Christine Wanke

Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study

Background:Cardiovascular disease (CVD) is an increasing cause of morbidity and mortality in HIV-infected patients. However, it is controversial whether HIV infection contributes to accelerated atherosclerosis independent of traditional CVD risk factors. Methods:Cross-sectional study of HIV-infected participants and controls without pre-existing CVD from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) and the Multi-Ethnic Study of Atherosclerosis (MESA). Preclinical atherosclerosis was assessed by carotid intima-medial thickness (cIMT) measurements in the internal/bulb and common regions in HIV-infected participants and controls after adjusting for traditional CVD risk factors. Results:For internal carotid, mean IMT was 1.17 ± 0.50 mm for HIV-infected participants and 1.06 ± 0.58 mm for controls (P < 0.0001). After multivariable adjustment for demographic characteristics, the mean difference of HIV-infected participants vs. controls was 0.188 mm [95% confidence interval (CI) 0.113–0.263, P < 0.0001]. Further adjustment for traditional CVD risk factors modestly attenuated the HIV association (0.148 mm, 95% CI 0.072–0.224, P = 0.0001). For the common carotid, HIV infection was independently associated with greater IMT (0.033 mm, 95% CI 0.010–0.056, P = 0.005). The association of HIV infection with IMT was similar to that of smoking, which was also associated with greater IMT (internal 0.173 mm, common 0.020 mm). Conclusion:Even after adjustment for traditional CVD risk factors, HIV infection was accompanied by more extensive atherosclerosis measured by IMT. The stronger association of HIV infection with IMT in the internal/bulb region compared with the common carotid may explain previous discrepancies in the literature. The association of HIV infection with IMT was similar to that of traditional CVD risk factors, such as smoking.

Weight Loss and Wasting Remain Common Complications in Individuals Infected with Human Immunodeficiency Virus in the Era of Highly Active Antiretroviral Therapy

It has been postulated that the use of highly active antiretroviral therapy (HAART) would reduce the occurrence of human immunodeficiency virus (HIV)-associated weight loss and wasting. To test this assumption, we evaluated, by means of longitudinal analysis, a prospective cohort of 469 HIV-infected individuals enrolled in a study of the impact of HIV on nutrition. Overall, 156 individuals in the cohort (33.5%) met at least 1 of these definitions of wasting. Furthermore, 58% of the cohort (289 patients) lost >1.5 kg of weight in a 6-month period between any 2 study visits. More than 50% of the cohort was receiving HAART at the time that they met 1 of the definitions of wasting; with regard to the occurrence of wasting; no differences were related to therapy.

Nutrition and HIV Infection: Review of Weight Loss and Wasting in the Era of Highly Active Antiretroviral Therapy from the Nutrition for Healthy Living Cohort

Despite major advances in the treatment and survival of patients infected with human immunodeficiency virus (HIV), weight loss and wasting remain common problems. In the HIV-infected population, weight loss is associated with lower CD4+ cell counts and is an independent predictor of mortality. The etiology of weight loss and wasting is complex and multifactorial. We discuss, on the basis of a large longitudinal cohort that examined nutritional status in HIV infection, data on weight loss and wasting from the present clinical era. The definition, prevalence, and significance of HIV-associated weight loss and wasting are summarized. The etiology of weight loss is discussed for 2 main categories: inadequate nutrient intake and altered metabolism. Finally, studies of interventions to treat HIV-associated weight loss and wasting are discussed. This information is intended to raise awareness among health care providers of HIV-infected patients that weight loss and wasting remain important acquired immunodeficiency syndrome-defining conditions, despite the advent of HAART.

Recombinant human growth hormone improves the fat redistribution syndrome (lipodystrophy) in patients with HIV.

OBJECTIVE To determine the efficacy of recombinant human growth hormone (rhGH) in the treatment of the fat redistribution syndrome (FRS) in patients with HIV. DESIGN A prospective, open-label study. SETTING An urban, university-affiliated Infectious Disease Clinic. PATIENTS Ten HIV-infected patients (seven men, three women) with FRS. INTERVENTIONS Treatment with 6 mg of rhGH a day, subcutaneously for 12 weeks. MAIN OUTCOME MEASURES Body mass index (BMI), body composition by bioelectrical impedance analysis (BIA), body composition by anthropometrics (including waist/hip ratio), buffalo hump. RESULTS The mean age was 41.7 years, the CD4 cell count was 247, and the HIV RNA was 95 735 copies/ml; 50% had undetectable viral RNA. The BMI was significantly increased from baseline to the end of treatment with growth hormone (25.3-26.9 kg/m2; P < 0.04); the waist/hip ratio significantly decreased from baseline levels, after treatment with growth hormone (1.03-0.9; P < 0.04); mid-thigh circumference increased significantly when baseline was compared with measures after treatment (49.1-51.8 cm; P < 0.03). One patient had to discontinue therapy because of hyperglycemia. CONCLUSION Short-term treatment with rhGH improved the alterations in body shape that occur with FRS in HIV-infected patients. Waist/hip ratios and mid-thigh circumference are useful measures to follow alterations in body shape in FRS.

Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence relative to the US population (National Health and Nutrition Examination Survey).

Background:Metabolic syndrome increases the risk of cardiovascular outcomes and type II diabetes. Most of the metabolic abnormalities defining metabolic syndrome are observed in HIV. Objective:To determine the incidence and risk factors for metabolic syndrome in HIV-infected adults in the Nutrition for Healthy Living (NFHL) study (2000-2003) and prevalence relative to the findings of the National Health and Nutrition Examination Survey (NHANES) (1999-2002). Methods:Metabolic syndrome is ≥3 of the following: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hypertension, abdominal obesity, and high serum glucose. The baseline prevalence of metabolic syndrome in the NFHL study (n = 477) was compared to that in the NHANES (n = 1876), adjusted for age, race, gender, poverty, exercise, and diet. Results:Almost one quarter of NFHL subjects had metabolic syndrome. Most with metabolic syndrome (77%) had low HDL and hypertriglyceridemia plus ≥1 additional abnormality. The prevalence of metabolic syndrome was significantly lower in HAART and non-HAART users compared with NHANES participants unadjusted for body mass index (BMI). After adjustment for BMI, it was no longer significant but the trend remained. The incidence of metabolic syndrome in the NFHL study was higher with increasing viral load, higher BMI, higher trunk-to-limb fat ratio, and Kaletra (lopinavir/ritonavir) or didanosine (ddI) use and lower among college-educated persons. Conclusions:Metabolic syndrome is mostly diagnosed through low HDL and high triglycerides in HIV. The risk of developing the syndrome is related to HIV, specific medications, and body fat.

Current Concepts in the Diagnosis and Management of Metabolic Complications of HIV Infection and Its Therapy

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.

Intestinal Microbiota, Microbial Translocation, and Systemic Inflammation in Chronic HIV Infection

BACKGROUND Despite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation. METHODS We profiled the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA) and measured markers of microbial translocation and systemic inflammation in 21 patients who had chronic HIV infection and were receiving suppressive ART (cases) and 16 HIV-uninfected controls. RESULTS The fecal microbial community composition was significantly different between cases and controls. The relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in cases, compared with controls. There were significant positive correlations between the relative abundances of Enterobacteriales and Enterobacteriaceae and the sCD14 level; the relative abundances of Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae and the interleukin 1β (IL-1β) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon γ level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-α level. There were negative correlations between endotoxin core IgM and IL-1β levels. CONCLUSIONS Patients who have chronic HIV infection and are receiving suppressive ART display intestinal dysbiosis associated with increased microbial translocation and significant associations between specific taxa and markers of microbial translocation and systemic inflammation. This was an exploratory study, the findings of which need to be confirmed.

Prevalence of, Evolution of, and Risk Factors for Fat Atrophy and Fat Deposition in a Cohort of HIV-Infected Men and Women

BACKGROUND At present, no uniform definition of human immunodeficiency virus (HIV)-associated lipoatrophy exists. The risk factors for fat atrophy (FA) and central fat deposition (FD) are multifactorial. We assessed the evolution and predictors of FA and FD in HIV-infected men and women. METHODS Participants (n = 452) were evaluated at baseline (starting in November 1998) and 1 year later. FA was defined as triceps skin-fold measurement less than the 10th percentile on the National Health and Nutrition Examination Survey for sex and age. FD was defined as a waist-to-hip ratio of > 0.95 for men and of > 0.85 for women. Predictors of the baseline prevalence of FA and FD and new cases of each syndrome after 1 year were determined. RESULTS The baseline prevalences of FA, FD, and combined FA and FD were 35%, 44%, and 14%, respectively. Twenty-two percent of subjects had newly developed FA at 1 year, and 16% of subjects with FA at baseline did not have it at 1 year. Also, 23% of subjects had newly developed FD at 1 year, and 15% of those with FD at baseline did not have it at 1 year. The risk of developing new FA was increased among participants with low triceps skin-fold values (P < .001), smaller hips (P < .001), higher nadir HIV load (P = .006), abacavir use (P < .001), stavudine use (P < .001), and use of highly active antiretroviral therapy (P = .002). The risk of developing new FD was higher among women (P < .001) and among participants with greater body fat levels (P = .005) and higher triglyceride levels (P < .001), and it was lower among those with a high school education (P = .003) and higher triceps skin-fold values (P = .026). CONCLUSIONS FA and FD are common in HIV-infected patients, but may change over time in the individual. FA and FD appear to be different syndromes, because risk factors for the development differ, and the prevalence of the combined syndrome differs from the prevalences of the 2 independent syndromes.

Cytomegalovirus Vasculitis: Case Reports and Review of the Literature

Cytomegalovirus (CMV) infection is a substantial cause of morbidity and mortality among immunocompromised patients. It may present with a mild, self-limited syndrome, retinitis, colitis, or invasive disease with pneumonitis, hepatitis, and bone marrow suppression. We review another, less common manifestation of CMV disease: CMV-associated vasculitis. CMV may productively infect vascular endothelial cells (25), causing a local vasculitis (3, 14, 19) and ischemia. Alternatively, the host immune response to cells expressing viral antigen may be the stimulus for vasculitis (12, 53). Since there are no pathognomonic appearances to mucosal or cutaneous lesions, biopsy of accessible sites is critical for diagnosis and expeditious initiation of appropriate antiviral therapy. The CMV-associated vasculitides represent a broad spectrum of diseases, with GI vasculitis in nontransplant recipients having the best prognosis. Cutaneous vasculitis associated with CMV seems to be a more fulminant disease, with the majority of cases having a fatal outcome. These differences likely reflect the degree of viral burden and the state of immune competence. Additionally, since the virus itself is immunosuppressive, host defenses may be further compromised by the infection. Although a large collective experience assessing the impact of ganciclovir and foscarnet is not currently available, both the prompt initiation of antiviral treatment and a concurrent reduction in any immunosuppressive regimen, including steroids, should be undertaken since these therapeutic strategies have clearly improved outcome for other CMV syndromes (22, 34, 55). As the number of recipients rises and the HIV pandemic spreads we are likely to see an increase in the number of cases of vasculitis associated with CMV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of Cardiovascular Disease in a Cohort of HIV-Infected Adults: A Study Using Carotid Intima-Media Thickness and Coronary Artery Calcium Score

BACKGROUND There is concern that human immunodeficiency virus (HIV) infection and the use of highly active antiretroviral therapy lead to accelerated atherosclerosis and increased risk of cardiovascular disease. We measured 2 surrogate markers of subclinical atherosclerosis, carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) scores, in HIV-infected adults. METHODS A cross-sectional analysis of 242 men and 85 women with HIV infection was used. Carotid ultrasonography and coronary computed tomography were performed, and their associations with cardiovascular risk factors were examined. RESULTS Among men, the mean (+/- standard deviation [SD]) common c-IMT was 0.62+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.76+/-0.5 mm, and 136 patients (56.1%) had detectable CAC. Among women, the mean (+/-SD) common c-IMT was 0.59+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.66+/-0.4 mm, and 40 patients (47.1%) had detectable CAC. Neither the c-IMT nor the CAC score differed by antiretroviral therapy class or individual medications for either sex. For men, age and waist circumference independently predicted common c-IMT; age, systolic blood pressure, and high-sensitivity C-reactive protein level independently predicted internal c-IMT; and age, apolipoprotein B level, and high-sensitivity C-reactive protein level independently predicted CAC score. For women, age and body mass index independently predicted common c-IMT; age independently predicted internal c-IMT; and age and glucose level independently predicted CAC score. CONCLUSIONS Our participants had more abnormal surrogate markers than expected at a relatively young age, but those were not associated with use of highly active antiretroviral therapy or protease inhibitors. At present, the positive associations were primarily with traditional and novel cardiovascular risk factors. Some HIV-specific (not treatment-specific) factors were observed; they may become more evident with prolonged HIV infection and treatment.