Asymptomatic HIV-infected Patients Research Articles

Prevalence and Factors Associated with a Prolonged QTc Interval in a Cohort of Asymptomatic HIV-Infected Patients

We aimed to determine the prevalence of a prolonged QTc interval in HIV-infected patients and its related factors through an observational study of a cohort of asymptomatic HIV-infected outpatients. All patients underwent a standard 12-lead electrocardiogram and a transthoracic echocardiogram. Prolonged QTc was considered if it was >440 ms in men and >450 ms in women. Epidemiological, clinical, and laboratory data were collected and the patients completed a questionnaire about cardiovascular risk factors. The analysis of the potential risk factors for prolonged QTc was done by multivariate logistic regression. The study included 194 patients, 84% men, with a mean age of 46.3 years. The mean duration of HIV infection was 122.6 months and 27.8% had AIDS. Antiretroviral therapy was being taken by 185 (96.4%) patients, and 92.4% of them had an undetectable viral load. The mean CD4 lymphocyte count was 553/mm(3). A total of 24 (12.4%) patients had a prolonged QTc interval, with a mean QTc of 456 ms. The factors associated with a prolonged QTc were hyperlipidemia (OR 3.7, 95% CI: 1.3-10.3; p=0.01) and diastolic dysfunction (OR 6.7, 95% CI: 2.4-18.3; p=0.0001), while the use of atazanavir was associated with a lower likelihood of having a prolonged QTc (OR 0.11, 95% CI: 0.02-0.5; p=0.008). A prolonged QTc syndrome was not uncommon in this cohort of asymptomatic HIV-infected patients with good immunovirological control. It was associated with hyperlipidemia and diastolic dysfunction. The use of atazanavir, compared with other protease inhibitors, was associated with a lower likelihood of having a prolonged QTc.

Abnormal Liver Stiffness Assessed Using Transient Elastography (Fibroscan®) in HIV-Infected Patients without HBV/HCV Coinfection Receiving Combined Antiretroviral Treatment

Background and AimsLiver stiffness measurement (LSM) using transient elastography (Fibroscan®) can identify individuals with potential underlying liver disease. We evaluated the prevalence of abnormal LSM values as assessed using LSM and its predictors in HIV-infected asymptomatic patients receiving combined antiretroviral treatment (cART) without HBV/HCV coinfection.MethodsWe prospectively recruited 93 patients who had consistently been undergoing cART for more than 12 months at Severance Hospital in Seoul, Republic of Korea, from June to December 2010. LSM values >5.3 kPa were defined as abnormal.ResultsThirty-nine (41.9%) had abnormal LSM values. On multivariate correlation analysis, the cumulative duration of boosted and unboosted protease inhibitors (PIs) were the independent factors which showed a negative and positive correlation to LSM values, respectively (β = –0.234, P = 0.023 and β = 0.430, P<0.001). In multivariate logistic regression analysis, the cumulative exposure duration of boosted-PIs and γ-glutamyltranspeptidase levels were selected as the independent predictors which showed a negative and positive correlation with abnormal LSM values, respectively (odds ratio [OR], 0.941; 95% confidence interval [CI], 0.889–0.997; P = 0.039 and OR, 1.032; 95% CI, 1.004–1.060; P = 0.023).ConclusionThe high percentage of HIV-infected asymptomatic patients receiving cART without HBV/HCV coinfection had abnormal LSM values. The cumulative exposure duration of boosted-PIs and γ-GT level were independent predictors which showed a negative and positive correlation with abnormal LSM values, respectively.

Immunological, hematological and biochemical parameters are changed in asymptomatic HIV-infected patients, treated or not with antiretroviral drugs

Event Abstract Back to Event Immunological, hematological and biochemical parameters are changed in asymptomatic HIV-infected patients, treated or not with antiretroviral drugs Karen I. Tasca1*, Caio C. Camargo1, Mariana Gatto1, Mônica B. Mendes1 and Lenice R. Souza1 1 Univ Estadual Paulista - UNESP, Tropical Disease, Brazil In HIV-infected even during antiretroviral therapy (ART) and absence of symptoms, the imbalance in immunological, hematological and biochemical factors can potentially contribute to progression to AIDS or other comorbidities. We aimed to analyze some of these parameters in 58 asymptomatic HIV-patients: ART-naïve (HIVn, n=18); virologic failure on ART (HIVf, n=18); on ART and complete viral suppression (HIVc, n=22). Quantification of viral load and CD4+ T cells were done by branched-DNA and flow cytometry, respectively. Sandwich immunosorbent assays were performed to quantify cytokines as IFN-g, TNF-a, IL-10 and IL-6. Other results were collected from medical records. Tukey-Kramer test and negative binomial and gamma distributions were calculated (p<0.05). Comparing three groups, we found the lowest levels of IL-10 in HIVc. The HIVf presented the lowest concentration of IFN-g and the highest levels of TNF-a and IL-6. To lymphocytes, mainly CD4+ T, HIVf presented lower counts than other groups. Triglycerides, high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) were higher in treat-patients (HIVc and HIVf) than HIVn. Total cholesterol was elevated in HIVc when was compared to HIVn, without difference to HIVf. An intriguing result was the higher aspartate-aminotransferase(AST) value found in HIVn than HIVc. When we checked the normal references ranges, the most common changes in the studied population were observed to neutrophils, total leukocytes, hematocrit, creatinine and metabolic exams. Thereby, therapeutic advances have contributed to the slower evolution to AIDS, however the laboratory changes observed in HIV+ deserve to be better understood in order to seek a greater -and better- longevity. Keywords: hiv/aids, Laboratorial changes, HIV-asymptomatics, antiretroviral drugs, Cytokines Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Tasca KI, Camargo CC, Gatto M, Mendes MB and Souza LR (2013). Immunological, hematological and biochemical parameters are changed in asymptomatic HIV-infected patients, treated or not with antiretroviral drugs. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00552 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 May 2013; Published Online: 22 Aug 2013. * Correspondence: Miss. Karen I Tasca, Univ Estadual Paulista - UNESP, Tropical Disease, Botucatu, SP, Brazil, karenitasca@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Karen I Tasca Caio C Camargo Mariana Gatto Mônica B Mendes Lenice R Souza Google Karen I Tasca Caio C Camargo Mariana Gatto Mônica B Mendes Lenice R Souza Google Scholar Karen I Tasca Caio C Camargo Mariana Gatto Mônica B Mendes Lenice R Souza PubMed Karen I Tasca Caio C Camargo Mariana Gatto Mônica B Mendes Lenice R Souza Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Coronary vessel wall thickening in asymptomatic young HIV-infected patients vs. controls using phase-sensitive dual inversion recovery (PS-DIR) MRI

Background HIV-infected patients demonstrate premature and more severe vascular disease relative to controls. Therefore, development of a reproducible non-invasive vascular imaging biomarker in this population is important. The purpose of this study was to assess coronary artery wall thickness in young HIV-infected patients who acquired HIV in early life compared to healthy controls using a novel black-blood coronary vessel wall MR imaging technique.

Echocardiographic Abnormalities and Associated Factors in a Cohort of Asymptomatic HIV-Infected Patients

HIV patients have been reported to have a greater prevalence of echocardiographic abnormalities. We aimed to determine the prevalence of these abnormalities and their associated factors. This was an observational study of a cohort of asymptomatic HIV patients. Data were recorded on factors of cardiovascular interest and those related to HIV infection. All the subjects underwent a transthoracic echocardiogram. The study included 196 patients, 85.2% men, mean age 46.4 years, with a mean duration of HIV infection of 123.8 months and 27.6% with AIDS. Of the patients, 94.4% were on antiretroviral therapy and 92.5% of these had an undetectable viral load. The mean CD4 cell count was 544/mm(3). The following echocardiographic abnormalities were found: left ventricular (LV) hypertrophy 28.6%, LV diastolic dysfunction 19.9%, left atrial (LA) dilatation 7.7%, right ventricular (RV) systolic dysfunction 6.1%, pulmonary hypertension 2.6%, RV dilatation 2%, and (LV) systolic dysfunction 1%. LV hypertrophy was associated with diabetes mellitus (OR 5.3, 95% CI 1.8-15.3; p=0.001), LV diastolic dysfunction with age (OR for each extra 5 years 4.4, 95% CI 4.2-4.6; p=0.0001), obesity (OR 4.07, 95% CI 1.6-10.0; p=0.02), alcohol consumption (OR 2.5, 95% CI 1.07-6.2; p=0.03) and lower CD4 cell count (OR for each 10 CD4 cells less 10.02, 95% CI 10.00-10.04; p=0.008), and RV systolic dysfunction with hypertension (OR 5.4, 95% CI 1.6-18.2; p=0.005). Echocardiographic abnormalities in HIV patients were common, especially LV hypertrophy and diastolic dysfunction. Prospective comparative studies involving the general population are needed to determine the prevalence of HIV infection and its treatment in these abnormalities.

High Prevalence of Pulmonary Arterial Hypertension in a Cohort of Asymptomatic HIV-Infected Patients

HIV infection is considered a risk factor for the development of pulmonary arterial hypertension (PAH) and the estimated prevalence of PAH in developed countries is 0.5%. The aim of this study was to determine the prevalence of PAH in a cohort of HIV-infected patients and the related factors. We undertook an observational study of a consecutive cohort of asymptomatic HIV-infected patients. Data were recorded about factors of cardiovascular interest and factors related to HIV infection. All the patients underwent a transthoracic echocardiogram (Vivid S6, GE Healthcare). PAH was considered to be a pulmonary arterial systolic pressure (PASP) >40 mm Hg. The study included 194 patients (85.2% men) with a mean age of 47.0 years, 94% of whom were on antiretroviral therapy (ART). The mean CD4 lymphocyte count was 495/mm(3). The mean duration of HIV infection was 131.5 months, and 28.4% had experienced an AIDS event. PAH was present in five patients (2.6%) and 14 were in the gray zone (PASP of 36-40 mm Hg). These five patients were men, the route of transmission was homosexual, and they were all on ART. They were also older than the patients without PAH (57.7 vs. 46.4 years, p=0.02) and had been on ART for longer (180.0 vs. 92.5 months; p=0.01). No association was found with any of the other parameters. The prevalence of PAH in this cohort of patients was greater than in other published series. The only associations found were with older age and longer ART time.

Urethritis/Cervicitis Pathogen Prevalence and Associated Risk Factors Among Asymptomatic HIV-Infected Patients in South Africa

To determine sexually transmitted infection (STI) prevalence, and patient characteristics associated with detection of urethritis/cervicitis pathogens, among HIV-infected individuals offered voluntary STI screening at a South African HIV treatment center. Individuals, asymptomatic for genital discharge, were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) infections (real-time polymerase chain reaction assay), for syphilis and herpes simplex type 2 (serologically), and for bacterial vaginosis and Candida (microscopy, women only). Patients' most recent CD4 and viral load results were recorded. Demographic, clinical, and behavioral data were collected by nurse-administered questionnaire. Compared with men (n = 551), women (n = 558) were younger (mean age, 35.0 vs. 37.9 years; P < 0.001), reported more STIs in the past year (65.5% vs. 56.5%; P = 0.002), had more urethritis/cervicitis pathogens detected (21.3% vs.16.4%, P = 0.035), and were less aware of their partner's HIV status (53.1% vs. 62.3%; P = 0.007). The overall prevalence of individual urethritis/cervicitis pathogens was TV (7.6%), MG (6.1%), NG (5.4%), and C. trachomatis (2.1%). Multivariate analysis highlighted 4 significant factors associated with the detection of specific urethritis/cervicitis pathogens, namely female gender (TV, adjusted odds ratio [aOR] 2.53, 95% confidence interval [CI]: 1.47-4.37), having a regular sexual partner in the past 3 months (NG, aOR 2.26, 95% CI: 1.01-5.08), suboptimal condom use with regular partners (TV, aOR 2.07, 95% CI: 1.25-3.42), and a history of genital warts in the past year (NG, 2.25, 95% CI: 1.26-4.03). Asymptomatic urethritis/cervicitis pathogens were highly prevalent in this population. Few urethritis/cervicitis pathogen-associated patient characteristics were identified, emphasizing the need for affordable STI diagnostics to screen HIV-infected patients.

Low prevalence of asymptomatic sexually transmitted infections in HIV-infected heterosexuals visiting an HIV clinic in the Netherlands

Two-hundred and forty-five heterosexual HIV-infected patients (58% women; median age 41 years) were screened for asymptomatic sexually transmitted infections (STIs) during a routine visit at a large HIV outpatient clinic in the Netherlands. High-risk sexual behaviour was rare and STI prevalence was low: three Chlamydia trachomatis infections and one case of syphilis were diagnosed. These results suggest that, in the Netherlands, screening for STI during routine visits is currently not needed for asymptomatic heterosexual HIV-infected patients.

IgG anti-toxoplasma antibodies among asymptomatic HIV-infected patients in Marrakesh-Morocco

Detection and monitoring of anti-Toxoplasma gondii antibodies are of a great interest among human immunodeficiency virus (HIV)-infected patients, since cerebral toxoplasmosis is a life-threatening opportunistic infection within this vulnerable population. The IgG anti-T. gondii seroprevalence was assessed in 95 asymptomatic HIV-infected adults living in Marrakesh city and its surrounding areas. Our results showed a seroprevalence of 62.1%, which is high compared to most other countries. The mean of CD4+ T-cells count of involved patients was 381.9cells/μl. Given these results, HIV-infected patients in Marrakesh region could be at high risk to develop toxoplasmosis disease, especially when CD4+ T-cells count falls below 100cells/μl. Accordingly, there is a serious need of widening antiretroviral therapy and chemoprophylaxis against toxoplasmosis, when indicated, to ovoid toxoplasmosis reactivation among this population.

Longitudinal assessment of cardiac diastolic function in HIV-infected patients

Asymptomatic isolated diastolic dysfunction (DD), with normal left ventricular systolic function, may be the first indication of underlying cardiac disease in HIV-negative populations. We previously reported a high prevalence (37%) of DD among asymptomatic HIV-infected patients at low risk for AIDS and cardiovascular disease (CVD). We performed a longitudinal assessment of interval echocardiographic changes in this cohort over a four-year period. Repeat transthoracic echocardiograms (TTEs) utilized standard techniques. Sixty (of the original 91) HIV-infected patients, predominately men, underwent repeat TTE (median follow-up 3.7 years, interquartile range [IQR] 3.5, 4.0). Cohort characteristics (median; IQR) include age 42.0 (36.5, 46.0) years, HIV duration 16.4 years (8.1, 18.9), current CD4 count 572.0 cells/mm(3) (436.5, 839.0), antiretroviral therapy (ART) duration 8.1 years (4.8, 13.4) and Framingham risk score 1.0 (0.0, 2.0). DD was observed in 28/60 patients on re-evaluation (47%, 95% confidence interval [CI] 34%, 60%); 31% (11/36) of patients had new onset DD for an overall incidence of 8.2/100 person-years. On follow-up, subjects with DD were older, had a trend towards higher body mass index, hypertension and longer duration of HIV infection compared with subjects without DD. We confirmed a high prevalence of DD (47%) in asymptomatic HIV-infected patients at low risk for AIDS and CVD.

Effects of HAART on Platelet-Activating Factor Metabolism in Naive HIV-Infected Patients I: Study of the Tenofovir-DF/Emtricitabine/Efavirenz HAART Regimen

Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein-associated-phospholipase-A(2) (LpPLA(2)) in plasma, were measured in blood samples of eight asymptomatic naive male HIV-infected patients just before and after 1, 3, and 6 months of treatment. CD4 cell counts, viral load, and several biochemical markers were also measured in the same blood samples of these patients. The repeated measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations-partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA(2) in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF-biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA(2) remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir-DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated.

CD4+CD38+HLA-DR+ Cells: a Predictor of Viral Set Point in Chinese Men with Primary HIV Infection Who Have Sex with Men

Twenty-three Chinese men with primary HIV infection (PHI) who have sex with men, and 17 asymptomatic HIV-infected patients participated in this study. The effect of different initial activation parameters on viral set points and the immunologic progression of subjects with PHI were determined. We found that the proportions of CD38+DR+ and CD38-DR+ T cells were lower while those of CD38+DR- and CD38-DR- T cells were higher in patients with PHI than in the asymptomatic HIV-infected patients. The initial proportion of CD4+CD38+DR+ T cells emerged as a statistically significant predictor (P < 0.05) of viral set points by multivariate least squares regression. In addition, individuals with a higher initial proportion of CD4+CD38+DR+ cells were more likely to have CD4+ T cell counts decrease to ≤ 350 cells/µl (P = 0.015), as determined by Kaplan-Meier curve analysis. We concluded that the initial CD4+CD38+DR+ T cell level in PHI patients is an important prognostic parameter of viral set points and is therefore related to disease progression.

Alternations of CD+4 CD+25 Foxp3 + regulatory T cells in early HIV infected patients in China

Objective To study the alternations of regulatory T cells in early HIV infected patients and its association with disease progression.Methods Fifty-one untreated HIV infected patients were enrolled and divided into 3 groups according to their infection time and CD+4 T cell levels(30 early HIV infected patients,15 typical progressors,6 AIDS patients).Twenty normal controls were enrolled.There were no significant differences between the age and sex among four groups.Blood was drawn by venipuncture from each subject in EDTA tubes and the levels of CD+4 CD+25 Foxp3 + regulatory T cells were detected by FACSAria flow-cytometry.Spearman correlation was used to detect association between CD+4 CD+25 Foxp3 + regulatory T cells and the absolute CD+4 T cells,viral load and activation of T cells.Results The levels of CD+4 CD+25Foxp3+ regulatory T cells showed the tendency of increasing tendency from normal control to early HIV infected patients,asymptomatic HIV infected patients and AIDS patients.Early HIV infected patients was significantly lower than that in AIDS group [3.79(2.11 - 5.43) % vs 8.09(4.90 - 8.90) %,Z = - 2.29,P = 0.022].The levels of CD+4 CD+25 Foxp3 + Treg cells were associated with viral set point(r = 0.479,P =0.038) and inversely associated with CD+4 T cells(r = -0.455,P =0.011) and closely associated with HLA-DR expression on CD+3 T cells(r = 0.533,P = 0.002).Conclusions The ratio of CD+4 CD+25 Foxp3 +regulatory T cells of early HIV infected patients was significantly increased and associated with viral set point and CD+4 T cell counts,which indicate that alternation of regulatory T cell may be an important factor contributing to the disease progression in early HIV infection. Key words: HIV; Early HIV infection; Regulatory T cell; Activation

Audio‐Vestibular Function in HIV Infected Patients in India

Objective: The impact of HIV/AIDS is felt more in developing countries because of socioeconomic reasons. There is risk of audio vestibular dysfunction with the use of anti-retroviral therapy, which may be ototoxic. This study was to determine the difference between audio-vestibular function in asymptomatic HIV infected and AIDS patients. Method: In this prospective cross sectional study conducted in a tertiary care hospital in South India, the audio-vestibular system of 30 AIDS subjects (group 1) and 30 asymptomatic HIV positive subjects (group 2) and age-matched 30 healthy controls (group 3) were assessed using pure tone audiometry and cold caloric test. Results: Sixteen patients each, in group 1 and group 2, were detected to have hearing loss. In the control group, 4 were detected to have hearing loss. Comparing patient groups 1 and 2 with that of group 3, the p-value was significant ( P = .001). Kobrak’s (modified) test showed 27% of patients in group 1 and 33% of patients in group 2 had a hypofunctioning labyrinth. Conclusion: It was found that the human immunodeficiency virus does affect the audio-vestibular pathway. There was a significant incidence of audio-vestibular dysfunction in both study groups compared to the controls. There was no significant difference between the HIV seropositive asymptomatic patients and patients with AIDS. The majority of the patients had no otological symptoms.

O1-S11.06 Burden of genital discharge pathogens and associated characteristics of asymptomatic HIV-infected patients in Johannesburg, South Africa

BackgroundThe prevalence of asymptomatic STIs and urethritis/cervicitis pathogen-associated patient characteristics were determined among patients attending a HIV treatment centre in Johannesburg.MethodsConsenting consecutive HIV-infected patients, asymptomatic for symptoms/signs of genital discharge,...

Dendritic Cells Exposed to MVA-Based HIV-1 Vaccine Induce Highly Functional HIV-1-Specific CD8+ T Cell Responses in HIV-1-Infected Individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Central Memory CD4 Cells Are an Early Indicator of Immune Reconstitution in HIV/AIDS Patients with Anti-Retroviral Treatment

The number of central memory cells among the CD4+ T cells and the of activation of CD8+ T cells is believed to be a better indicator of immune restoration in patients on antiretroviral therapy (ART) than the absolute numbers of CD4+ and CD8+ T cells alone. In the current study, we investigated the changes in the CD4+ T cell subsets and their association with immune reconstitution and immune activation at early stages of ART. A prospective study was performed in 21 asymptomatic treatment-naive HIV-infected patients with CD4+ T cells less than 350 cells/μl. Blood samples were evaluated at base line, and at 2, 4, 8 and 12 weeks’ post antiretroviral therapy (ART). A biphasic increase of CD4+ T cells, central memory CD4 cells (CD4 CM) and CD4 naïve cells were observed after ART, with a rapid increase before week 4. Change in CD4 CM at week 4 positively correlated with the change in CD4+ T cells at weeks 12 post ART, and negatively correlated with the change in CD8+CD38+ T cells at weeks 12 post ART. We conclude that CD4 CM cells are a major contributor to early immune reconstitution in treatment-naive HIV-infected patients with delayed ART, and might be an early indicator for immune reconstitution.

In Vivo Effects of a Ginkgo Biloba Extract on Platelet Activating Factor Metabolism in Two Asymptomatic Hiv-Infected Patients

Ginkgo biloba products seem to protect from several pathological conditions, including HIV manifestations, where Platelet Activating Factor (PAF) is implicated. In the present study, we examined for the first time the in vivo effects of a standardized formulation of Ginkgo biloba extract (150 mg daily, per os) on PAF metabolism in blood cells and plasma of two male, asymptomatic HIV-infected patients, not receiving antiretroviral treatment, during a 9-month period. These patients differed at baseline in terms of duration of HIV infection, viral load levels, CD4 cell counts and Highly Active Antiretroviral Therapy (HAART) experience. In the first patient with early HIV infection, after an initial transient increase, a return of both plasma viral load and PAF biosynthetic enzyme activities in leukocytes to their baseline levels was observed during Ginkgo biloba use. As a result PAF degradation also remained low in this patient. The second patient with late but not advanced HIV infection, had higher levels of viral load and a lower CD4 cell count at baseline. The use of 150 mg of a Ginkgo biloba extract was probably insufficient to induce PAF degradation and/or to suppress the induction of PAF biosynthesis observed. At the same time, the initial high levels of viral load were further increased and CD4 cell counts were finally decreased during the study. The observed differences in PAF metabolism during Ginkgo use seem to be related to the initial heterogeneity of these patients. It appears that in some HIV-infected patients inhibition of the PAF/PAF-receptor system, along with a decrease/down-regulation of PAF-biosynthesis, illustrates a new potential role for Ginkgo biloba compounds in the treatment of HIV infection and its manifestations. However, more tests on a larger number of patients are needed in order to support these preliminary observations.

Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients

Despite the availability of potent antiretroviral regimens (combination antiretroviral therapy [cART]), HIV-associated neurocognitive disorders (HAND) are increasingly recognized. Our aim was to investigate the prevalence and treatment-related correlates of HAND, exploring the potential neurotoxicity of antiretrovirals on cognitive functions. We performed a cross-sectional single cohort study by consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits. Each patient was submitted to a comprehensive neuropsychological battery and was considered cognitively impaired on the basis of results obtained in matched healthy HIV-negative subjects. CNS penetration effectiveness (CPE) rank was calculated for cART regimens according to 2010 CHARTER criteria. Factors associated with cognitive impairment were investigated by linear or logistic regression analysis. A total of 146 patients were enrolled. Of these, 129 (88.4%) were on cART and 59.6% of them were on current regimen from ≥1 year. Sixty-nine patients (47%) were classified as cognitively impaired (35.6% asymptomatic and 11.6% mild neurocognitive impairment). In the multivariate analysis, efavirenz use (odds ratio [OR] = 4.00; p = 0.008) and non-Italian nationality (OR = 3.46; p = 0.035) were associated with increased risk of cognitive impairment, whereas higher education was associated with a lower risk (OR = 0.85; p = 0.002). Furthermore, efavirenz use and age ≥65 years independently predicted worse performance on the double barrage and the Stroop test (time). No association between CPE rank and cognitive impairment was observed. A high prevalence of HAND was observed in apparently asymptomatic HIV+ individuals. HAND was associated with efavirenz use, suggesting the potential neurotoxicity of this drug. Routine neuropsychological examinations could help clinicians make correct diagnoses and manage mild, but clinically relevant, forms of HAND.

Characteristics of CD8+ T cell subsets in Chinese patients with chronic HIV infection during initial ART

BackgroundCD8+ T cells may play an important role in protecting against HIV. However, the changes of CD8+ T cell subsets during early period of ART have not been fully studied.MethodsTwenty-one asymptomatic treatment-naive HIV-infected patients with CD4 T+ cells less than 350 cells/μl were enrolled in the study. Naïve, central memory(CM), effective memory(EM) and terminally differentiated effector (EMRA) CD8+ cell subsets and their activation and proliferation subsets were evaluated in blood samples collected at base line, and week 2, 4, 8 and 12 of ART.ResultsThe total CD8+ T cells declined and the Naïve and CM subsets had a tendency of increase. Activation levels of all CD8+ T cell subsets except EMRA subset decreased after ART. However, proliferation levels of total CD8+ T cells, EMRA, EM and CM subsets increased at the first 4 weeks of ART, then decreased. Proliferation level of the naïve cells decreased after ART.ConclusionThe changes of CD8+ T cell subsets during initial ART are complex. Our results display a complete phenotypical picture of CD8+ cell subsets during initial ART and provide insights for understanding of immune status during ART.