HIV-negative Subjects Research Articles

HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study.

BackgroundCardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear.Methods92 HIV− infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV−) subjects underwent 1H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals.ResultsRelative to HIV− individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (p<.04) and higher myo-inositol (mIo) (p<.04); in the caudate: lower NAA (p = .01); and in the posterior cingulate cortex: higher mIo (p<.008– also significant when Holm-Sidak corrected) and higher Choline/NAA (p<.04). Regression models showed that an HIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter.ConclusionsIn chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by chronic inflammation.

The effect of HIV infection on atherosclerosis and lipoprotein metabolism: A one year prospective study

ObjectivesHIV infection is associated with dyslipidaemia and increased risk of cardiovascular disease. The effects of HIV infection and antiretroviral treatment on surrogate markers of atherosclerosis, and lipoprotein metabolism were evaluated in a 12 month prospective study. Methods and resultsTreatment-naive HIV patients were recruited into one of three groups: untreated HIV infection not likely to require initiation of antiretroviral therapy (ART) for at least 12 months; initiating treatment with non nucleoside reverse transcriptase inhibitor-containing ART regimen and initiating treatment with protease inhibitor-containing ART regimen. The patients underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity (PWV), brachial flow-mediated dilation (FMD) and variables of plasma lipoprotein metabolism at baseline and 12 months. The findings were compared with published values for age and sex matched HIV-negative healthy subjects in a cross-sectional fashion. cIMT and FMD were lower while PWV was higher in HIV-patients compared with HIV-negative individuals; none of the markers changed significantly during 12 months follow up. HIV patients had hypoalphalipoproteinemia and elevated plasma levels of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein. The only significant changes in lipid-related variables were elevation of total cholesterol and triglycerides in patients treated with PI-containing regimen and elevation of plasma LCAT levels in patients treated with NNRTI-containing regimen. The ability of whole and apoB-depleted plasma to effect cholesterol efflux was not impaired in all three groups. ConclusionsThis study did not find evidence for rapid progression of subclinical atherosclerosis and deterioration of dyslipidaemia in HIV patients within 1 year.

Deficits in Self-Awareness Impact the Diagnosis of Asymptomatic Neurocognitive Impairment in HIV

A recent national survey of HIV(+) adults noted that nearly three-quarters of cognitively impaired individuals are categorized as having asymptomatic neurocognitive impairment (ANI), lacking documented compromise of everyday function. The clinical impact and long-term consequences of ANI are unknown and the importance of this asymptomatic diagnosis has raised concerns in clinical care settings where competing priorities often exist. In this study, we conducted structured tests of everyday functioning in a sample of HIV(+) subjects over 60 years of age and asked subjects to rate their performance relative to peers. We demonstrate that individuals with neuropsychological testing impairment often lack self-awareness of functional performance deficits. Specifically, ANI subjects rated functional performance similar to that of HIV-negative control subjects, despite noted deficits in objective measures of function. These findings have important implications for use of self-report of function in the diagnosis of HIV-associated neurocognitive disorders (HAND), likely underestimating symptomatic impairment.

High prevalence and incidence of human papillomavirus in a cohort of healthy young African female subjects

ObjectivesWe measured the prevalence and incidence of human papillomavirus (HPV) infection in young female subjects recruited for a safety and immunogenicity trial of the bivalent HPV-16/18 vaccine in Tanzania.MethodsHealthy HIV...

Revised Central Nervous System Neuropenetration-Effectiveness Score is Associated with Cognitive Disorders in HIV-Infected Patients with Controlled Plasma Viraemia

The objective of our study was to compare two different central nervous system penetration-effectiveness (CPE) scores for the prediction of cognitive dysfunction in HIV-infected patients. We performed a cross-sectional single cohort study, consecutively enrolled during routine outpatient visits. HIV-infected subjects on antiretroviral therapy with plasma HIV RNA<50 copies/ml were included. A neuropsychological battery was administered. Each patient was classified as cognitively impaired on the basis of results obtained in age-, gender-, education- and nationality-matched healthy HIV-negative subjects. Self-reported adherence to antiviral therapy was measured on a 0-100 visual analogue scale. CPE rank was calculated for each antiretroviral regimen based on rules proposed by the CHARTER group in the 2008 original version (orCPE rank) and the 2010 revised version (revCPE rank). Neuroeffectiveness categories were analysed based on cutoffs of ≥1.5 (orCPE rank) or ≥6 (revCPE rank). A total of 101 patients were enrolled (66% male, median age 47 years, median education 13 years); mean adherence was 81%. orCPE rank ≥1.5 and revCPE rank ≥6 were observed in 85.0% and 78.2% of patients, respectively (P=0.31). Asymptomatic neurocognitive impairment (ANI) was diagnosed in 50 (49.5%) subjects. In a multivariable model, after adjusting for nationality, adherence and nadir CD4(+) T-cell count, orCPE rank did not show an association with cognitive performance (P=0.704). By contrast, patients with revCPE rank ≥6 (OR 0.32, 95% CI 0.11, 0.95; P=0.039) and adherence ≥80% (OR 0.39, 95% CI 0.15, 0.99; P=0.047) showed a decreased risk of cognitive impairment. A high prevalence of ANI was observed in virologically suppressed HIV-infected individuals. The revCPE rank showed improved association with neurocognitive dysfunction over the orCPE rank. Moreover, a relationship between cognitive impairment and adherence to antiretroviral therapy was found.

Long-Term Suppressive Combined Antiretroviral Treatment Does Not Normalize the Serum Level of Soluble CD14

Levels of soluble CD14 (sCD14) were longitudinally measured in 85 human immunodeficiency virus (HIV)-infected subjects during long-term receipt of suppressive combined antiretroviral therapy (cART) and compared to those in young and elderly HIV-negative control subjects. cART did not normalize sCD14 levels; rather, the HIV-infected group displayed a significantly higher sCD14 level at baseline (ie, before cART initiation), 1 year after cART initiation, and 5 years after cART initiation, compared with both control groups. Furthermore, the baseline CD4(+) T-cell count was inversely associated with the baseline sCD14 level. Our results point to the necessity of complementary therapies to treat the activated/inflamed status associated with chronic HIV infection and to the benefits of early initiation of cART.

Hepatitis C virus and human immunodeficiency virus coinfection among attendants of voluntary counseling and testing centre and HIV follow up clinics in Mekelle Hospital.

IntroductionHepatitis C virus remains a large health care burden to the world. HIV and HCV coinfection is major global health concern worldwide. However, there is limited information on the prevalence of HCV/HIV co-infection in Ethiopia. The aim of the study was to assess the magnitude of HIV/HCV coinfection and the potential risk factors in attendants of voluntary counseling and testing centre and HIV follow up clinics of Mekelle hospital.MethodsA cross sectional seroprevalence survey of HCV infection was carried out on 300 HIV negative and positive subjects attending voluntary counseling and testing (VCT) center and HIV follow up clinics of Mekelle hospital, Ethiopia from December 2010-February 2011. Serum samples were tested for anti-HCV antibodies using immunochromatographic test.ResultsOf the 300 study participants, 126(42%) were HIV negative and 174(58%) HIV seropositive from VCT and HIV follow up clinics, respectively. The overall anti-HCV prevalence was 18(6.0%). There were no significant differences in HCV seroprevalence among the different categories of age and sex (p> 0.05). Of the 174 persons with HIV, 16 (9.2%) cases had antibodies to HCV, where as among 126 HIV negative subjects 2 (1.58%) were HCV seropositive (p= 0.006, OR= 6.28, 95% CI= 1.42-27.82).ConclusionAccordingly, there was a significant difference in sero-positivity of HCV between HIV positive and HIV negative participants. No apparent risk factor that caused HCV infection was inferred from this study.

Cerebrospinal fluid abnormalities in HIV-negative patients with secondary and early latent syphilis and serum VDRL ≥ 1:32

Background:Syphilis is caused by a spirochete Treponema pallidum. Invasion of the central nervous system (CNS) by T. pallidum may appear early during the course of disease. The diagnosis of confirmed neurosyphilis is based on the reactive Venereal Disease Research Laboratory (VDRL) in cerebrospinal fluid (CSF). Recent studies indicated that serum RPR ≥ 1:32 are associated with higher risk of reactivity of CSF VDRL.Aims:The main aim of the current study was to assess cerebrospinal fluid serological and biochemical abnormalities in HIV negative subjects with secondary and early latent syphilis and serum VDRL ≥ 1:32.Materials and Methods:Clinical and laboratory data of 33 HIV-negative patients with secondary and early latent syphilis, with the serum VDRL titer ≥ 1:32, who underwent a lumbar puncture and were treated in Department of Dermatology at Jagiellonian University School of Medicine in Cracow, were collected.Results:Clinical examination revealed no symptoms of CNS involvement in all patients. 18% (n = 6) of patients met the criteria of confirmed neurosyphilis (reactive CSF-VDRL). In 14 (42%) patients CSF WBC count ≥ 5/ul was found, and in 13 (39%) subjects there was elevated CSF protein concentration (≥ 45 mg/dL). 10 patients had CSF WBC count ≥ 5/ul and/or elevated CSF protein concentration (≥ 45 mg/dL) but CSF-VDRL was not reactive.Conclusions:Indications for CSF examination in HIV-negative patients with early syphilis are the subject of discussion. It seems that all patients with syphilis and with CSF abnormalities (reactive serological tests, elevated CSF WBC count, elevated protein concentration) should be treated according to protocols for neurosyphilis. But there is a need for identification of biomarkes in order to identify a group of patients with syphilis, in whom risk of such abnormalities is high.

Organ Damage in HIV-Positive Patients with High Blood Pressure

Our objective has been the investigation of possible cardiovascular or renal organ damage in HIV patients with confirmed high blood pressure by means of instrumental cardiovascular investigation and renal function evaluation. A total of 265 consecutive patients accessing our outpatient facility were enrolled in the study. Patients with confirmed pathological pressure values or high normal values were submitted to clinical and instrumental monitoring by 24-hour ambulatory blood pressure monitoring (ABPM), to derivation of 12-lead ECG registration, to echocardiography and to epi-aortic vessel echo-color-Doppler. The ECG and echocardiographic data were compared to a control group of 40 hypertensive HIV-negative subjects. Renal damage was evaluated by means of the microalbuminuria/creatininuria ratio on a spot urine sample, plus 24-hour albuminuria and proteinuria measurements. 61 (23.0%) of the subjects examined were hypertensive: 24 (39.3%) had a previous hypertensive diagnosis but had never been treated for this condition, and 37 (60.7%) had a new diagnosis; In 100% of cases, 24-hour ABPM confirmed the hypertension and 27.8% of the patients resulted non-dippers. The ECG showed left ventricle overload, V4-V6 strain, or left ventricular hypertrophy in 64.3% of cases compared to 35.7% in the control group. Echocardiography demonstrated increasing in left ventricle parietal thickness with concentric remodeling and hypertrophy in 85.2% of patients. HIV-positive patients showed a statistically significant tendency to concentric remodeling and concentric hypertrophy, even in presence of mild hypertension. Echocolor-Doppler examination detected intima-media thickness > and/or carotid plaques in 72.1% of patients. Renal function seems spared in these subjects. Our data highlights the importance of investigating arterial hypertension among our patients as it is a frequently undiagnosed condition, and illustrates the utility of 24- hr ABPM to confirm hypertension and to identify the non-dipper subject. Moreover, the ECG, echocardiography and echocolor-Doppler examinations evidenced a premature tendency to organ damage in these patients that showed altered cardiac remodeling compared to those without HIV. This stresses the need for an early diagnosis, including a complete instrumental evaluation to properly identify organ damage even at a subclinical level.

The Expression of Cholesterol Metabolism Genes in Monocytes From HIV-Infected Subjects Suggests Intracellular Cholesterol Accumulation

Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P < .01), with HDL-c inversely correlated with HIV RNA (ρ = -0.52; P < .01). Expression of genes involved in cholesterol uptake (LDLR, CD36), synthesis (HMGCR), and regulation (SREBP2, LXRA) was significantly lower in both ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

Differences between HIV‐infected and uninfected adults in the contributions of smoking, diabetes and hypertension to acute coronary syndrome: two parallel case–control studies

The aim of the study was to assess the separate contributions of smoking, diabetes and hypertension to acute coronary syndrome (ACS) in HIV-infected adults relative to uninfected adults. Two parallel case-control studies were carried out. In the first study, HIV-positive adults diagnosed with ACS between 1997 and 2009 (HIV+/ACS) were matched for age, gender and known duration of HIV infection with HIV-positive adults without ACS (HIV+/noACS), each individual in the HIV+/ACS group being matched with three individuals in the HIV+/noACS group. In the second study, each individual in the HIV+/ACS group in the first study was matched for age, gender and calendar date of ACS diagnosis with three HIV-negative individuals diagnosed with ACS between 1997 and 2009 (HIV-/ACS). Each individual in the HIV-/ACS group was then matched for age and gender with an HIV-negative adult without ACS (HIV-/noACS). After matching, the ratio of numbers of individuals in the HIV+/ACS, HIV+/noACS, HIV-/ACS and HIV-/noACS groups was therefore 1 : 3 : 3 : 3, respectively. We performed logistic regression analyses to identify risk factors for ACS in each case-control study and calculated population attributable risks (PARs) for smoking, diabetes and hypertension in HIV-positive and HIV-negative individuals. There were 57 subjects in the HIV+/ACS group, 173 in the HIV+/noACS group, 168 in the HIV-/ACS group, and 171 in the HIV-/noACS group. Independent risk factors for ACS were smoking [odds ratio (OR) 4.091; 95% confidence interval (CI) 2.086-8.438; P < 0.0001] and a family history of cardiovascular disease (OR 7.676; 95% CI 1.976-32.168; P = 0.0003) in HIV-positive subjects, and smoking (OR 4.310; 95% CI 2.425-7.853; P < 0.0001), diabetes (OR 5.778; 95% CI 2.393-15.422; P = 0.0002) and hypertension (OR 6.589; 95% CI 3.554-12.700; P < 0.0001) in HIV-negative subjects. PARs for smoking, diabetes and hypertension were 54.35 and 30.58, 6.57 and 17.24, and 9.07 and 38.81% in HIV-positive and HIV-negative individuals, respectively. The contribution of smoking to ACS in HIV-positive adults was generally greater than the contributions of diabetes and hypertension, and was almost twice as high as that in HIV-negative adults. Development of effective smoking cessation strategies should be prioritized to prevent cardiovascular disease in HIV-positive adults.

Influence of age and CD4+ T cell counts on the prevalence of genital human papillomavirus infection among HIV‐seropositive men who have sex with men in Taiwan

This study aimed to examine the baseline prevalence of genital human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-seropositive men who have sex with men in Taiwan and to determine the association of age and CD4+ T cell counts with HPV infection. In 2010, 305 men who have sex with men infected with HIV and 100 HIV-seronegative men who have sex with men were recruited. Genital swabs were collected and 37 HPV genotypes were detected using linear array HPV genotyping. HPV infection was present in 45.3% of the patients infected with HIV and in 18% of the HIV-negative subjects (P < 0.001). HPV types 52, 51, and 16 were the most commonly identified oncogenic types. Oncogenic HPV types were identified in 31.2% of the patients infected with HIV and in 13% of the seronegative subjects (P < 0.001). Adjusted odd ratios (ORs) for the detection of any HPV type were 2.9 (95% confidence interval [CI], 1.4-5.9) for men who have sex with men aged 30-34 and 2.1 (95% CI, 1.1-4.3) for those aged >35 compared with that for those aged <25. ORs were 2.8 (95% CI, 1.0-7.4) for a CD4+ T cell count of 200-350 cells/µl and 8.5 (95% CI, 2.9-24.5) for a CD4+ T cell count of <200 cells/µl compared with that for seronegative subjects. In conclusion, this novel HPV study, carried out in Northern Taiwan on men who have sex with men, revealed that age and immune state were associated significantly and independently with HPV infection.

Myasthenia gravis developing in an HIV-negative patient with Kaposi’s sarcoma

Myasthenia gravis is a disorder of neuromuscular transmission caused by autoimmune mechanisms. We reported a possible association between seropositive myasthenia gravis and Kaposi's sarcoma in a HIV-negative subject and the observed interactions between the treatment regimen for these two conditions. A 62-year-old man came to our attention for ocular myasthenia gravis. He suffered from a classic form of Kaposi's sarcoma since about 1 year. When myasthenic symptoms worsened, the patient was started on prednisone and azathioprine. The patient had a significant worsening of Kaposi's sarcoma, so prednisone and azathioprine were reduced and he was treated with vinblastine, with improvement both in dermatologic than in neurological symptomatology. We propose some considerations: the potential correlation between Kaposi's sarcoma and myasthenia gravis through immunological mechanism; myasthenia gravis as a paraneoplastic manifestation of Kaposi's sarcoma, and the role of an antitumoral agent as a treatment for both the conditions.

Hodgkin Lymphoma in Patients with HIV Infection: A Review

Hodgkin lymphoma (HL) is one of the most common types of non-AIDS-defining tumors in the HIV-infected. Its incidence however seems to have increased under highly active anti-retroviral therapy (HAART). HIV-HL is a different entity from HL in HIV-negative subjects with a poorer prognosis that is associated with tumor-subtype, EBV-infection, and "B" symptoms. Despite the aggressive nature of the disease, clinical outcome has improved with combination therapies including appropriately timed antiretroviral strategies and the quality of supportive care-notably the use of hematopoietic growth factors. More intensive chemotherapy regimens with or without autologous stem cell transplantation appear to improve survival. Functional imaging such as positron emission tomography and computed tomography (FDG-PET) may help guide treatment strategy and minimize long-term toxicity.

Risk of Spontaneous Intracranial Hemorrhage in HIV-infected Individuals: A Population-based Cohort Study

We studied the association between HIV infection, antiretroviral medications, and the risk of spontaneous intracranial hemorrhage. We performed a cohort and nested case control study in an administrative database. We selected all HIV-positive individuals presenting between 1985 and 2007. Each HIV-positive subject was matched with 4 HIV-negative individuals. We used a Poisson regression model to calculate rates of intracranial hemorrhage according to HIV status. We conducted a case -control study nested within the cohort of HIV-positive individuals to look at the effect of antiretroviral medications. Odds ratios for antiretroviral exposure were obtained using conditional logistic regression. There were 7,053 HIV-positive and 27,681 HIV-negative subjects, representing 138,704 person-years. There were 49 incident intracranial hemorrhages, 29 in HIV-positive and 20 in HIV-negative individuals. The adjusted hazard ratio for intracranial hemorrhage in HIV-positive compared to HIV-negative patients was 3.28 (95% confidence interval [CI] 1.75-6.12). The effect was reduced to 1.99 (95% CI 0.92-4.31) in the absence of AIDS-defining conditions, and increased to 7.64 (95% CI 3.78-15.43) in subjects with AIDS-defining conditions. Hepatitis C infection, illicit drug or alcohol abuse, intracranial lesions, and coagulopathy were all strongly associated with intracranial hemorrhage (all P < .001). In the case control study, 29 cases of ICH in HIV-positive individuals were matched to 228 HIV-positive controls. None of the antiretroviral classes were associated with an increase in the odds ratio of intracranial hemorrhage. The risk of intracranial hemorrhage in HIV-positive individuals seems to be mostly associated with AIDS-defining conditions, other comorbidities, or lifestyle factors. No association was found between use of antiretroviral medications and intracranial hemorrhage.

Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects

TUTI-16 is a synthetic universal HIV-1 Tat epitope vaccine, designed to induce anti-Tat antibodies that block the function of circulating Tat, an HIV encoded protein secreted by HIV-1 infected cells. Circulating Tat activates CD4 T cells, permitting HIV replication and sustained viremia. Safety, immunogenicity and antiretroviral potential of TUTI-16 were explored in a randomized double-blind dose-escalating study in asymptomatic treatment-naïve HIV-1 infected subjects. TUTI-16 was safe, with mild local and systemic injection-related adverse reactions, but the antibody response was barely detectable. Surprisingly, a highly statistically significant reduction of HIV-1 viral load was found in the lowest 30 μg vaccine dose group (p < 0.01) but not at the higher doses. We posited that an anti-Tat antibody response below the limit of detection inhibited HIV viral load at this dose, an effect nullified at higher vaccine doses by activating cytokines induced by adjuvant components in TUTI-16. To clarify this immunogenicity/activation conundrum open label immunogenicity studies were performed in healthy HIV uninfected and aviremic ART-controlled HIV-infected subjects. These established that (1) healthy HIV negative subjects had robust antibody responses, maximal with 1 mg TUTI-16, (2) ART-controlled aviremic HIV infected subjects had similarly robust antibody responses, and (3) adjuvant-induced increases of HIV viral load did not occur in the presence of ART. These studies provided us a basis for the design of a protocol to explore the therapeutic potential of TUTI-16 vaccination to provide drug free control of HIV-1 viremia.

Interleukin‐17 regulates visceral obesity in HIV‐1‐infected patients

The aim of the study was to evaluate the interleukin-17 (IL-17) plasma level in HIV-1-infected patients and its relation to central obesity. Eighty-four HIV-1-infected patients [42 with visceral obesity (group A) and 42 without visceral obesity (group B)] and 46 HIV-negative subjects [23 with visceral obesity (group C) and 23 without visceral obesity (group D)] were enrolled in the study. Sonographic measurements of perirenal fat diameter/body mass index (PRFD/BMI) were used to assess visceral adipose tissue thickness. HIV-1-infected patients had higher plasma levels of IL-17 than HIV-negative subjects [837.8 ± 260 pg/mL (mean ± standard deviation) vs. 395.3 ± 138.6 pg/mL, respectively; P<0.001]. Furthermore, HIV-1-infected patients with a diagnosis of visceral obesity had lower levels of IL-17 than HIV-infected lean patients (756.9 ± 282.9 pg/mL vs. 918.7 ± 208.4 pg/mL, respectively; P<0.01). IL-17 (r= -0.21; P=0.03) and waist circumference (r=0.48; P<0.001) were significantly associated with visceral adipose tissue thickness. A negative correlation of IL-17 (r= -0.23; P<0.001) with PRFD/BMI was found. This study suggests a linear negative association between IL-17 and visceral adipose tissue thickness.

Prefrontal Dopaminergic and Enkephalinergic Synaptic Accommodation in HIV-associated Neurocognitive Disorders and Encephalitis

Changes in synapse structure occur in frontal neocortex with HIV encephalitis (HIVE) and may contribute to HIV-associated neurocognitive disorders (HAND). A postmortem survey was conducted to determine if mRNAs involved in synaptic transmission are perturbed in dorsolateral prefrontal cortex (DLPFC) in subjects with HIVE or HAND. Expression of the opioid neurotransmitter preproenkephalin mRNA (PENK) was significantly decreased in a sampling of 446 brain specimens from HIV-1 infected people compared to 67 HIV negative subjects. Decreased DLPFC PENK was most evident in subjects with HIVE and/or increased expression of interferon regulatory factor 1 mRNA (IRF1). Type 2 dopamine receptor mRNA (DRD2L) was decreased significantly, but not in the same set of subjects with PENK dysregulation. DRD2L downregulation occurred primarily in the subjects without HIVE or neurocognitive impairment. Subjects with neurocognitive impairment often failed to significantly downregulate DRD2L and had abnormally high IRF1 expression. Conclusion: Dysregulation of synaptic preproenkephalin and DRD2L in frontal neocortex can occur with and without neurocognitive impairment in HIV-infected people. Downregulation of DRD2L in the prefrontal cortex was associated with more favorable neuropsychological and neuropathological outcomes; the failure to downregulate DRD2L was significantly less favorable. PENK downregulation was related neuropathologically to HIVE, but was not related to neuropsychological outcome independently. Emulating endogenous synaptic plasticity pharmacodynamically could enhance synaptic accommodation and improve neuropsychological and neuropathological outcomes in HIV/AIDS.

Human Immunodeficiency Virus-Associated Lipodystrophy: An Objective Definition Based on Dual-Energy X-RAY Absorptiometry-Derived Regional Fat Ratios In A South Asian Population

To develop an objective definition of human immunodeficiency virus (HIV)-associated lipodystrophy by using regional fat mass ratios and to assess the utility of anthropometric and skinfold measurements in the initial screening for lipodystrophy. Male patients between 25 and 50 years old with proven HIV infection (highly active antiretroviral therapy [HAART]-naïve subjects and those receiving successful HAART) were studied and compared with body mass index (BMI)-matched HIV-negative control subjects. Anthropometric variables, body composition, dual-energy x-ray absorptiometry findings, and metabolic variables were compared among the 3 study groups and between those patients with and those without lipodystrophy. Trunk fat/lower limb fat mass ratio >2.28 identified 54.3% of patients with HIV receiving HAART as having lipodystrophy and had the highest odds ratio for predicting metabolic syndrome. The "clinical diagnosis of lipodystrophy" and the "clinical scoring system" had too many false-positive and false-negative results. Triceps skinfold thickness (SFT)/BMI ratio ≤0.49 and abdominal SFT/triceps SFT ratio >1.385 have good sensitivity but poor specificity in identifying lipodystrophy. In comparison with HAART-naïve patients with HIV, those receiving HAART had significantly higher insulin resistance, and a significantly greater proportion had impaired glucose tolerance and dyslipidemia. Among patients receiving HAART, those with lipodystrophy had a greater degree of insulin resistance, higher triglyceride levels, and lower levels of high-density lipoprotein cholesterol. The trunk fat/lower limb fat mass ratio in BMI-matched normal subjects can be used to derive cutoff values to define lipodystrophy objectively in HIV-infected patients. Defining lipodystrophy in this way is better than other methods of identifying those patients with increased cardiovascular risk. Triceps SFT/BMI and abdominal SFT/triceps SFT ratios may be useful as screening tools in resource-poor settings.

Microbiologic profile of endodontic infections from HIV− and HIV+ patients using Multiple‐Displacement Amplification and Checkerboard DNA‐DNA Hybridization

To compare the microbiota of endodontic infections in necrotic pulp from HIV-negative and HIV-positive subjects. Root canal samples from necrotic pulp were collected from 40 HIV- and 20 HIV+ subjects. Pulps were amplified using multiple displacement amplification (MDA). Then, checkerboard DNA-DNA hybridization was employed to assess the levels of 107 microbial taxa. The percentage of DNA probe count and the percentage of teeth colonized by each test species were investigated. Significant differences between groups regarding proportions of taxa and prevalence of the test species were sought using the Mann-Whitney test and the Chi-square analysis, respectively. The most prevalent taxa detected were Dialister pneumosintes, Stenotrophomonas maltophilia, Streptococcus sobrinus, Corynebacterium diphteriae, and Helicobacter pylori among HIV- subjects and D. pneumosintes, Prevotella tannerae, Porphyromonas gingivalis, Parvimonas micra, Prevotella nigrescens, and Corynebacterium diphtheriae among HIV+ individuals. D. pneumosintes, C. diphtheria, and C. albicans were the most abundant species in the HIV- group, whereas the predominant taxa in HIV+ samples were P. tannerae, D. pneumosintes and Olsenella uli. P. tannerae, O. uli, Veilonella dispar, Bacteroides fragilis, and Actinomyces meyeri were significantly more abundant in HIV+ samples. There were significant differences in the prevalence and proportions of specific microbial taxa between HIV- and HIV+ individuals. The root canal microbiota may represent a reservoir of important oral and medical pathogens, mainly in HIV+ individuals.