摘要:

Objective:To determine whether combination antiretroviral therapy is associated with reduced detection of HIV-1 RNA and DNA in the anorectal mucosa of men who have sex with men (MSM).Design:Cross-sectional study of 233 MSM recruited from community and clinic sites in Seattle, Washington between July 1996 and December 1997.Methods:HIV-1 RNA and HIV-1 DNA were detected in anorectal swab specimens by polymerase chain reaction amplification assays.Results:HIV-1 RNA was detected significantly less often in anorectal specimens from users of combination antiretroviral therapies, whether a protease inhibitor was received (15/89; 17%) or not (16/53; 30%), than in men not receiving therapy (43/88; 49%) (P < 0.001, P = 0.03, respectively). In contrast, HIV-1 DNA was detected only slightly less frequently in anorectal specimens obtained from men receiving protease inhibitors (35/81; 43%) or reverse transcriptase inhibitors alone (22/48; 46%) than in specimens from men not receiving therapy (45/78; 58%) (P = 0.07, P = 0.20, respectively). Among men with < 50 copies HIV-1 RNA/ml plasma, detection of HIV-1 RNA in anorectal specimens was rare (1/54; 2%) but detection of HIV-1 DNA was common (14/50; 28%).Conclusions:Combination antiretroviral therapy is associated with reductions in HIV-1 RNA, but HIV-1 DNA remains detectable in the anorectal canal of almost half of MSM receiving such therapy. Condom use during anal intercourse should be encouraged, regardless of plasma viral load response to potent antiretroviral therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objective:HIV-1 infection is associated with alterations of several vascular endothelial functions including adhesion molecule expression, growth, and vascular permeability. The bases of these errors are not known, but might involve secretion of the HIV-1 derived transcription factor `Tat-1'. This study investigated Tat-1 mediated endothelial barrier changes and second message regulation of this phenomenon.Methods:We exposed human umbilical vein endothelial cell monolayers to Tat-1 (0–150 ng/ml) for up to 48 h and measured resulting changes in monolayer permeability. We also investigated the role of tyrosine and mitogen activated protein (MAP) kinases, and protein kinase G using the pharmacological blockers genistein, PD98059 and KT5823 respectively.Results:Tat-1 significantly reduced monolayer barrier and increased albumin permeability within 24 h. Tat-1 also stimulated tyrosine phosphorylation of multiple endothelial proteins, disorganized junctional phosphotyrosine staining and increased the number of these immunostaining structures. The increased permeability produced by Tat-1 was blocked by genistein and PD98059, but not by KT5823. Genistein and PD98059 pretreatment also prevented the changes in phosphotyrosine immunostaining produced by Tat-1 and blocked phosphorylation of several proteins including MAP kinase.Conclusion:These results suggest that HIV may dysregulate endothelial barrier through the effects of Tat-1. These blocker experiments suggest that the effects of Tat are transcription/translation-dependent. These data demonstrate that Tat increases endothelial albumin permeabilityin vitrothrough tyrosine kinase and MAP kinase, but not protein kinase G pathways.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objectives:Several natural polymorphisms in the genes for the human CC-chemokine receptors CCR5 and CCR2 are associated with HIV-1 disease. TheCCR2-64Igenetic variant [a G to A substitution resulting in a valine (V) to isoleucine (I) change at position 64] is in strong linkage disequilibrium with a mutation within theCCR5regulatory region (CCR5-59653T). Individuals with two CCR2-64Ialleles are not resistant to sexual transmission of HIV-1, but progress significantly more slowly to HIV-1 disease. It is therefore important to determine the global distributions ofCCR2-64IandCCR5-59653Tgenetic variants and define the degree of linkage between them.Design and methods:We have developed molecular beacon-based, real-time PCR allele discrimination assays for all three chemokine receptor mutations, and used these spectral genotyping assays to genotype 3923 individuals from a globally distributed set of 53 populations.Results:CCR2-64IandCCR5-59653Tgenetic variants are found in almost all populations studied: their allele frequencies are greatest (∼35%) in Africa and Asia but decrease in Northern Europe. We confirm thatCCR2-64Iis in strong linkage disequilibrium withCCR5-59653T(96.92% of individuals had the same genotype for both CCR2-64IandCCR5-59653Tpolymorphisms).Conclusions:The greater geographical distribution of theCCR2-64I/CCR5-59653Thaplotype compared with that ofCCR5-Δ32suggests that it is a much older mutation whose origin predates the dispersal of modern humans.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objectives:To assess the characteristics of medication regimen modification and the influence of a commercial genotypic resistance assay on the short-term (3–12 weeks) viral load response (⩾ 0.5 log reduction) in HIV-1-infected patients extensively treated with antiretroviral therapy (ART).Methods:A nested cohort study was performed in two clinics from the HIV Outpatient Study of 96 persons with a HIV-1 viral load of 104 log copies/ml or greater taking at least two antiretroviral medications.Results:Successful modification was associated with adding at least two new medications [relative risk (RR), 1.5; 95% confidence interval (CI), 1.1–2.2], adding a drug from a previously unused class of agents (RR, 2.0; CI, 1.4–2.9), the initiation of a non-nucleoside reverse transcriptase inhibitor (NNRTI) (RR, 1.7; CI, 1.2–2.4), but not substituting a protease inhibitor or the use of a commercial genotypic resistance assay.Conclusion:Incorporating a drug from a previously unused class or changing at least two new medications, but, within the confines of this study, not using a commercial genotypic resistance assay, was associated with the successful modification of ART as measured by a reduction in viral load.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objective:To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment.Methods:The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points.Results:Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9–28.9] due to toxicity and 7.6% (95% CI, 4.9–10.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32–0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10–3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09–7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80–0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74–5.88 for log10copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06–0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04–1.26 versus hard-gell saquinavir).Conclusions:If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objectives:To evaluate tolerance for the oral administration of zidovudine (ZDV) during labor and measure the resulting ZDV concentrations in umbilical cord blood.Design:A cross-sectional study of women in a placebo-controlled trial of short-course ZDV (twice a day from 36 weeks' gestation until labor and every 3 h during labor) to prevent perinatal HIV transmission in Bangkok.Methods:Umbilical cord blood was collected. Sixty control specimens and specimens from 372 women (182 in the ZDV group, 190 in the placebo group) were tested for ZDV by radioimmunoassay (lower detection limit < 1 ng/ml).Results:All women in the ZDV group took one or more labor dose, 170 (93%) took their last dose within 3 h of delivery, and only five (3%) experienced nausea or vomiting, a proportion similar to the placebo group. The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml (range, < 1–1133 ng/ml); 31 (17%) specimens were less than 130 ng/ml (0.5 μM), the concentration thought to be active against HIVin vitro. Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses, 290 ng/ml in those taking three or four doses, and 293 ng/ml in those taking more than four doses (P < 0.01). The ZDV concentration was not associated with time since the last dose, body weight, or perinatal transmission.Conclusion:Oral intrapartum ZDV was feasible and well tolerated. Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration. Although concentrations were not associated with perinatal transmission, these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objective:To evaluate the efficacy and safety of the foscarnet–ganciclovir combination in induction therapy (IT) and maintenance therapy (MT) for cytomegalovirus (CMV) central neurological disorders in HIV-infected patients.Design:An open pilot non-comparative multicentre study.Methods:Thirty-one patients with acute CMV encephalitis (CMVe) (n = 17) or CMV myelitis (CMVm) (n = 14) during the era before highly active antiretroviral therapy (HAART) received intravenous IT with foscarnet 90 mg/kg plus ganciclovir 5 mg/kg twice a day followed by MT. The primary endpoint was clinical efficacy, assessed at the end of the induction phase.Results:The foscarnet–ganciclovir combination in IT resulted in a 74% (23 out of 31 patients) clinical improvement or stabilization. Eight patients did not respond clinically. Side-effects leading to drug discontinuation occurred in 10 patients during IT. Among the 23 patients who qualified for the maintenance phase, CMV disease progressed in 10, with a median time to the first relapse of 126 days (range 64–264 days). Overall, the median survival time was 3 months [95% confidence interval (CI), 2–4 months].Conclusion:The combination of foscarnet and ganciclovir can safely be used for CMV central nervous system (CNS) infection, with an improvement or stabilization in 74% of patients. Life-long MT with this combination is recommended as long as the immune system is profoundly impaired.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objective:To determine the tuberculosis (TB) transmission patterns within the prison system in Catalonia, conventional epidemiological techniques were combined with DNA fingerprinting ofMycobacterium tuberculosis.Methods:IS6110- and polymorphic GC-rich repeat sequence (PGRS)-based restriction fragment length polymorphism (RFLP) were combined with epidemiological studies to assess the relatedness of isolates from all patients with confirmed TB at five prisons in the province of Barcelona (Catalonia, Spain), between 1 July 1994 and 31 December 1996. Risk factors for transmission were analysed to a logistic regression. The extent of drug-resistant TB was also assessed.Results:The incidence of TB during the study period was 2775 cases per 100 000 inmate years. Of the 247 culture-positive cases, 126 (51%) appeared to have active TB as a result of recent transmission. Using conventional epidemiological methods, 14 active chains of transmission were identified in prison involving 65 isolates (52% of clustered patients). A lengthy history of imprisonment [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.52–5.11] and pulmonary TB (OR 2.36, 95% CI 1.17–4.75) were independently associated with clustering. Low rates of both initial (2.9%) and acquired drug resistance (5.8%) were identified and there was no evidence of the transmission of drug-resistant TB.Conclusion:In the prison system studied, the recent transmission of TB contributes substantially to the overall incidence of the disease. Both lengthy incarcerations and delays in identifying inmates with pulmonary symptoms play a key role in this recent transmission. Directly observed therapy (DOT) is a critical control strategy for reducing the emergence of drug resistance and for avoiding the transmission of resistant organisms.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objectives:To examine the association between type of sexual partnership and condom use consistency.Design:A prospective follow-up study of women attending two urban clinics for sexually transmitted diseases (STD).Methods:Sexual diaries recording barrier method, partner initials and partner type for each act of intercourse were kept by 869 women. Condom use by partner type was evaluated in three ways in the entire group: among women who encountered multiple partners, during months in which women encountered multiple partners, and within sexual partnerships that changed status during the study.Results:Consistency of condom use was higher with new and casual partners than with regular partners in the entire group and among women who encountered multiple partners. In months in which partners of different types were encountered, condom-use consistency was higher with new and casual partners than with regular partners. Consistent condom use decreased in partnerships that changed status from new to regular. The female condom was used more often with regular partners than with new or casual partners in the entire study group, among women who encountered multiple partners, and during months in which a woman achieved consistent use with her regular partner.Conclusions:This study provides strong evidence that condom use behavior is modified by partner type. Observations about condom use and partner type made in cross-sectional or retrospective surveys also hold in the present longitudinal analyses of individual women and of partnerships that change status. The female condom may be an important option for achieving consistent protection within stable partnerships.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objective:To examine the characteristics of repeat and first-time HIV testers and consider their implications for HIV test counselling.Methods:An anonymous questionnaire was completed by nearly 1500 people seeking an HIV test between September 1997 and July 1998 at a same-day HIV testing clinic in London, United Kingdom. Repeat testers were those people who had previously tested HIV negative and were returning for another test. Information was collected on self-reported unprotected penetrative sex (UPS) in the previous 3 months and reasons for seeking the present test.Results:Overall, 50.6% (721/1446) of all clinic attenders were repeat testers: gay men 71.7% (337/470), heterosexual men 42.1% (208/494) and heterosexual women 38.6% (186/482). No significant differences were found between repeat and first time testers in the frequency of UPS (P ⩾ 0.06). However, gay men (butnotheterosexual men and women) reporting three or more previous HIV tests were significantly more likely to report higher-risk UPS (i.e. with a partner whose HIV status was either positive or unknown) (42.2%) than those who had had one–two or no previous tests (25.3 and 25.4%, respectively;P = 0.002). Over half the heterosexual men and women, and one third of gay men said they were seeking the current HIV test in preparation for a new relationship; these proportions did not differ significantly between repeat and first-time testers (P > 0.1).Conclusion:In this London HIV testing clinic, no significant differences were found in the frequency of UPS between repeat and first-time testers with the exception of gay men with a history of three or more previous HIV tests, who reported elevated levels of high-risk sexual behaviour. For many people, repeat HIV testing has become part of a risk reduction strategy to establish seroconcordance with a regular partner. HIV test counselling provides the opportunity both to address high-risk behaviour and to reinforce personal risk-reduction strategies

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID