipoprotein Changes in Patients Taking Antiretroviral Therapy for HIV Infection

Objective— Dyslipidemia is common among patients receiving antiretroviral therapy for HIV infection. The purpose of this study was to determine whether postprandial lipemia contributes to the dyslipidemia observed in HIV-positive patients taking antiretroviral therapy. Methods and Results— A standardized fat load was administered to 65 subjects (group 1 35 HIV-positive subjects receiving protease inhibitors [PIs]; group 2 20 HIV-positive subjects not receiving PIs; group 3 10 HIV-negative controls). Serum triglycerides, retinyl palmitate, and lipoproteins were measured using enzymatic and nuclear magnetic resonance spectroscopic techniques. Compared with HIV-negative controls, peak postprandial retinyl palmitate and large very low-density lipoprotein (VLDL) levels occurred later in both HIV-positive groups, and a delayed decrease in serum triglycerides was observed. However, postprandial areas under the curve (AUCs) for triglycerides, retinyl palmitate, chylomicrons, and large VLDL were similar. Postprandial AUCs for intermediate-density lipoproteins (IDLs) and low-density lipoproteins (LDLs) were higher in group 1 than groups 2 and 3 (all P<0.035). Conclusions— Postprandial clearance of triglyceride-rich lipoproteins is delayed in HIV-positive individuals receiving antiretroviral therapy. Compared with HIV-positive individuals not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial IDLs and LDLs.

Screening for sexually transmitted diseases and hepatitis in 18-29-year-old men recently released from prison: feasibility and acceptability

Men entering prisons have high rates of sexually transmitted disease (STD), hepatitis, and HIV. This study sought to determine the acceptability and feasibility of screening for STD and hepatitis in young men released from prison. Participants were interviewed six months after release and offered free screening. Of 42 (56%) eligible men who participated in the qualitative interview, 33 (79%) provided at least a blood or urine specimen. Eight of 33 (24%) men tested had chlamydia, trichomoniasis, hepatitis B or C virus (HBV or HCV). Three of 32 (9%) had chlamydia, three of 32 (9%) had trichomoniasis, two of 28 (7%) had prior syphilis, and two of 28 (7%) had HCV. Of 28 tested for HBV, six (21%) were immune, two (7%) had chronic infection, and 20 (71%) were susceptible. Barriers to screening included lack of forewarning, inconvenience, and insufficient incentive. In conclusion, screening for STD and hepatitis among former inmates can be acceptable and feasible. Forewarning, reducing the time burden, and providing monetary incentives may increase screening rates.

Prerelease intent predicts smoking behavior postrelease following a prison smoking ban.

INTRODUCTION More than 2 million persons are incarcerated in the United States. Most are young minority men, soon to reenter the community. The majority are also lifelong smokers with high rates of health-related problems. As prisons implement smoking bans, it is not known whether health behavior change that is mandated, rather than selected, can be maintained. The Wisconsin Department of Corrections smoking ban is a unique opportunity to investigate determinants of smoking behavior after release from prison. METHODS A convenience sample of 49 incarcerated men near release participated in two interviews (1-month prerelease, in prison, and 1-month postrelease via telephone). Descriptive analyses and multivariate modeling were conducted to determine associations with postrelease smoking. RESULTS Participants had a mean age of 36.7 years, 12.4 years of education, and a 2.3-year incarceration; 47% were Black and 41% White. They had smoked 14.5 years. Most (67%) believed that their health was improved after the smoking ban. Paired t tests revealed decreases in Positive and Negative Affect Scale negative affect (p = .001) and Patient Health Questionnaire-8 depression (p = .009) postrelease. Univariate analysis showed correlations of intent to smoke upon release with smoking relapse postrelease (p = .001), White race with smoking relapse postrelease (p = .045), and perceived better health since the prison smoking ban with nonsmoking on release (p = .01). There was a trend toward use of alcohol with smoking relapse on release (p = .061). DISCUSSION Prerelease smoking intention predicted postrelease behavior. Belief in improved health after the prison smoking ban correlated with nonsmoking on release. Targeted relapse prevention interventions are needed for people reentering the community.