摘要:

Background:Lipodystrophies are rare cutaneous disorders characterized by the symmetrical loss of subcutaneous fat from the body surface. The cause of lipodystrophy is not known, but a possible genetic predisposition is likely and either overt diabetes mellitus or insulin resistance are often associated.Design and methods:Case study.Patients:Eight patients who developed either partial or generalized lipodystrophy after protease inhibitor therapy.Results:In all eight patients lipodystrophy occurred after 2–12 months of starting indinavir and was not preceded by weight loss or inflammatory skin disease. Short-term follow-up after withdrawal of therapy showed no change in the patients' appearance. One patient developed glycosuria as lipodystrophy became manifest. In three cases glucose tolerance test was performed revealing a high level of insulin between the first and third hour of loading.Conclusions:In our view, lipodystrophy is an unwanted side-effect of protease inhibitor therapy causing noticeable disfigurement.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To investigate whether members of a transfusion-linked cohort (the Sydney Bloodbank Cohort) infected with anef-deleted strain of HIV-1 could be differentiated from individuals infected with wild-type strains of HIV-1 by characterizing the Nef antibody response of cohort members.Design:Retrospective and prospective analysis of thenefgene sequence and the antibody response to Nef peptides in HIV-infected subjects.Methods:Plasma was obtained from all individuals of the Sydney cohort, and from a variety of HIV-1-infected and uninfected controls. Antibodies recognizing full-length recombinant HIV-1NL43Nef protein and synthetic peptide analogues were assessed by enzyme-linked immunosorbent assay.Results:All 34 individuals infected with wild-type HIV-1 had antibodies reacting with full-length Nef protein as well as with a series of synthetic peptides (6–23-mers) spanning most of the Nef protein of HIV-1NL43. Although the HIV-1 quasispecies infecting the Sydney cohort had a consensus deletion of thenefgene corresponding to amino-acids 165–206, HIV-1 strains from individual members of the cohort had additional deletions comprising up to 80% of thenefgene. Members of the cohort had antibodies to peptides homologous to all regions of the Nef protein tested, except for a single peptide (amino-acids 162–177) that lies within the consensusnefdeletion for the cohort quasispecies.Conclusion:These data show thatnef-deleted strains of HIV-1 can be detected serologically. In the Sydney cohort, detection of antibodies to all regions of Nef tested, except that corresponding to amino-acids 162–177, suggests that observed deletions outside this domain occurred after this virus had infected these subjects and stimulated an immune response. A Nef peptide serological assay may be useful for identifying further examples of individuals infected withnef-deleted, attenuated HIV-1 quasispecies and for assessing the evolution of those variantsin vivo.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:Characterization of the effects of infection with HIV-1 on cellular gene expression.Design and methods:Differential RNA display was applied to compare uninfected and HIV-1LAI-infected CEM cells 24 h post-inoculation. Differential bands were selected, cloned and several clones per band were sequenced. RNase protection assay was used to confirm differential display findings in HIV-1LAI-infected CEM cells as well as in another T-cell line (H9) infected with a different strain (HIV-1SF33).Results:Twelve differentially expressed bands, six up- and six downregulated in HIV-infected cells compared with controls, were selected. Four of the six upregulated bands were HIV transcripts. RNase protection assay of the remaining eight bands confirmed differential expression of four genes, including induction of a mariner transposase and moesin as well as suppression of α-nascent polypeptide-associated complex and mitochondrial heat shock protein 75 in HIV-1-infected cell cultures. Furthermore, a significant increase of glioma pathogenesis-related protein was found by RNase protection assay.Conclusions:Based on this initial limited differential display analysis, it was estimated that expression of 3% of the host genes was altered by HIV-1. Amongst the identified gene modifications, the induction of a mariner transposase may alter cellular gene expression itself, whilst the enhanced expression of glioma pathogenesis-related protein suggests a role in the host cell response to viral infection. The increase in moesin may facilitate viral budding and uptake. Furthermore, the suppression of α-nascent polypeptide-associated complex may promote translocation of HIV-1 polypeptides into the endoplasmic reticulum, whereas the downregulation of mitochondrial heat shock protein 75 may contribute to a cytopathic effect on mitochondria and possibly impairs antigen presentation.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To evaluate cross-clade recognition of p55 antigen by cytotoxic T lymphocytes (CTL) in persons infected with diverse clades of HIV-1; to facilitate the development of a CTL-inducing vaccine to prevent transmission of multiple clades of HIV-1.Design:Experiments were designed to evaluate whether persons in Uganda and the United Kingdom, infected with diverse clades of HIV-1, have CTL capable of recognizing and killing autologous target cells infected with recombinant vaccinia viruses (rVV) expressing the Gag protein from A, B, C and D clade HIV-1. The extent of cross-reactivity within such individuals, each infected with characterized virus, might reflect the type of cross-reactive immune response inducible by a monovalent vaccine.Methods:Asymptomatic HIV-positive individuals were fully tissue-typed by ARMS (amplification of refractory mutation system) polymerase chain reaction. rVV expressing the Gag protein from identified A, B, C and D viruses were prepared. CTL were cultured and tested for cytolytic activity on autologous rVV-infected or peptide-pulsed B cells.Results:Ugandan patients had inducible CTL responses recognizing A, B, C and D clade HIV-1 Gag. The majority of UK patients had inducible CTL responses that recognized two or more clades. No patient showed any HIV-2 cross-reactivity. Cross-reactive responses were characterized in three Ugandan patients.Conclusions:Most patients tested mounted cross-reactive CTL responses that recognized Gag proteins from clades of HIV-1 other than those with which they were infected.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To optimize the use of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for the evaluation of central nervous system (CNS) white-matter lesions that along with clinical findings and magnetic resonance imaging (MRI) can allow a definite diagnosis to be made; also to evaluate treatment with zidovudine plus foscarnet.Design and methods:Fifteen AIDS patients with uncertain CNS white-matter lesions were identified. HIV-1 RNA, cytomegalovirus (CMV) and JC virus (JCV) DNA were measured in a total of 29 CSF samples. The results were correlated with clinical and MRI findings and treatment with zidovudine plus foscarnet was evaluated.Results:Four and five out of 15 patients with CMV DNA ≥ 1 : 625 and JCV DNA ≥ 103copies/µl detected in the CSF were diagnosed with CMV and progressive multifocal leukoencephalopathy (PML), respectively. Six patients who were CMV/JCV-negative with the highest levels of HIV RNA (median, 6.87 log10copies/ml) in CSF were considered as having HIV-1 encephalitis. Neurological symptoms were non-supportive for diagnosis as was MRI in 11 out of 15 patients. Nine patients completed a 21-day course of zidovudine plus foscarnet. HIV RNA decreased irrespective of neurological diagnosis. All three HIV-1 encephalitis patients and two out of three patients with CMV leukoencephalopathy improved. In these two latter patients, relief of clinical symptoms coincided with decreased CMV DNA. JCV DNA remained unchanged and all three PML patients deteriorated.Conclusions:Measurement of CSF viral sequences supports the diagnosis of CNS white-matter lesions in AIDS patients. While effective therapy for PML remains elusive, treatment including zidovudine plus foscarnet may be a promising option for HIV-1 and CMV-related manifestations.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To describe the early manifestations of HIV-1 infection before the development of AIDS, in a rural Ugandan population.Methods:Three monthly follow-up of HIV-1-infected and uninfected participants in an HIV-1 natural history cohort from the start of the cohort in 1990 to the end of 1996.Results:A total of 107 persons with prevalent infection and 104 persons with incident infection were enrolled. Eighty (75%) prevalent and 89 (86%) incident individuals were asymptomatic on enrolment. Of the 91 persons with incident infection seen within 2 years of their estimated date of seroconversion, 51% [95% confidence interval (CI), 40–61] were still asymptomatic 2 years after seroconversion. At 4 and 5 years after seroconversion, only 26% (95% CI, 17–36) and 11% (95% CI, 4–22), respectively, remained asymptomatic. A total of 89 participants entered World Health Organization (WHO) stage 2, and their main stage-defining conditions were weight loss <10% (and > 5%) and minor mucocutaneous manifestations. The median CD4 lymphocyte count for participants entering WHO stage 2 was 516 × 106cells/l (interquartile range, 360–884 × 106/l). A total of 94 participants entered WHO stage 3 and the main reasons were weight loss >10%, unexplained chronic diarrhoea, fever for more than 1 month, and severe bacterial infection. The median CD4 lymphocyte count for participants entering WHO stage 3 was 428 × 106cells/l (interquartile range, 276–736 × 106/l). The rates of all conditions reported under the WHO staging system were significantly more frequent in HIV-positive persons than HIV-negative controls with the exception of fever for more than 1 month and oral hairy leukoplakia (which was seen in only three individuals).Conclusion:These are the first data from a non-selected African population describing the early manifestations of HIV infection. The main early manifestations were weight loss, minor mucocutaneous features, chronic diarrhoea, chronic fever and severe bacterial infections. The apparent rapid development of HIV-related signs and symptoms is probably indicative of the high background level of these conditions in our study area, as reflected by the rates of these conditions in the HIV-negative controls.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background:Pathogen-negative diarrhea is common in HIV infection and has been associated with clinical symptoms, histopathology, HIV expression, CD4+ lymphocyte depletion, cytokine mRNA expression, and apoptosis of lamina propria mononuclear cells.Objectives and methods:To examine the short-term (7-day) effects of treatment with combination antiretroviral therapies upon gastrointestinal symptoms and rectal mucosa in 15 HIV-infected subjects.Results:Treatment was associated with significant decreases in the perception of abdominal bloating and cramps. Similar declines in RNA burden and rises in CD4+ lymphocyte counts were found in blood and mucosa. Treatment was also associated with a fall in the number of lamina propria mononuclear cells undergoing apoptosis byin situlabeling, a change that correlated with the change in mucosal viral burden.Conclusions:Peripheral blood and mucosal compartments are equally responsive to effective antiretroviral therapies. The detection of significant changes within 7 days of starting antiviral therapy implies that intestinal dysfunction may be a direct result of local HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objectives:To determine whether recurrence of polymerase chain reaction (PCR) viraemia during maintenance ganciclovir for cytomegalovirus (CMV) retinitis correlates with (i) CMV disease at a new anatomical site, (ii) progression of the presenting retinitis, or (iii) acquisition of genetic changes in geneUL97associated with resistance to ganciclovir.Design:A previously described cohort of 45 patients presenting with first episode retinitis was followed clinically using ophthalmoscopy and serial tests for PCR viraemia for a median of 7 months. CMV viral load and genetic markers of ganciclovir resistance were measured in PCR-positive samples.Methods:PCR amplification of the glycoprotein B region of CMV and quantitative competitive PCR assays were employed. Genetic changes inUL97were identified by sequencing/point mutation assay.Results:PCR viraemia correlated significantly with new episodes of CMV disease (P= 0.011) and a trend was seen for the association with progression of retinitis (P= 0.07). Amongst the 14 patients PCR-positive during maintenance ganciclovir, 10 (71%) had genetic markers of resistance. None of these patients became PCR-negative in blood after reinduction ganciclovir therapy compared with three out of four without markers of resistance (P= 0.022).Conclusions:CMV PCR viraemia correlated strongly with the development of new episodes of CMV disease. Most patients with progression of retinitis remained PCR-negative in blood, consistent with therapeutic failure due to poor intraocular penetration of ganciclovir. However, the minority who were PCR-positive in blood may have reinfected their eye, and frequently had markers of ganciclovir resistance. The implications of these findings for the management of patients with CMV disease are discussed. © 1998 Lippincott-Raven Publishers

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Objective:To assess the effect of combination antiretroviral therapy including HIV protease inhibitors on the survival of patients with cytomegalovirus retinitis (CMVR).Design and participants:A longitudinal study of patients with CMVR diagnosed between October 1992 and May 1996 and followed to May 1997.Setting:UK National Health Service specialist HIV medicine department.Outcome measure:Time to death from first diagnosis of CMVR. Data were censored on 31 May 1997.Results:Data were available on 147 patients with CMVR. Median survival of CMVR patients before December 1995 was 256 days [95% confidence interval (CI), 197–315]. Following the introduction of protease inhibitors in December 1995 this rose to 555 days (95% CI, 351–759). By 31 May 1996 median survival for the entire group of patients alive with CMVR had risen to 720 days (95% CI, 551–889). The mean survival after CMVR diagnosis was 224 days (n = 89; 95% CI, 186–261; 1-year survival, 16%) in those who took no further antiretroviral therapy, 353 days in those who took nucleoside reverse transcriptase inhibitors but no protease inhibitors (n = 34; 95% CI, 289–418; 1-year survival, 50%), and 914 days in those who took a protease inhibitor (n = 24; 95% CI, 768–1059; 1-year survival, 83%;P< 0.0001). Multivariate analysis showed that the strongest independent predictor of improved survival was having ever received a protease inhibitor after CMVR (relative risk of death, 0.063; 95% CI, 0.027–0.149;P< 0.0001).Conclusions:The use of HIV protease inhibitors in combination antiretroviral therapy has been associated with a marked increase in the survival of patients with CMVR.

ISSN:0269-9370    

出版商:OVID    

年代:1998

数据来源: OVID