ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To analyse the HIV‐1‐specific cytotoxic T‐lymphocyte (CTL) responses of nine HIV‐seropositive subjects in relation with primary infection.Methods:Anti‐HIV CTL were generated byin vitrostimulation of peripheral mononuclear cells obtained from HIV‐seropositive donors at various times after primary infection. They were tested against several structural or regulatory HIV‐1 proteins, using autologous target cells infected with recombinant vaccinia viruses expressing one of the HIV‐1LAIproteins.Results:An important CTL activity was found during the first month following seroconversion only in those donors who showed clinical symptoms during primary infection. The temporal evolution of this response differed for each subject; one remained a non‐responder even 30 months after seroconversion. The structural proteins were recognized particularly early, while the antigenicity of regulatory proteins appeared later.Conclusion:Different patterns of HIV‐specific CTL response can be observed after primary infection. The evolution of infection in these different HIV‐seropositive subjects will be particularly interesting to analyse.AIDS 1995,9:421‐426

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To investigate the role of maternal HIV‐1 isolate phenotype and a child's cell susceptibility/resistance to viral infection in mother‐to‐child HIV‐1 transmission.Patients and methods:Forty‐nine women were studied at the time of delivery. Primary isolates, obtained by culturing patient peripheral blood mononuclear cells (PBMC) with PBMC from healthy donors, were characterized for tropism and syncytium‐inducing capability in monocyte‐derived macrophages (MDM), peripheral blood lymphocytes (PBL), and in the MT‐2 and MOLT‐3 T‐cell lines.Results:Seven women transmitted HIV‐1 to their children. Primary isolates were obtained from six and 28 transmitting and non‐transmitting mothers, respectively. All primary isolates from transmitting mothers and their infants but only 50% of those from non‐transmitting mothers replicated in MDM, regardless of their replication capacity in T‐cell lines. PBL and MDM cells from six uninfected children were exposed to the corresponding maternal isolates. Polymerase chain reaction analysis of HIV‐1 DNA in cells and p24 antigen assay in culture supernatants disclosed that two PBL and five MDM cultures were resistant to viral infection; two other PBL cultures, although HIV‐1‐infected, were negative for p24 production. Depletion of CD8+ cells only partially restored productive infection in CD4+ cell cultures. Moreover, all six PBL but only one MDM cultures were productively infected by an isolate obtained from a transmitting mother, thus suggesting that MDM resistance to HIV‐1 infection is not viral isolate‐restricted.Conclusions:Our findings strongly suggest that mother‐to‐child HIV‐1 transmission is influenced by both monocyte‐macrophage tropism of the maternal isolate and susceptibility of the child's target cells, in particular monocyte‐macrophages, to HIV‐1 infection.AIDS 1995,9:427‐434

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To investigate genotypes and serotypes of HIV‐1 variants in Russia, Byelorussia and Lithuania.Patients and methods:Sera from 20 HIV‐1‐infected individuals were tested in an enzyme‐linked immunosorbent assay (ELISA) with 19 V3 synthetic peptides, and serum HIV‐1 V3 RNA was amplified and sequenced.Results:Sequence comparison of the envelope V3 region among specimens tested revealed a 2‐29% range of nucleotide divergence, with a mean of 19%. Phylogenetic analysis clustered the V3 sequences recovered with subtypes A, B, C, D and G. All sequences from the homosexual men were shown to belong to subtype B, and all of the heterosexually infected individuals to subtype C. Sequences from the parenterally infected individuals were more heterogeneous. In the peptide ELISA three reactivity patterns were found. Serum samples from six out of seven homosexual men showed reactivity to peptides p108 or p110 representing V3 amino‐acid sequences found in US/West European HIV‐1 isolates. Serum samples from six out of seven individuals who had acquired HIV‐1 through heterosexual contacts were reactive to peptide p169. Four out of six parenterally infected patients had peak reactivity to p168.Conclusion:Distinct HIV‐1 variants were found in Russia, Byelorussia and Lithuania, which were introduced simultaneously in the mid‐1980s. This diversity was shown to be associated with the route of transmission. Homosexual men appeared to be infected with subtype B and heterosexually infected individuals with subtype C HIV‐1 variants. HIV‐1 subtypes A, C, D and G were found among parenterally infected individuals.AIDS 1995,9:435‐439

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To establish the role of prostaglandin E2(PGE2) formed and released by monocytes and monocyte‐derived macrophages (MDM) in the reduced toxoplasmastatic activity of these cells.Design:Determination of PGE2levels in the serum of AIDS patients, the release of PGE2by monocytes and MDM from AIDS patients, the toxoplasmastatic activity of these cells and the effect of indomethacin, an inhibitor of PGE2synthesis, on this cell function.Setting:Laboratory of Cellular Immunology of the Department of Infectious Diseases, University Hospital, Leiden.Participants:Twenty‐six AIDS patients. Healthy blood donors served as controls.Results:The concentration of PGE2in the serum from AIDS patients was significantly higher compared with serum from controls. Non‐stimulated monocytes and lipopolysaccharide‐stimulated monocytes and MDM from AIDS patients released significantly more PGE2than corresponding cells from the controls. The proliferation ofToxoplasma gondiiin monocytes and MDM from AIDS patients was significantly higher than in the respective cells from controls. Preincubation of these cells with indomethacin resulted in a decreased proliferation ofT. gondiiin non‐activated monocytes and MDM and in interferon‐&ggr;‐activated MDM from AIDS patients. Preincubation of monocytes from healthy donors with PGE2resulted in a dose‐dependent increase ofToxoplasmaproliferation which confirms that PGE2can reduce the toxoplasmastatic activity of monocytes.Conclusion:PGE2is involved in the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients.AIDS 1995,9:441‐445

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To determine if cultured feline Kupffer cells (KC) are as permissive for feline immunodeficiency virus (FIV) as cultured human liver macrophages are for HIV. Two types of infection likely to be relevant to thein vivosituation were used. KC were infected with either free virus or autologous infected peripheral blood mononuclear cells (PBMC).Methods:Feline KC were isolated by centrifugal elutriation from collagenase‐perfused liver; cultured cells were characterized by their morphological appearance and their erythrophagocytotic properties. After infection, viral replication was measured by enzyme‐linked immunosorbent assay, reverse transcriptase activity, immunofluorescence assay,in situhybridization and electron microscopic observations.Results:Three days after isolation, 85% of cultured KC were able to internalize red blood cells; 45% were CD4‐positive and 65% expressed a 24kD protein thought to be a receptor for FIV (CD9). After the addition of autologous infected PBMC or cell‐free supernatant of chronically infected IRC4 cells to KC cultures, a peak of viral replication was detected at day 28. Antigen revealed by immunofluorescence assay was present in only 0.4%, and viral RNA was detected byin situhybridization in 2% of the infected cells.Conclusions:FIV can replicate in cultured feline KC without inducing any cytopathic effect, which suggests that these cells may play a role in the physiopathology of FIV infection.AIDS 1995,9:447‐453

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:To investigate the timing of onset of each clinical sign in infants and children with HIV‐1 perinatal infection.Design and methods:A total of 200 HIV‐1‐infected children followed‐up from birth were studied. Failure and conditional probabilities were estimated by the Kaplan‐Meier product‐limit method. Cox proportional hazard analysis was used to evaluate independently associated factors. Results of 934 seroreverters were used to calculate reference values of CD4+ cell counts and predictivity of early signs.Results:Median age at the onset of any sign was 5.2 months (range, 0.03‐56 months). The probability of remaining asymptomatic was 19% [95% confidence interval (CI), 14‐25.1] at 12 months and 6.1% (95% Cl, 2.6‐11.7) at 5 years. Lymphadenopathy (69.5%), splenomegaly (62.4%) and hepatomegaly (58.4%) were the most common signs in the first year of life. Peculiar to the first year of life (compared with subsequent ages) was the onset of primary HIV‐1 hepatitis and diarrhoea (rate ratios, 23.3 and 15.2, respectively). When CD4+ cell counts in the asymptomatic stage (age, 2 months; range, 0.03‐5.9 months) were below rather than above the fifth percentile in seroreverters, onset of signs was earlier [3 (range, 0.03‐19) versus 5 (range, 0.03‐56) months]. Children manifesting signs before the 5.2‐month breakpoint had a lower survival rate [74% (range, 65.9‐82%) at 12 months and 45% (range, 32.9‐57%) at 5 years] than children manifesting signs later 198% (range, 92.2‐100%) at 12 months and 74% (range, 60.3‐87.7%) at 5 years]. Children whose birthweight was ≤2400g had an earlier onset (24 months; range, 1‐57 months) of severe conditions than children with higher birthweight (71 months; range, 1‐71 months). Development of lymphadenopathy or hepatosplenomegaly within 3 months of life were reliable indicators of infection.Conclusions:This study describes the sequence of onset of signs in perinatal HIV‐1 infection. Infection is shown to progress faster than in adults and in a different manner. Low birthweight, early decreased CD4+ cell counts, and early onset of signs are predictive of rapid progression.AIDS 1995,9:455‐461

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective:Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddl; 2′,3′‐dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated.Design:A total of 426 patients with AIDS or AIDS‐related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts ≤ 150 × 106/l were randomized to receive either a high (750 mg for bodyweight ≥ 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 1 34 mg, respectively) dose of ddl daily.Setting:The patients were recruited from 31 German and Austrian AIDS clinical primary‐care centres.Results:The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92;P= 0.003) and neuropathy (28 versus 43; relative risk, 1.55;P= 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient‐years) versus 84 (44.4 per 100 patient‐years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient).Conclusions:This study cannot conclude on ddl efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddl therapy is considered, daily doses < 750 mg should be administered.AIDS 1995,9:463‐469

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objectives:To evaluate the efficacy and safety of oral ganciclovir for the maintenance treatment of cytomegalovirus (CMV) retinitis in patients with AIDS.Design:A 20‐week, randomized, multicentre, open‐label study. Progression of retinitis was assessed by funduscopy and masked reading of fundus photographs.Methods:Adult patients with AIDS and stable CMV retinitis following a 2‐3‐week induction course of intravenous ganciclovir (5 mg/kg every 12 h) were randomized 2:1 to receive maintenance therapy with oral ganciclovir 500 mg six times daily, or 5 mg/kg intravenous ganciclovir once daily infused over 1 h. The primary efficacy variable was time to progression of CMV retinitis from initiation of maintenance therapy.Results:A total of 159 patients were enrolled; 112 received oral ganciclovir and 47 intravenous ganciclovir. By masked assessment of fundus photographs, CMV retinitis progressed in 72% of patients in the oral group and 76% in the intravenous group. Mean time to progression was 51 days with oral ganciclovir and 62 days with intravenous ganciclovir (P= 0.15). By funduscopy, CMV retinitis progressed in 59% of oral ganciclovir patients and 43% of intravenous ganciclovir patients. Mean time to progression was 86 and 109 days, respectively (P= 0.02). Diarrhoea and neutropenia (absolute neutrophil count < 500 × 106/I) were the most frequently reported adverse events in both groups. The incidence of sepsis for the oral and intravenous ganciclovir patients was 3 and 8.5%, respectively. Infection at the intravenous site occurred in 0 and 9% of patients, respectively.Conclusions:Oral ganciclovir offers an effective and safe alternative to intravenous ganciclovir in the maintenance therapy of CMV retinitis.AIDS 1995,9:471‐477

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objectives:The aim of this study was to identify and critically review behavioural interventions in the HIV prevention and sexual health fields.Methods:Electronic and hand searches were conducted to retrieve relevant published and unpublished reports of outcome evaluations. A methodological review was carried out to identify those with sufficient methodological strengths to generate reliable conclusions as to effectiveness. Soundly designed studies were defined as those which met the four core criteria of employing control groups, providing pre‐ and post‐intervention data and reporting on all targeted outcomes.Results:A total of 68 separate reports of outcome evaluations were located. Only 18 were judged to be methodologically adequate. Major problems found were lack of a control group or non‐equivalent/unbalanced control groups, small sample sizes, failures to report pre‐intervention measures, short follow‐up, and high attrition rates. Academic reviewers were more likely than the authors of papers to judge reports of evaluations as providing insufficient information to assess effectiveness.Conclusion:Evaluation design in this field needs to be improved. Recommendations include more use of randomized controlled trials and the raising of publication standards by journals.AIDS 1995,9:479‐486

ISSN:0269-9370    

出版商:OVID    

年代:1995

数据来源: OVID