摘要:

Local and systemic production of total and HIV-1 specific IgA was determined in whole saliva and serum from 45 HIV-1-infected individuals and 15 healthy controls. The antigenic domains important for sIgA and IgG binding, respectively, was investigated with epitope mapping using synthetic peptides of HIV-1 proteins. Decreased levels of total sIgA in saliva were found among patients with low CD4+cell counts in advanced stages of acquired immunodeficiency. HIV-1 specific IgA response, predominantly directed to the envelope proteins, was found in saliva and serum also at later stages of disease. Analyses using peptide enzyme-linked immunosorbent assays (ELISA) showed that the sIgA antibody response in saliva was mainly directed to the V4 region (aa 385-409) and a more C-terminal part of the V3-region (aa 325-344) compared with the IgG response, which predominantly was directed to a more central part of the V3 loop (aa 308-325). A similar picture was seen for immunoglobulins of the two isotypes derived from serum. We have in this study shown IgA epitope-specific immune response within HIV-1 gp160, indicating that antibodies of IgA isotype may recognize somewhat different antigenic domains compared to IgG antibodies.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Macrophages play a key role in AIDS pathogenesis and thus controlling infectivity and viral replication in these cells is a key issue in any antiretroviral therapy. In the present study, using a murine model of AIDS, we evaluated new therapeutic approaches specifically designed for the protection of macrophages. Based on previous observations, we took advantage of the unique ability of autologous erythrocytes to deliver drugs selectively to macrophages. The antiviral drugs selected were a new homodimer of AZT (AZTp2AZT) and reduced glutathione (GSH). The addition of an oral drug for the protection of lymphocytes (i.e., AZT) was also investigated. C57BL/6 mice infected with the retroviral complex LP-BM5 were treated with GSH-loaded erythrocytes, GSH-loaded erythrocytes plus oral AZT, or GSH/AZTp2AZT-loaded erythrocytes plus oral AZT. The treatments including AZT and erythrocytes loaded with GSH alone or with GSH plus AZTp2AZT provided similar results and were most effective in inhibiting the progression of MAIDS; they reduced splenomegaly, lymphadenopathy, and hypergammaglobulinemia by about 70%, 90% and 83%, respectively, when compared with infected animals at 10 weeks postinfection. Evaluation of BM5d proviral DNA content in infected organs revealed that both treatments were able to almost completely protect most infected animals. They were also able to normalize the blood lymphocyte phenotype and to restore the responses of T and B cells to mitogens significantly. Treatment with GSH-loaded erythrocytes alone did not provide significant results for most parameters investigated, but a marked reduction in proviral DNA content was obtained in infected organs, including the brain. The results reported in this paper confirm the important role of macrophages in retroviral infection and moreover prove that erythrocytes, by selectively protecting these cells, strongly affect MAIDS progression. Furthermore, the combination of GSH- or GSH/AZTp2AZT-loaded erythrocytes with an oral nucleoside analogue (AZT) for the protection of lymphocytes provides additive responses in all the parameters investigated.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Peripheral blood lymphocytes (PBL) and CEM CD4+T-cell line can be infected by herpes simplex virus-1 (HSV-1). CEM cells were characterized as a cellular model to study interactions occurring between HSV-1 and HIV-1. Virtually all cells were persistently infected by HSV-1 (CEMHSV) and expressed the latency associated transcripts, whereas only a fraction tested positive for HSV-antigens. CD4 and CXCR-4 expression and function were not affected in CEMHSVcells and no significant increase of deoxyribonucleotide pools was noticed. Superinfection of CEMHSVcells with HIV-1 led to a cell line chronically infected by both viruses (CEMHIV/HSV). Evidence was also obtained that this cell line can produce HIV-1 pseudotyped by HSV-1 envelope. These results may have important implications for a better under-standing of AIDS pathogenesis.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Acute HIV-1 illness presents a wide range of clinical manifestations. We assessed a classification and data reduction of clinical features among 218 patients with acute HIV-1 infection enrolled in four prospective seroincidence studies. Factor analysis allows the definition of eight factors based on groups of symptoms and signs: gastrointestinal transit disturbances, weight loss/abdominal pain, lymphadenopathy, myalgia/arthralgia, neurologic features, constitutional and mucocutaneous features, oral candidiasis, and anorexia/pharyngitis. These groups reflected the main target systems involved at the time of acute HIV-1 disease. Grouping of symptoms and signs based on groups of patients is potentially more informative than observations made on individual patients. It might facilitate diagnosis, suggest pathogenic mechanisms and reduce the number of variables for characterizing acute HIV-1 illness.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Twenty-one women (propositi) who expressed serious concerns about changes in body habitus during highly active antiretroviral therapy (HAART) were evaluated by thorough physical examination, anthropometric measurements, and serum lipid and endocrine assays. The same evaluations were carried out in a comparison group of 21 women who received HAART but did not complain of changes in habitus. No significant demographic differences were found between the propositi and the comparison group, nor were there significant differences in CD4 count or plasma viral load (PVL) between the two groups. Lipid analyses were also performed on plasma obtained prior to HAART from 12 of the women. The frequency of changes reported by the 21 propositi were increase in abdominal size (90%), increase in breast size (71%), weight gain of >5 kg (43%), peripheral fat wasting (43%), buttock fat wasting (38%) and development of cervicodorsal fat pad (19%). A subset of patients in the comparison group experienced increase in abdominal size (29%) and weight gain >5 kg (19%), but none experienced clinically detectable peripheral or buttock fat wasting, increased breast size, or development of cervicodorsal fat pads. Mean waist circumference, waist-to-hip ratios (WHR), body fat, and body mass index (BMI) were above the desirable range for women in both propositi and the comparison group. Levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol associated with increased cardiovascular risk were found in 48%, 62%, 45%, and 33%, respectively, of the propositi, with similar findings in the comparison group. Fasting insulin levels were elevated in 4 propositi and 6 of the comparison group; mean insulin levels were within the normal range for both groups. In the comparison of lipids for the subset of patients before and after HAART therapy, HAART was associated with significant increases in total cholesterol, apolipoprotein B, and HDL cholesterol. Changes in body habitus caused by redistribution of fat occur commonly in women receiving HAART. Serum lipid abnormalities also are common during HAART and appear to be as frequent in women who do not experience clinically apparent body fat redistribution as in those who do. The observed changes in body fat distribution and in serum lipid levels are alterations that have been strongly correlated with increased risk for cardiovascular disease. Therefore, an understanding of the basis of these phenomena, and the risks with which they may be associated in this population, will be important for therapeutic decision making in women with HIV disease.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

In this cross-sectional survey conducted at the end of 1997 among the physicians of participants of the Swiss HIV Cohort Study (SHCS), 1487 of 2154 patients (69.0%) were treated with highly active antiretroviral treatment (HAART) defined as triple therapy with a combination of one or two reverse transcriptase inhibitors, and one or two protease inhibitors; 541 patients (25.1%) had never received such treatment. The physician's perception that the patient would not comply with treatment was one reason for not prescribing HAART to 20% of these patients (110). Physicians indicated that the most common reasons for the patient to refuse HAART were the fear of side effects (18%) and the patient's perception that treatment was too complicated (18%). Among 126 patients (5.8%) no longer receiving HAART, the most common reasons for discontinuing treatment were actual side effects (61%) or the fear of side effects (25%). Overall, 16% of patients did not receive therapy in accord with official Swiss guidelines. Multivariate logistic regression analysis indicated that patients with lower education, active intravenous drug users outside of a drug substitution program, and those who acquired HIV infection through intravenous drug use had a significantly higher risk of inadequate treatment. The physician's judgment of patient adherence and the physician's perception of the patient's fear of side effects are critical for the prescription of HAART. Physicians should address these issues to prevent unilateral withholding of treatment and increase the proportion of patients who may benefit from current antiretroviral therapy.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Risk factors for heterosexual HIV transmission are not fully understood. In fact, a proportion of people with sexual exposure to HIV remain uninfected despite multiple and continuous intercourse with HIV-infected partners. In this work, we have analyzed those virologic parameters potentially involved in the transmission of HIV through heterosexual contact. Thirty-eight couples with continuous unprotected sexual intercourse were included. HIV transmission occurred in 10 of 38 couples. No differences in clinical characteristics, exposure time, sexual practices, CD4 counts, or polymorphism in CCR5 were found between transmitter and nontransmitter groups. In contrast, virologic data were different between both groups; median values of viral load were 21.139 and 5.484 RNA copies/ml of plasma in the transmitter and nontransmitter groups, respectively, and a significant difference was found in mean viral load values (p= .03, Mann-Whitney test). Viral isolation was obtained in 90% of transmitters, but in only 44% of nontransmitter subjects (p= .02, Fisher's exact test). These data show that viral load levels and a positive viral isolation in culture must be considered as risk factors for heterosexual transmission of HIV-1.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background:If symptoms are to be recognized and effectively addressed in clinical research, they must be collected using sensitive, specific, reliable, and clinically meaningful methods.Objective:To perform a comparison of self-administered symptom survey data with data from conventional provider-reports.Design/Methods:Secondary data analysis of AIDS Clinical Trials Group Study 081 (ACTG 081), a randomized trial taking place in 33 sites comparing three approaches to prophylaxis forPneumocystis carinii-related pneumonia that found no difference among treatment arms. The study was performed on 842 subjects with advanced HIV infection. No intervention was undertaken as a result of this study. ACTG 081 included data on functional status, global quality of life and survival, and two methods of symptom measurement: an open-ended, provider-reported symptom assessment (provider-report) and a self-administered symptom survey (self-report). Agreement was measured using kappa scores. Sensitivity and specificity were calculated using self-report as the standard. Reliability was measured by intersite variation and test-retest reliability (8 weeks later). Clinical validity was evaluated by testing expected associations with functional status, global quality of life, and survival.Results:Symptom data were available for 808 patients (96%). Patient and provider agreement was poor (mean κ, 0.14; range, 0.07-0.25). Compared with self-report, providers underreported the presence and severity of symptoms (mean symptom count, 5.2 versus 1.3; mean severity score, 1.3 versus 0.74). provider-report demonstrated greater variability by site (R2associated with site, 0.02 versus 0.16) and poorer test-retest reliability (mean κ, 0.34 versus 0.25). Provider-report severity scores were less strongly associated than were self-report with functional status (χ2, 252 versus 80), global quality of life (R2for model, 0.57 versus 0.15), and survival (χ2, 38 versus 24). Self-reported symptom severity was strongly correlated to patient-reported global quality of life (ρ, 0.75;p< .0001).Conclusions:Provider-reported symptoms as currently collected within the ACTG are less sensitive and reproducible than a self-administered symptom survey. Provider-reported severity scores are also more weakly associated with functional status, global quality of life, and survival. A self-reported symptom survey may provide a better method of symptom measurement for HIV research.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:To examine and compare the validity of the HIV Dementia Scale (HDS) and Executive Interview (EXIT) in detecting HIV/AIDS dementia.Methods:The sample included hospitalized or skilled nursing/assisted-living facility (SNF) HIV/AIDS patients (N= 103). Participants completed the HDS, EXIT, and the Structured Clinical Interview from theDiagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV). A chart review also was performed.Results:Sample was predominantly male (93%) and white (79%), with a mean age of 38 years (standard deviation [SD] = 8 years). Twelve patients had a clinical diagnosis of HIV dementia. Cutoff scores of 10 or less for the HDS and 11 or more for the EXIT optimized sensitivity and specificity. Education level was related to performance for both tests. Using separate logistic regression analyses, the HDS and the EXIT were significant individual predictors of dementia. When entered together, the EXIT was the only significant predictor of dementia. Selected items of the HDS and EXIT also performed well in identifying patients with dementia.Conclusions:The HDS and the EXIT show promise as brief, well-tolerated screening tools for HIV dementia in ill patients. The HDS was more sensitive, but the EXIT added additional predictive power over the HDS in identifying dementia.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:To determine differences in rates of reactivity to purified protein derivative (PPD) tuberculin and of skin test anergy in relationship to serostatus, immune status, demographic characteristics, and other risk factors in women infected with or at high risk for infection with HIV-1; and to compare the usefulness of three different antigens in assessing delayed type hypersensitivity.Design/Methods:Cross-sectional analysis of baseline data in a multicenter prospective cohort study of 1343 HIV-1-seropositive and 390 seronegative but at-risk women recruited from sites of HIV primary care and through community-based outreach for a longitudinal cohort study.Results:4.7% of the 1343 HIV-1-seropositive women and 15.4% of the 390 HIV-seronegative women were tuberculin-positive (p< .001). A lower threshold in millimeters of induration for tuberculin reactivity among HIV-seropositive women resulted in a smaller difference between the seropositive and the seronegative groups. Even when a 2-mm threshold was used in HIV-seropositive respondents, with a 10-mm threshold among seronegative participants, the difference between the seropositive (6.9% reactive) and the seronegative (15.4% reactive) groups remained statistically significant (p< .001). Limiting analysis to women who responded to the non-PPD antigens did not eliminate the differences in PPD reactivity between the HIV-seropositive and HIV-seronegative women. In multivariate analysis, tuberculin reactivity was associated with HIV-negative serostatus, a history of tuberculosis infection or disease, geographic site, and CD4 count >200 cells/mm3in the HIV-seropositive women. In all, 41% of HIV-seropositive women and 12% of seronegative women were anergic (p< .001).Candidaantigen had the lowest response rates. In multivariate analyses, only HIV-serostatus and CD4 cell counts in HIV-seropositive women were significantly associated with anergy.Conclusions:In this community-based cohort of HIV-seropositive and HIV-seronegative women, we found significant differences between the seronegative and seropositive women even with a lower threshold of induration defining PPD reactivity among seropositive women and among women not anergic to the non-PPD antigens. Prevalence of PPD reactivity was higher than in previously described in cohorts of homosexual men, but lower than in cohorts of predominantly male injection drug users. Rates of anergy were similar to those in most previously described cohorts.

ISSN:1525-4135    

出版商:OVID    

年代:1999

数据来源: OVID