CD4+T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes

P>Human immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4-23, 45-64 and 73-95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4+ and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells.

Is alcohol a cofactor of HIV and AIDS? Evidence from immunological and behavioral studies

The authors aim to critically examine empirical research on the effects of alcohol on HIV and AIDS from the immunological and behavioral fields. In vitro immunological studies demonstrate that social drinking increases the susceptibility of human cells to HIV infection. Animal studies show that acute and chronic alcohol ingestion increases rare of progression from retrovirus to clinical illness. In humans with HIV, no experimental evidence shows that alcohol is a cofactor of AIDS. Findings from behavioral studies show that a link between social drinking and risk of HIV is weak. No experimental evidence demonstrates that chronic drinking influences rate and course of disease progression to AIDS in humans who are HIV+. It is premature to promote the role of alcohol as a cofactor in HIV and AIDS.

Subclinic atherosclerosis and cardiovascular risk factors in HIV-infected children: PERI study

Objectives To compare carotid intima-media thickness (cIMT) of children and adolescents with and without HIV infection and to determine associations among independent socio-demographic, clinical or cardiovascular variables and cIMT in HIV-infected children and adolescents. Patients and methods This is a matched case-control study comparing 83 HIV-infected and 83 healthy children and adolescents. Clinical and laboratorial parameters, cIMT and echocardiogram were measured. Results The cIMT was higher in HIV-infected individuals (median 480 mu m; interquartile range 463-518 mu m) compared with controls (426 mu m; range 415-453 mu m, P < 0.001). In addition, the HIV-infected group showed higher levels of high-sensitive C-reactive protein (medians 1.0 mg/l vs. 0.4 mg/l, P < 0.001), glycated hemoglobin (6.1 +/- 0.9 vs. 5.7 +/- 0.8%, P= 0.028) and triglycerides (medians 0.9 vs. 0.8 mmol/l, P= 0.031). Finally, this group showed lower levels of total and high-density lipoprotein-cholesterol. After multivariate analysis, increased cIMT was positively associated with stavudine use [odds ratio (OR): 18.9, P=0.005], left atrial/aorta index (OR: 15.6, P=0.019), suprailiac skinfold (OR: 7.9, P=0.019), tachypnea (OR: 5.9, P=0.031), CD8 lymphocyte count (OR: 5.7, P=0.033) and CD4 T-lymphocyte count (OR: 5.5, P=0.025). cIMT increment was negatively associated with total cholesterol (OR: 0.2, P=0.025) and with CD8 zenith (OR: 0.1, P=0.007). Conclusion In this sample of children and adolescents, having HIV infection was associated with increased cIMT and elevated prevalence of cardiovascular risk factors. These findings suggest that this group should be included in cardiovascular prevention programs.

Language strategies in the attribution of blame for HIV and AIDS

This article examines the language strategies used in everyday explanation by young heterosexual adults to attribute blame for the transmission of HIV: Seventy-two-female and 60 male Australian university students took part in the study. They were formed into groups of four, with each group taking part in discussions about HIV: AIDS, and related matters. Transcripts were examined for instances of blaming, and a coding scheme for levels of attributed responsibility applied to those instances found. Language strategies of distancing self from HN and AIDS were then coded, including checks for who was blamed whether they were members of participants' ingroups or outgroups, and whether justifications were used. These findings are discussed in terms of positioning the self vis-a-vis HIV and AIDS, as well as the ways in which negative stereotypes were used in attributing blame to members of outgroups.

Supporting contexts in program refinement

A program can be refined either by transforming the whole program or by refining one of its components. The refinement of a component is, for the main part, independent of the remainder of the program. However, refinement of a component can depend on the context of the component for information about the variables that are in scope and what their types are. The refinement can also take advantage of additional information, such as any precondition the component can assume. The aim of this paper is to introduce a technique, which we call program window inference, to handle such contextual information during derivations in the refinement calculus. The idea is borrowed from a technique, called window inference, for handling context in theorem proving. Window inference is the primary proof paradigm of the Ergo proof editor. This tool has been extended to mechanize refinement using program window inference. (C) 1997 Elsevier Science B.V.

Better CD4+T Cell Recovery in Brazilian HIV-Infected Individuals Under HAART Due to Cumulative Carriage of SDF-1-3`A, CCR2-V64I, CCR5-D32 and CCR5-Promoter 59029A/G Polymorphisms

Polymorphisms of chemokines and chemokine-receptors genes have been shown to influence the rate of progression to AIDS; however, their influence on response to HAART remains unclear. We investigated the frequency of the SDF-1-3`A, CCR2-64I, CCR5-D32 and CCR5-Promoter-59029-A/G polymorphisms in Brazilian HIV-1-infected and uninfected individuals and their influence on CD4+ T-cell evolution HIV-1 infected individuals before and during HAART. Polymorphism detection was done in a transversal study of 200 HIV-1-infected and 82 uninfected individuals. The rate of CD4+ T cell increase or decrease was studied in a cohort of 155 HIV-1 infected individuals on pre and post-HAART. Polymorphisms were determined by PCR associated with RFLP. The rate of CD4+ T-cell decline or increase was also determined. HIV-1 infected and uninfected subjects showed, respectively, frequencies of 0.193 and 0.220 for SDF-1-3`A, of 0.140 and 0.110 for CCR2-V64I, of 0.038 and 0.055 for CCR5-D32, and of 0.442 and 0.390 for CCR5-P-59029-A/G. HIV-1-infected subjects carrying one, two or three of these four polymorphisms showed better CD4+ T-cell recovery than HIV-1-infected subjects carrying the four wild-type alleles (+2.7, +1.6, +3.5, and -0.9 lymphocytes/mu l/month, respectively). Regression logistic analysis showed that the CCR5-D32/CCR2-V64I association was predictor of positive CD4+ T cell slope after HAART. The distribution of polymorphisms did not differ between HIV-1-infected and uninfected individuals, but differed from more homogenous ethnic groups probably reflecting the miscegenation of the Brazilian population. We add further evidence of the role of these polymorphisms by showing that the CD4 gain was influenced by carriage of one or more of the polymorphisms studied here. These results highlight the possibility that these genetic traits can be useful to identify patients at risk for faster progression to AIDS or therapeutic failure.

Effect of aquatic respiratory exercise-based program in patients with fibromyalgia

Objective: This study assessed the effects of an aquatic respiratory exercise-based program in patients with fibromyalgia (FMS). Methods: Forty women, aged between 20 and 60 years, were randomly assigned into two groups of 20 patients: the aquatic respiratory exercise-based program (ARG) and the control group (CTL). The ARG group performed the exercise program for 1 h, four times a week, for 4 weeks which included: (i) warming-Lip; (ii) respiratory exercises, consisting of five different breathing patterns, along With upper, lower limbs and trunk movements (45 min); and (iii) relaxation exercises. Both groups were included in supervised recreational activities of 1 h, once a week, for 4 weeks. Questionnaires were applied before and after intervention to assess quality of life and functional capacity (SF-36, Fibromyalgia Impact Questionnaire [FIQ]), anxiety (Hamilton Anxiety Scale [HAS]), and quality of sleep (Pittsburg Sleep Quality Index [PSQI]). Number of tender points and pain (Visual Analogue Scale [VAS]) were also evaluated. Results: At baseline there was no difference between the two groups, including number of tender points and questionnaire responses. After intervention, the ARG group, compared with the CTL group, showed improvement in SF-36 scores (physical functioning P = 0.001, bodily pain 1) = 0.001, vitality P = 0.009, social functioning P = 0.001, emotional role P = 0.001), in FIQ (total score P = 0.049, work missed P = 0.036, fatigue P = 0.013, morning tiredness P = 0.007) plus in VAS-pain (P = 0.029), VAS-dyspnea (P = 0.04), anxiety (HAS P = 0.005) and quality of sleep (PSQI P = 0.004). Conclusions: The short-term aquatic respiratory exercise-based program improved pain, quality of life, functional capacity, anxiety and quality of sleep in patients with FMS and may be a relevant addition to the treatment of these patients.

FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC(3) program

Background & Aims: EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Methods: Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy. Results: Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3, and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2 = 0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p <= 0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p <= 0.001): genotype 2/3 (odds ratio = 2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5). Conclusions: FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12 weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Surgical Outcomes after Preceptored Laparoscopic Colorectal Surgery: Results of a Brazilian Preceptorship Program

Background/Aims: Safety of laparoscopic colectomy education methods remains unknown. This study aimed at comparing the outcomes of patients undergoing preceptored laparoscopic colectomy with patients operated on by the same preceptor. Methodology: A prospective analysis of 30 preceptored operations performed by nine surgeons (PD group) between 2006 and 2008 was conducted. Data of 30 operations matched for diagnosis and surgery type conducted by the same preceptor (P group) were evaluated. Results: Median age was 56.2 (26-80) and 55.2 (22-81) respectively in P and PD group (p=0.804). Eleven (36.7%) were male in P group, 16 (53.3%) in PD group (p=0.194). Preceptored operations were not significantly longer than operations performed by the preceptor (198 vs. 156 min) - p=0.072. Length of hospital stay did not differ [4 days (3-12) in P group, and 5 (3-15) in PD group, p=0.296]. Conversion occurred in 4 cases in PD and in 2 in P group (p=0.389). Morbidity was similar (23.3% in P and 26.7% in PD group). One patient from P and two from PD group needed re-operation. No deaths occurred. Conclusions: Laparoscopic colorectal surgery preceptorship programs in surgeon learner`s place are safe. Surgeons` introduction through basic and hands-on courses is required for skills acquisition needed to minimize adverse outcomes.

Screening Anal Dysplasia in HIV-Infected Patients: Is There an Agreement Between Anal Pap Smear and High-Resolution Anoscopy-Guided Biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system (""without dysplasia"" and ""with dysplasia of any grade""). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

Gastroduodenal opportunistic infections and dyspepsia in HIV-infected patients in the era of Highly Active Antiretroviral Therapy

Background and Aim: Dyspeptic symptoms are frequently reported by human immuno-defficiency virus (HIV)-infected patients under highly active antiretroviral therapy. Whether opportunistic infections are a cause of dyspepsia is still unknown. In this study we prospectively compare the prevalence of gastrointestinal opportunistic infections in dyspeptic versus non-dyspeptic HIV-infected patients with advanced immunodeficiency. Patients and Methods: Six hundred and ninety HIV-infected patients under highly active antiretroviral therapy underwent esophagogastroduodenoscopy with mucosal biopsies from the stomach and duodenum. Group 1: 500 patients (161 women, 339 men; mean age 38.8 years; mean CD4 count 154.3 cells/mm(3) with dyspeptic symptoms such as epigastric pain, nausea, vomiting and fullness. Group 2: 190 patients (169 men, 21 women; mean age 40.7 years; mean CD4 count 171.6 cell/mm(3)) with no dyspeptic symptoms. Results: Group 1: Gastrointestinal opportunistic infections were observed in eight (1.6%), and non-opportunistic parasites in two (0.4%), patients. They were: Cytomegalovirus (four patients), Cryptosporidium sp. (two patients), Schistosoma mansoni sp. (one patient), Strongyloides stercoralis (one patient) and Giardia sp. (two patients). In five patients esophagogastroduodenoscopy showed no mucosal lesions. Group 2: Giardia sp. was detected in two patients (1.1%: P = 0.07947). Conclusion: Gastrointestinal opportunistic infections were shown in a small number of HIV-infected patients under highly active antiretroviral therapy with advanced immunodeficiency. Although gastrointestinal opportunistic infections were detected exclusively in the dyspeptic patient group, they could not be related to these symptoms, since the number of infected patients was not statistically significant. To correctly diagnose opportunistic infections, multiple biopsy specimens may be necessary even from normal-appearing mucosa.

Detection of nosocomial malnutrition is improved in Amazon region by a standard clinical nutrition education program

Background: In Brazil hospital malnutrition is highly prevalent. physician awareness of malnutrition is low, and nutrition therapy is underprescribed. One alternative to approach this problem is to educate health care providers in clinical nutrition. The present study aims to evaluate the effect of an intensive education course given to health care professionals and students on the diagnosis ability concerning to hospital malnutrition. Materials and methods: An intervention study based on a clinical nutrition educational program, offered to medical and nursing students and professionals, was held in a hospital of the Amazon region. Participants were evaluated through improvement of diagnostic ability, according to agreement of malnutrition diagnosis using Subjective Global Assessment before and after the workshop, as compared to independent evaluations (Kappa Index, k). To evaluate the impact of the educational intervention on the hospital malnutrition diagnosis, medical records were reviewed for documentation of parameters associated with nutritional status of in-patients. The SPSS statistical software package was used for data analysis. Results: A total of 165 participants concluded the program. The majority (76.4%) were medical and nursing students. Malnutrition diagnosis improved after the course (before k = 0.5; after k = 0.64; p < 0.05). A reduction of false negatives from 50% to 33.3% was observed. During the course, concern of nutritional diagnosis was increased W = 17.57; p < 0.001) and even after the course, improvement on the height measurement was detected chi(2) 12.87;p < 0.001). Conclusions: Clinical nutrition education improved the ability of diagnosing malnutrition; however the primary impact was on medical and nursing students. To sustain diagnostic capacity a clinical nutrition program should be part of health professional curricula and be coupled with continuing education for health care providers.

Antiretroviral Drug Resistance in a Respondent-Driven Sample of HIV-Infected Men Who Have Sex With Men in Brazil

Background: There are few studies on HIV subtypes and primary and secondary antiretroviral drug resistance (ADR) in community-recruited samples in Brazil. We analyzed HIV clade diversity and prevalence of mutations associated with ADR in men who have sex with men in all five regions of Brazil. Methods: Using respondent-driven sampling, we recruited 3515 men who have sex with men in nine cities: 299 (9.5%) were HIV-positive; 143 subjects had adequate genotyping and epidemiologic data. Forty-four (30.8%) subjects were antiretroviral therapy-experienced (AE) and 99 (69.2%) antiretroviral therapy-naive (AN). We sequenced the reverse transcriptase and protease regions of the virus and analyzed them for drug resistant mutations using World Health Organization guidelines. Results: The most common subtypes were B (81.8%), C (7.7%), and recombinant forms (6.9%). The overall prevalence of primary ADR resistance was 21.4% (i.e. among the AN) and secondary ADR was 35.8% (i.e. among the AE). The prevalence of resistance to protease inhibitors was 3.9% (AN) and 4.4% (AE); to nucleoside reverse transcriptase inhibitors 15.0% (AN) and 31.0% (AE) and to nonnucleoside reverse transcriptase inhibitors 5.5% (AN) and 13.2% (AE). The most common resistance mutation for nucleoside reverse transcriptase inhibitors was 184V (17 cases) and for nonnucleoside reverse transcriptase inhibitors 103N (16 cases). Conclusions: Our data suggest a high level of both primary and secondary ADR in men who have sex with men in Brazil. Additional studies are needed to identify the correlates and causes of antiretroviral therapy resistance to limit the development of resistance among those in care and the transmission of resistant strains in the wider epidemic.

Genotypic distribution of hepatitis C among hepatitis C and HIV co-infected patients in Brazil

Information on hepatitis C virus (HCV) genotypic distribution among HIV-HCV co-infected patients is lacking in Brazil as well as other Latin American countries. The objective of this study was to evaluate the level of exposure to different risk factors associated with HCV transmission among a group of co-infected patients and to characterize the genotypic distribution of HCV in this cluster. A series of 100 HIV-HCV co-infected patients was analysed. The data to be analysed were collected from specific laboratory tests. Information was collected through a questionnaire. HCV genotyping was carried out by sequencing the 5 ` non-coding region of HCV. Chi-square and Fischer association tests or Kruskal-Wallis test were used to study the association between HCV transmission-related variables and the established genotypes. In conclusion, exposure to multiple risk factors associated with HCV transmission was common among HIV co-infected patients and an association between HCV genotype 3 and intravenous drug user was observed.