Sheila Medina

Nonalcoholic fatty liver disease among HIV-infected persons.

Objective:To describe the prevalence and factors associated with nonalcoholic fatty liver disease (NAFLD) among HIV-infected persons not infected with hepatitis C virus (HCV). Design:A cross-sectional study among HIV-infected patients in a large HIV clinic. Methods:NAFLD was defined as steatosis among patients without viral hepatitis (B or C) coinfection or excessive alcohol use. The prevalence of NAFLD was identified by ultrasound examination evaluated by 2 radiologists blinded to the clinic information; liver biopsies were performed on a subset of the study population. Factors associated with NAFLD were evaluated by proportional odds logistic regression models. Results:Sixty-seven of 216 patients (31%) had NAFLD based on ultrasound evaluation. Among those with NAFLD, steatosis was graded as mild in 60%, moderate in 28%, and severe/marked in 12%. Factors associated with the degree of steatosis on ultrasound examination in the multivariate model included increased waist circumference [odds ratio (OR) 2.1 per 10 cm, P < 0.001], elevated triglyceride levels (OR 1.2 per 100 mg/dL, P = 0.03), and lower high-density lipoprotein levels (OR 0.7, per 10 mg/dL, P = 0.03). African Americans were less likely to have NAFLD compared with whites (14% vs. 35%), although this did not reach statistical significance (OR 0.4, P = 0.08). Similar associations were noted for the subset of patients diagnosed by liver biopsy. CD4 cell count, HIV viral load, duration of HIV infection, and antiretroviral medications were not independent risk factors associated with NAFLD after adjustment for dyslipidemia or waist circumference. Conclusions:NAFLD was common among this cohort of HIV-infected HCV-seronegative patients. NAFLD was associated with a greater waist circumference, low high-density lipoprotein, and high triglyceride levels. Antiretroviral medications were not associated with NAFLD; prospective studies are needed to confirm this finding.

Obesity among Patients with HIV: The Latest Epidemic

Since the advent of highly active antiretroviral therapy (HAART), studies have been conflicting regarding weight information among patients with HIV. We performed a retrospective study among male patients with HIV between June 2004 and June 2005 at two large U.S. Navy HIV clinics to describe the prevalence and factors associated with being overweight/obese. Rates of obesity/overweight among HIV-positive patients were also compared to data from HIV-negative military personnel. Of the 661 HIV-infected patients, 419 (63%) were overweight/obese and only 5 (1%) were underweight. Patients with HIV had a mean age of 41.0 years (range, 20-73 years) and were racially diverse. The prevalence rates of being overweight/obese at the last visit were similar among both HIV-positive and -negative military members. Being overweight/obese at the last clinic visit was associated with gaining weight during the course of HIV infection (10.4 versus 4.0 pounds, p < 0.001), hypertension (36% versus 23%, p = 0.001), low high-density lipoprotein (HDL; 40% versus 31%, p < 0.001), and a higher CD4 cell count at last visit (592 versus 499 cells/mm(3), p < 0.001). These data demonstrate that patients with HIV in the HAART era are commonly overweight and/or obese with rates similar to the general population. Being overweight/obese is associated with hypertension and dyslipidemia. Weight assessment and management programs should be a part of routine HIV clinical care.

A randomized clinical trial comparing revaccination with pneumococcal conjugate vaccine to polysaccharide vaccine among HIV-infected adults

BACKGROUND The risk of pneumococcal disease persists, and antibody responses to revaccination with the 23-valent polysaccharide vaccine (PPV) are low among human immunodeficiency virus (HIV)-infected adults. We determined whether revaccination with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these responses. METHODS In a randomized clinical trial, we compared the immunogenicity of revaccination with PCV ( n = 131) or PPV (n = 73) among HIV-infected adults (median CD4 cell count, 533 cells/mm(3)) who had been vaccinated with PPV 3-8 years earlier. HIV-uninfected adults (n = 25) without prior pneumococcal vaccination received 1 dose of PCV. A positive response was defined as a >or=2-fold increase (from baseline to day 60) in capsule-specific immunoglobulin G, with a postvaccination level >or=1000 ng/mL for at least 2 of the 4 serotypes. RESULTS HIV-infected persons demonstrated a higher frequency of positive antibody responses to PCV than to PPV (57% vs 36%) (P = .004) and greater mean changes in the immunoglobulin G concentration from baseline to day 60 for serotypes 4, 9V, and 19F (P < .05, for all), but not for serotype 14. However, by day 180, both outcomes were similar. Responses to PCV were greater in frequency and magnitude for all serotypes in HIV-uninfected adults, compared with those in HIV-infected adults. CONCLUSIONS Among persons with HIV infection, revaccination with PCV was only transiently more immunogenic than PPV, and responses were inferior to those in HIV-uninfected subjects with primary vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity are needed for HIV-infected adults. Clinical trial registration. ClinicalTrials.gov identifier NCT00622843.

Prevalence and Factors Associated with Renal Dysfunction Among HIV-Infected Patients

Renal dysfunction is an increasingly recognized non-AIDS-defining comorbidity among HIV-infected persons. The role of HIV-related factors in renal dysfunction remains unclear. We performed a cross-sectional study at two military clinics with open access to care to determine the impact of HIV factors, including antiretroviral therapy, on renal function. Renal dysfunction was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m(2). We evaluated 717 HIV patients with a median age of 41 years; 92% were male, 49% Caucasian, and 38% African American; median CD4 count was 515 cells/mm(3) and 73% were receiving highly active antiretroviral therapy (HAART). Twenty-two patients (3%) had renal dysfunction. Factors associated with renal dysfunction in the multivariate logistic analyses included older age (odds ratio [OR] 2.0 per 10 year increase, p = 0.006), lower CD4 nadir (OR 0.6 per 100 cell change, p = 0.02), and duration of tenofovir use (OR 1.5 per year use, p = 0.01). Among persons initiating tenofovir (n = 241), 50% experienced a reduction in GFR (median -10.5 mL/min/1.73 m(2), 95% CI, -8.9 to -13.3) within 2 years. Among tenofovir users, factors associated with a reduction in GFR included female gender (p < 0.001), African American ethnicity (p = 0.003), and lower CD4 nadir (p = 0.002). In summary, renal dysfunction was relatively uncommon among our HIV-infected patients, perhaps due to their young age, lack of comorbidities, or as a result of our definition that did not include proteinuria. Renal dysfunction was associated with duration of tenofovir use. Factors associated with renal loss among tenofovir users included female gender, African American ethnicity, and CD4 nadir <200 cells/mm(3). Consideration for more frequent monitoring of kidney function among these select HIV patients may be warranted.

Prevalence and factors associated with liver test abnormalities among human immunodeficiency virus-infected persons.

BACKGROUND & AIMS Liver disease is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected persons. We evaluated the prevalence, etiology, and factors associated with liver dysfunction in patients during the highly active antiretroviral therapy era. METHODS We performed liver tests (baseline and after a 6-month follow-up period) in HIV-infected patients treated at a large clinic. Comprehensive laboratory and ultrasound analyses were performed. Factors associated with liver test abnormalities were assessed using multivariate logistic regression models. RESULTS Eighty of 299 HIV-positive patients (27%) had abnormal liver test results during the 6-month study period. The majority of abnormalities were grade 1. Of those with liver test abnormalities, the most common diagnosis was nonalcoholic fatty liver disease (30%), followed by excessive alcohol use (13%), chronic hepatitis B (9%), chronic active hepatitis C (5%), and other (hemochromatosis and autoimmune hepatitis, 2%); 8 participants (10%) had more than 1 diagnosis. In total, 39 HIV patients with abnormal liver test results (49%) had a defined underlying liver disease. Despite laboratory tests and ultrasound examination, 41 abnormal liver test results (51%) were unexplained. Multivariate analyses of this group found that increased total cholesterol levels (odds ratio, 1.6 per 40-mg/dL increase; P = .01) were associated with liver abnormalities. CONCLUSIONS Liver test abnormalities are common among HIV patients during the highly active antiretroviral therapy era. The most common diagnosis was nonalcoholic fatty liver disease. Despite laboratory and radiologic investigations into the cause of liver dysfunction, 51% were unexplained, but might be related to unrecognized fatty liver disease.

Fatty liver disease is associated with underlying cardiovascular disease in HIV‐infected persons*

Cardiovascular disease is an increasing concern among HIV‐infected persons and their providers. We determined if fatty liver disease is a marker for underlying coronary atherosclerosis among HIV‐infected persons.

Clinically significant incidental findings among human immunodeficiency virus-infected men during computed tomography for determination of coronary artery calcium.

Those infected with the human immunodeficiency virus (HIV) have a greater risk of cardiovascular disease and might undergo computed tomographic (CT) scans for early detection. Incidental findings on cardiac CT imaging are important components of the benefits and costs of testing. We determined the prevalence and factors associated with incidental findings on CT scans performed to screen for coronary artery calcium (CAC) among HIV-infected men. A clinically significant finding was defined as requiring additional workup or a medical referral. A total of 215 HIV-infected men were evaluated. Their median age was 43 years; 17% were current tobacco users; the median CD4 count was 580 cells/mm(3); and 83% were receiving antiretroviral medications. Also, 34% had a positive CAC score of >0. An incidental finding was noted among 93 participants (43%), with 36 (17%) having ≥1 clinically significant finding. A total of 139 findings were noted, most commonly pulmonary nodules, followed by granulomas, scarring, and hilar adenopathy. Most of the incidental findings were stable on follow-up, and no malignancies were detected. The factors associated with the presence of an incidental finding in the multivariate model included increasing age (odds ratio 1.6 per 10 years, p <0.01), positive CAC score (odds ratio 2.3, p <0.01), and current tobacco use (odds ratio 2.5, p = 0.02). In conclusion, incidental findings were common among HIV-infected men undergoing screening CT imaging for CAC determination. The incidental findings were more common among older patients and those with detectable CAC.

The association of ethnicity with antibody responses to pneumococcal vaccination among adults with HIV infection

Ethnicity may be associated with the incidence of pneumococcal infections and the frequency of protective vaccine responses. Earlier studies have suggested that HIV-infected persons of black ethnicity develop less robust immune responses to pneumococcal vaccination that may relate to their higher incidence of invasive disease. We evaluated the association of ethnicity with capsule-specific antibody responses to pneumococcal revaccination, with either the pneumococcal conjugate (PCV) or polysaccharide (PPV) vaccines among 188 HIV-infected adults. The proportion of the 77 African Americans (AA) and 111 Caucasians with comparable virologic and immunologic parameters who achieved a positive immune response (≥2-fold rise in capsule-specific IgG from baseline with post-vaccination value ≥1 μg/mL for ≥2 of 4 serotypes) at day 60 after revaccination was similar (43% vs. 49%, respectively, p=0.65). Results were also similar when vaccine types (PPV and PCV) were examined separately. Mean changes in log(10) transformed IgG levels from baseline to days 60 and 180 post-vaccination were also not significantly different between AA and Caucasians. In summary, in this ethnically diverse cohort with equal access to care, we did not observe differential antibody responses between AA and Caucasian HIV-infected adults after pneumococcal revaccination.

Adiponectin Levels and Coronary Artery Disease among HIV-Infected Men

Objective: HIV-infected persons frequently experience lipodystrophy and are at higher risk of cardiovascular disease, but the impact of adipose-related hormones, such as adiponectin, on Coronary Artery Disease (CAD) remains unclear. We evaluated the association of plasma adiponectin levels and the presence of CAD. Design: A cross-sectional study among HIV-infected men in a large HIV clinic. Methods: HIV-infected participants underwent CT scan imaging to determine CAD as measured by Coronary Artery Calcium (CAC) scores categorized as no detectable disease (0), minimum disease (1-100), and significant disease (>100). Factors associated with CAD, including adiponectin levels, were evaluated using multivariate logistic regression modeling. Results: 213 HIV-infected men were evaluated with a median age of 43 years, median CD4 count of 583 cells/ mm3, and 69% had HIV RNA 100 (p=0.09). Adiponectin levels were inversely correlated with lipohypertrophy, hypertension, and triglyceride levels (p<0.05), while FRS was marginally correlated (X2=3.1, p=0.08). In the final multivariate model, increasing age (OR 3.8 per 10 year increase, 95% CI 2.56-5.71, p<0.001) was significantly associated with CAC, and adiponectin approached significance (OR 0.8 per 1 μg/ml increase, 95% CI 0.69-1.00, p=0.05). Conclusions: Low adiponectin levels are common among HIV-infected persons. Adiponectin is correlated with lipohypertrophy and lower levels approached significance with CAD. Understanding the role of adiponectin in the pathogenesis of CAD may allow for targeted treatment and prevention strategies among HIV-infected persons.