摘要:

Objective:To ascertain the prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, and cytomegalovirus (CMV) DNA in semen was investigated.Methods:Amplification by nested polymerase chain reaction was used to detect viral DNA sequences in samples from 24 HIV-infected gay men, 15 of them with Kaposi's sarcoma (KS), and 115 healthy donors.Results:Six of the 24 HIV-infected patients had detectable HHV-8 DNA in their semen: three of the 15 patients with KS and three of the nine patients without KS. CMV DNA was detected in 20 semen samples from HIV-infected patients. None of the semen samples from healthy donors had detectable HHV-8 DNA and rates of CMV DNA detection were low (3%).Conclusions:The study demonstrates the presence of HHV-8 in semen from HIV-infected individuals with, or at risk, of developing KS and the potential for sexual transmission of the virus. We found no evidence of HHV-8 in the semen of HIV-uninfected donors.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To determine whether the HIV-1 transactivator protein Tat acts as a DNA sequence-specific transcription factor and activates transcription from a heterologous TATAA element in the absence of thetrans-activation response (TAR) element and other sequences in the HIV-1 long terminal repeat (LTR).Design:Activating protein-1 (AP-1) and Tat-induced transcription were assessed using Jun and hybrid Tat/Jun-expression plasmids and reporter gene constructs which contained AP-1 binding sites upstream of the rat prolactin TATAA element or an HIV-1 LTR construct in which AP-1 binding sites replaced the TAR element.Methods:Tat-induced transcription was determined following transient transfection of colon epithelial cell lines with reporter gene constructs and Tat/Jun-expression plasmids in which Tat was fused to the DNA binding domain of Jun. Activation of prolactin (PL) and LTR reporter genes was assessed by luciferase (LUC) or chloramphenicol acetyltransferase (CAT) activity in cellular extracts.Results:Cotransfection of cells with Tat/Jun and the AP-1 PL LUC or LTR AP-1 CAT reporter plasmid resulted in a marked increase in reporter gene activity which was comparable with that induced by transfection of cells with several different AP-1 expression plasmids (e.g., JunD, JunB, c-Fos), or that elicited by stimulation of the cells transfected with LTR AP-1 CAT plasmids with phorbol ester or tumor necrosis factor-α. Tat-induced transcription was DNA-mediated since both a Jun DNA binding domain fused to Tat as well as AP-1 binding sites within the promoter were required for the induction of CAT expression.Conclusions:Tat-activated transcription can occur strictly through a heterologous TATAA element independent of TAR and Sp1 binding sites or other HIV-1 LTR sequences. Tat appears to increase transcription initiated through the TATAA element by mechanisms similar to that of DNA sequence-specific transcription factors.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To analyse the effect of HIV-1 infection on the glucose metabolism of human intestinal epithelial cells.Methods:HT-29 cells were infected with HIV-1NDKand studied 3 weeks (acutely infected cells) or 9 months (chronically infected cells) post-infection. Perchloric acid extracts were analysed by high-resolution1H,31P and13C nuclear magnetic resonance spectroscopy. Metabolite concentrations and specific13C enrichments were quantified for chronically infected, acutely infected and control cells grown in Dulbecco's modified Eagle's medium containing natural-abundance or 1-13C-enriched glucose to determine significant differences between infected and non-infected cells.Results:Chronically HIV-infected cells showed alterations in glycerol-3-phosphate (+40%), fructose-1,6-diphosphate (−66%), uridine diphosphate glucuronic acid (−33%), lactate (+75%) and [1-13C]glucose (+181%) levels, and in specific lactate 3-13C enrichment (+19%) when compared with controls. Acutely infected cells exhibited decreased fructose-1,6-diphosphate (−58%) and increased nicotinamide adenine dinucleotide (+33%) levels relative to controls.Conclusion:HIV-1 infection results in a disturbance of glycolytic and oxidative activities in human intestinal epithelial cells. This finding supports the concept that HIV-1 may directly impair some metabolic functions of the intestinal epithelium, and that it can be considered a potential aetiological agent for HIV-associated enteropathy.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To study the possibilities and limitations of postexposure treatment to prevent the establishment of infection after accidental exposure to HIV.Design and methods:The effect of 2′,3′-dideoxy-3′-hydroxymethyl cytidine (BEA-005) was investigated on acute simian immunodeficiency virus (SIV) and HIV-2 infections in macaques in pre- and postexposure treatment experiments.Results:Postexposure treatment with BEA-005 (3 x 10 mg/kg) for as short as 3 days prevented infection with SIVsmafter intravenous or rectal inoculation. Infection with HIV-2 could also be blocked by postexposure BEA-005 treatment.Conclusion:This study shows that therapeutic intervention can block early systemic and mucosal infections with SIV and HIV-2. Further evaluation is ongoing.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:This study assessed the ability ofin vitrosusceptibility testing of clinical Candidaisolates to predictin vivoresponse to itraconazole cyclodextrin solution.Methods:One hundred specimens were obtained from HIV-positive patients with oral thrush, of which 72 speciments were from patients who were clinically unresponsive to fluconazole at standard doses and had fluconazole-resistant isolatesin vitro. Susceptibility to itraconazole was assessed by measuring the relative growth of an isolate in liquid medium containing a single concentration of itraconazole and then expressing growth in itraconazole as a percentage of growth in antifungal-free medium.Results and conclusions:Where specimens yielded only one isolate, a cut-off relative growth in itraconazole of 68% discriminated between isolates from patients failing to respond clinically to itraconazole solution and those from patients successfully treated with the preparation (specificity 100%; sensitivity 88%). The presence of mixed infection reduced the predictive accuracy of the test. Only 30% of fluconazole-resistant isolates were cross-resistant to itraconazole. No isolates were resistant to itraconazole but susceptible to fluconazole. Non-response to itraconazole solution was attributed to resistant yeast infection in the majority of cases, and this susceptibility method accurately identified specimens from patients unlikely to respond to the drug.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:To investigate whether apparently beneficial changes in plasma HIV RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are associated with a corresponding clinical benefit.Methods:For 620 patients in two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV) plasma HIV RNA and CD4 lymphocyte count changes were compared in patients randomized to 3TC plus ZDV and patients randomized to other treatment arms. The effect of therapy on the HIV RNA level and CD4 count was compared with the effect of therapy on clinical endpoints over the same time period.Results:Median baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 × 106/l for CD4 count. During the trial a significantly lower HIV RNA level and higher CD4 count was sustained in the ZDV/3TC group compared with the other group, with a difference in the median area under the curve from baseline per month of follow-up of 0.38 log10copies/ml HIV RNA and 0.18 log2× 106/l CD4 cells (P< 0.001 in each case). For patients who were initially asymptomatic or in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4 count was 3.14 [95% confidence interval (CI), 1.44–6.83] and for a 10-fold higher HIV RNA level was 3.22 (1.20–8.59). The RH of progression to AIDS expected with ZDV/3TC compared with the control treatments, given the observed effects of treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed value was 0.16 (0.03–0.74). After adjustment for HIV RNA and CD4 changes over time the observed RH of progression to AIDS for ZDV/3TC treatment compared with controls was increased to 0.36 and was no longer significant (95% CI, 0.07–1.85).Conclusion:In this analysis of two trials, the effects of ZDV/3TC in reducing plasma HIV RNA and raising peripheral blood CD4 counts were associated with concurrent clinical benefits and the effect of treatment on these markers could account for at least part of the clinical benefits of therapy that were observed.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To define the factors associated with diagnosis of toxoplasmic encephalitis (TE) in AIDS patients; and to establish a rational procedure for the clinician faced with a decision concerning empiric antitoxoplasma therapy.Design:A 15-month prospective multicentre cohort study in France.Methods:One hundred and eighty-six consecutive HIV-positive inpatients undergoing empiric antitoxoplasma therapy for a first episode of presumed TE were monitored. The clinician's initial estimation of the probability of response to antitoxoplasma therapy was recorded. In addition, a validation committee classified cases as TE or non-TE.Results:Among the 186 patients, the following variables were significantly more frequent in TE (n = 113) than non-TE (n = 73) patients: fever (59% versus 40%), headache (55% versus 33%), seizures (22% versus 11%), suggestive lesions on the brain scan (98% versus 76%), positive Toxoplasma serology (97% versus 71%). Median CD4+ lymphocyte count was significantly higher in TE than in non-TE (27 x 106/l versus 11 x 106/l). The rate of TE in patients on systemic antiprotozoal prophylaxis at entry was 43% as compared with 75% in patients without previous prophylaxis. Pre-therapy estimation of response to empiric therapy was highly correlated with final diagnosis. Multivariate logistic regression analysis showed that the following variables contributed independently to the diagnosis of TE: clinician's estimation of response to treatment at entry > 75%; absence of systemic antiprotozoal prophylaxis; seizures; headache; suggestive lesions on CT or MRI brain scan; and positive Toxoplasmaserology.Conclusions:A linear logistic model is proposed which uses significant variables, which are readily available. This model gives good accuracy to classify suspected cases of TE.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:A severe dose-limiting axonal peripheral neuropathy may develop in subjects on treatment with the nucleoside analogues didanosine (ddI), zalcitabine (ddC), and stavudine (d4T). The impairment of mitrochondrial DNA synthesis is crucial to the pathogenesis of this disorder although other mechanisms have not been ruled out. The depletion of acetyl-carnitine, which regulates the metabolism and function of peripheral nerves, could contribute to the neurotoxicity of these compounds.Design:Non-randomized, cross-sectional study of selected patients.Methods:We measured the serum levels of acetyl- and total carnitine in 12 subjects with axonal peripheral neuropathy developed on treatment with different regimens of neurotoxic nucleoside analogues (ddI, ddC, d4T). Subjects who did not develop peripheral neuropathy while staying on treatment with ddI (n = 10) or zidovudine (n = 11) served as the control groups. HIV-negative subjects with axonal or demyelinating autoimmune neuropathies (n = 10) and healthy individuals (n = 13) were additional control groups.Results:Subjects experiencing axonal peripheral neuropathy on treatment with ddI, ddC and d4T had significantly reduced levels of acetyl-carnitine in comparison to the control groups. No difference was observed in the levels of total carnitine between study subjects and the control groups.Conclusions:Our results demonstrate that subjects who developed peripheral neuropathy while staying on treatment with ddI, ddC and d4T had acetyl-carnitine deficiency. The normal levels of total carnitine in the study group appear to indicate the specificity of the defect and rule out coexisting relevant nutritional problems. The critical role of acetyl-carnitine for the metabolism and function of the peripheral nerves supports the view that the acetyl-carnitine deficiency found in these subjects may contribute to the neurotoxicity of ddI, ddC and d4T, even though the interference with mitochondrial DNA synthesis is regarded as the main cause of their toxicity.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To test the safety of the ‘negotiated safety’ strategy — the strategy of dispensing with condoms within HIV-seronegative concordant regular sexual relationships under certain conditions.Method:Data from a recently recruited cohort of homosexually active men (Sydney Men and Sexual Health cohort, n = 1037) are used to revisit negotiated safety. The men were surveyed using a structured questionnaire and questions addressing their sexual relationships and practice, their own and their regular partner's serostatus, agreements entered into by the men concerning sexual practice within and outside their regular relationship, and contextual and demographic variables.Results:The findings indicate that a significant number of men used negotiated safety as an HIV prevention strategy. In the 6 months prior to interview, of the 181 men in seroconcordant HIV-negative regular relationships, 62% had engaged in unprotected anal intercourse within their relationship, and 91% (165 men) had not engaged in unprotected anal intercourse outside their relationship. Of these 165 men, 82% had negotiated agreements about sex outside their relationship. The safety of negotiation was dependent not only on seroconcordance but also on the presence of an agreement; 82% of the men who had not engaged in unprotected anal intercourse outside their regular relationship had entered into an agreement with their partner, whereas only 56% of those who had engaged in unprotected anal intercourse had an agreement. The safety of negotiation was also related to the nature of the safety agreement reached between the men and on the acceptability of condoms. Agreements between HIV-negative seroconcordant regular partners prohibiting anal intercourse with casual partners or any form of sex with a casual partner were typically complied with, and men who had such negotiated agreements were at low risk of HIV infection.Conclusions:The adoption of the strategy of negotiated safety among men in HIV-seronegative regular relationships may help such men sustain the safety of their sexual practice.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:The aim of this study was to document which genetic subtypes of HIV-1 have entered Sweden and to study transmission patterns of these virus variants.Patients:All HIV-1-infected individuals at Danderyds Hospital, Stockholm, Sweden, who were suspected of carrying a virus of African origin were prospectively included in the study. The study subjects originated from 15 different African countries.Methods:The V3 domain of the HIV-1 envelope was directly sequenced from uncultured peripheral blood mononuclear cells from 75 individuals included in the study. Phylogenetic analyses were used to determine genetic subtype and to study transmission patterns.Results:The virus strains carried by the study subjects belonged to six established subtypes of HIV-1 (27A, 4B, 18C, 18D, 2G, 2H). Two individuals from Zaire carried a subtype, which had not been classified previously, provisionally named subtype J. Eleven transmissions of non-subtype B strains in Sweden were documented.Conclusions:This study shows that most genetic HIV-1 subtypes have entered Sweden despite the relatively low prevalence of HIV infection in the country. Thus, the complete dominance of subtype-B infections which was seen during the early phase of the HIV-1 epidemic in Europe and the US has been broken in Sweden.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID