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ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:To compare the efficacy and safety of indinavir 800mg three times a day, ritonavir 600mg twice a day, and a combination of ritonavir 400mg twice a day and saquinavir 400mg twice a day, when administered with two nucleoside analogues.Design:A randomized, open-labelled, controlled trial. Two hundred and eighty-four patients started randomized treatment. The primary end-point was the proportion of patients with HIV RNA of 200 copies/ml or less (Roche Amplicor) and HIV RNA of 20 copies/ml or less (Roche ultradirect assay) at 6 months. Analysis was performed as intent-to-treat, and missing values were accounted for as failures.Results:As of 1 May 1998, 269 patients should have completed 24 weeks of treatment. The proportion of patients with HIV RNA of 200 copies/ml or less was 71% (indinavir), 67% (ritonavir), and 82% (ritonavir + saquinavir),P=0.07. In antiretroviral drug-naive patients (n=119), the corresponding figures were 63, 57, and 89% (P<0.01), whereas among drug-experienced patients (n=165) 77, 74, and 77% had HIV RNA of 200 copies/ml or less (P=0.90). The same pattern was observed in the ultradirect analysis. All three regimens were generally safe, but significantly more patients in the ritonavir group (37%) stopped treatment because of adverse drug reactions compared with the indinavir group (8%) and the ritonavir plus saquinavir group (16%) (P<0.001).Conclusions:Treatment with saquinavir plus ritonavir in combination with two nucleoside analogues is generally safe, and has superior short-term antiviral efficacy compared with indinavir and ritonavir also combined with two nucleoside analogues in antiretroviral drug-naive patients. Further follow-up is needed to determine the durability of the viral response.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:Most HIV-1 transmission is sexual; therefore, immune responses in the genital mucosa may be important in mediating protection against HIV infection. This study examined HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan female sex workers.Methods:HIV-1-specific immune responses were compared in HIV-1-resistant and HIV-1-infected sex workers, and in lower risk uninfected women. Cervical and vaginal samples from each group were tested for HIV-1-specific IgA and IgG by enzyme immunoassay. Systemic T-helper lymphocyte cell responses to HIV-1 envelope peptide epitopes were assayed using an interleukin 2 bioassay. HIV-1 risk-taking behaviours were assessed using standardized questionnaires.Results:HIV-1-specific IgA was present in the genital tract of 16 out of 21 (76%) HIV-1-resistant sex workers, five out of 19 (26%) infected women, and three out of 28 (11%) lower risk women (P< 0.0001). Among lower risk women, the presence of HIV-1-specific IgA was associated with HIV-1 risk-taking behaviour. Systemic T-helper lymphocyte responses to HIV-1 envelope peptides were present in 11 out of 20 (55%) HIV-1-resistant women, four out of 18 (22%) infected women, and one out of 25 (4%) lower risk women (P< 0.001). T-helper lymphocyte responses did not correlate with the presence or titre of virus-specific mucosal IgA in any study group.Conclusions:HIV-1-specific IgA is present in the genital tract of most HIV-1-resistant Kenyan sex workers, and of a minority of lower risk uninfected women, where it is associated with risk-taking behaviour. These data suggest a role for mucosal HIV-1-specific IgA responses in HIV-1 resistance, independent of host cellular responses.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:The role of HIV-1 antibody in modulating disease progression must be assessed in the context of other immune and viral load markers. We evaluated the association between HIV-1 p24 antibody, HIV-1 RNA, immune complex-dissociated (ICD) p24 antigen, CD4 cell percentage, and mortality in a cohort of 218 HIV-infected children enrolled in a trial of intravenous immunoglobulin prophylaxis of bacterial infections.Methods:CD4 cell percentage was measured and sera collected and stored at baseline and every 3 months on study (1988-1991). Stored sera were assayed for HIV-1 p24 antibody, HIV-1 RNA, and ICD p24 antigen. Mortality was recorded during the trial and updated through 1996 (mean total follow-up, 6.3 years).Results:Eighty-one (37%) children died; probability of mortality for children with baseline HIV-1 p24 antibody concentrations of undetectable (<1), 1-4, 5-124, and ≥125 reciprocal titer units (RTU) was 61, 50, 24, and 10%, respectively. A 3.5-fold increase in the relative risk (RR) of death [95% confidence interval (CI), 2.2-5.5] was observed among children with baseline HIV-1 p24 antibody concentration <5RTU compared with ≥5RTU. In multivariate analyses, p24 antibody, HIV-1 RNA, and CD4 cell percentage but not ICD p24 antigen were independently associated with mortality; the RR of death increased by 1.7 (95% CI, 1.3-2.1) for each log10decrement in baseline HIV-1 p24 antibody.Conclusions:HIV-1 p24 antibody, HIV-1 RNA and CD4 cell percentage independently predict mortality amongst infected children. Whereas CD4 cell percentage provides an estimate of the general degree of immune suppression, HIV-1 p24 antibody could provide an easily obtained, inexpensive assessment of CD4 cell function and could augment prognostic information provided by CD4 cell count and viral load for clinical management of infected children.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To analyse the genetic and phylogenetic characteristics of HIV-1 group O viruses.Materials and methods:Theenvgene, encoding the gp160 glycoprotein, and a partial p24-encodinggaggene fragment of a Cameroonian (CA9) and a Gabonese (VI686) HIV-1 group O virus, isolated from cultured peripheral blood mononuclear cells of symptomatic patients, were sequenced, aligned with other representatives of group O for which the same region has been documented, and genetically and phylogenetically analysed.Results:Phylogenetic analysis of theenvgene (gp160) revealed that CA9, VI686, ANT70, and four Ha strains formed a separate cluster, which was supported by 100% of all bootstrap trees. In addition, these seven isolates were part of the same clade in the p24 phylogeny. VAU and MVP5180 may represent two other subtypes.Conclusion:We have characterized two group O viruses, originating from Cameroon and Gabon, which show a close evolutionary relationship to ANT70 and four Ha strains based on the entireenvgene, suggestive of a first group O subgroup, tentatively named the HIV-1 group OenvANT70 clade or subtype.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To investigate the effect of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) and fluconazole on anti-cryptococcal activity of monocytes from AIDS patients and normal subjects.Design:The effect of GM-CSF and fluconazole on fungistatic and fungicidal activity of monocytes was studied in anin vitrosystem.Methods:Monocytes were treatedin vitrowith hrGM-CSF and fluconazole or either agent alone for 24 or 48h, and fungistatic and fungicidal activity was evaluated in a colony-forming unit inhibition assay. CD11b/CD18 expression in monocytes was measured by flow cytometry analysis. Superoxide anion generation by peripheral blood monocytes was measured in the presence of pre-opsonized zymosan.Results:Defective antifungal capacity of monocytes from AIDS patients was observed. GM-CSF treatment of monocytes from AIDS patients increased fungistatic activity, and the combination of hrGM-CSF and fluconazole resulted in fungicidal activity. The mechanisms involved in the GM-CSF-mediated effect appeared to be mediated by (i) enhancement of phagocytic activity, (ii) increase of superoxide anion generation, and (iii) upregulation of CD11b/CD18 expression on the monocyte surface.Conclusions:Our data highlight the effect of GM-CSF on anti-cryptococcal activity of human monocytes and show a synergistic effect of GM-CSF with fluconazole, suggesting a new therapeutic strategy in the treatment of cryptococcosis.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To assess changes in HIV RNA and their relationship to disease progression.Design and setting:Delta was a randomized double-blind trial comparing zidovudine (ZDV) monotherapy with ZDV plus didanosine (ddI) or ZDV plus zalcitabine (ddC). Participants had AIDS (with CD4 cell counts above 50×106/l), AIDS-related complex, or were asymptomatic with CD4 cell counts below 350×106/l. The trial included both ZDV-naive and ZDV-experienced participants.Participants:A total of 1280 participants in the Delta trial whose serum samples had been stored at -70°C and who had a minimum of one sample taken before the start of treatment and at least one later sample.Methods:HIV-1 RNA quantification was performed using the nucleic acid sequence-based amplification HIV-1 RNA quantitative assay with a cut-off of 800 copies/ml.Results:Reductions in HIV RNA by treatment group were consistent with theclinical results; in ZDV-naive participants the maximum median fall occurred at 4 weeks for all three groups (ZDV, 0.54log10copies/ml; ZDV-ddI, 1.38log10copies/ml; ZDV-ddC, 1.31log10copies/ml). On average the reductions were smaller in ZDV-experienced participants but the difference between the monotherapy and combination arms was very similar in ZDV-naive and experienced participants. Baseline HIV RNA levels, adjusted for CD4 cell counts were highly predictive of time to virological response (HIV RNA <800 copies/ml); HIV RNA nadirs achieved were predictive of survival. Viral load rebound following response was independent of treatment group and previous ZDV therapy.Conclusions:Virological changes in response to treatment are of value in assessing prognosis and the activity of new therapies; in particular, there is a strong association between the minimum HIV RNA achieved in the first 16 weeks and subsequent clinical response. CD4 cell counts are independently predictive of response.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:Previous studies on patients treated with potent antiretroviral therapy have shown that viral clearance rates do not tend to change between early and advanced HIV-1 infection. Our objective was to investigate whether the other major aspect of virus dynamics, viral replicative capacity, does change.In vitrowork has indicated that the viral replicative capacity increases butin vivoevidence has been lacking.Methods:As anin vivomeasure of the viral replicative capacity, we studied the rate of rebound of plasma HIV RNA level during a 1-week therapy interruption in previously untreated patients who had received 2 weeks of antiretroviral therapy.Results:Such therapy in five previously drug-naive patients with high CD4 lymphocyte counts (mean, 611×106/l) and five patients with low counts (mean, 49×106/l) led to a mean 2.2log10copies/ml decrease in plasma HIV-1 levels (from 5-6log10copies/ml) in 2 weeks. This was similar in the two groups. Interruption of therapy for the ensuing week resulted in a stable HIV-1 level for approximately 2 days followed by a rebound towards pretherapy level, which was much more marked in the patients with low CD4 cell counts (estimated mean rise 2.22log10versus 1.06log10copies/ml;P<0.02). After restarting therapy, HIV RNA levels returned to pre-interruption levels.Conclusions:These findings need confirmation, but the ability of HIV-1 to replicatein vivoappears to increase during HIV-1 infection. This increased replicative capacity, for which there are several potential explanations, may be the cause of gradual CD4 lymphocyte depletion.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To identify genotypic drug resistance patterns of HIV-1 in patients who were extensively pretreated with anti-HIV drugs and not responding to their current antiretroviral combination therapy.Methods:Drug susceptibility of the viruses was tested by a phenotypic recombinant virus assay. Genotypic analysis of HIV resistance was performed by sequencing of the amino-terminal part of the corresponding reverse transcriptase (RT) gene (amino acids 1-280) for serum-derived and recombinant viruses.Results:Among viruses from 92 patients studied, three (3%) viruses contained a T215Y amino-acid change as well as a previously unseen combination of an amino-acid change at codon 67 (N→E/S) and a two amino-acid insertion between codons 68 and 69 of the RT gene of HIV-1. Phenotypic resistance analysis showed high levels of resistance to zidovudine, lamivudine and stavudine (in all patients) and moderate levels of resistance to didanosine and zalcitabine (in two patients), whereas neither serum-derived nor recombinant viruses contained previously known amino-acid changes conferring resistance to didanosine, zalcitabine, lamivudine and stavudine. However, all recombinant viruses contained an insertion of two amino acids between codons 68 and 69 of RT as well as an amino-acid change at codon 67, as was seen in the serum-derived viruses.Conclusions:Antiretroviral therapy including zidovudine may yield replicating viruses with a two amino-acid insertion in RT in combination with amino-acid changes at codons 67 and 215, which are highly resistant to lamivudine and stavudine on top of zidovudine and have unpredictable susceptibility to didanosine and zalcitabine despite lack of previously reported corresponding resistance-associated amino-acid changes. It is currently unknown what regimens can induce the emergence of this type of multidrug-resistant viruses. This will only be elucidated when resistance assays are capable of detecting these mutants.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To assess the efficacy of combination therapy that includes ritonavir in HIV-1 infected children.Design:A monocentric retrospective study.Patients and Methods:Twenty two children with a minimum follow-up of 6 months under triple therapy including ritonavir were analysed for treatment efficacy. At entry, all the patients were protease inhibitor naive and all but two had received previous antiretroviral therapy during a median period of 5 years. Their initial median CD4+ lymphocyte count and viral load were 121×106/l and 5.08 log10copies/ml, respectively. Clinical and biological evaluation included clinical assessment every 6 weeks and determination of CD4 cell count and HIV-RNA concentration every 3 months.Results:Median length of follow-up on triple therapy was 15 months (range: 7-21 months). Neither progression in the CDC classification nor death occurred. No significant change in mean weight SD scores was noted when baseline values were compared with values obtained after 1 year of triple therapy. Median CD4 count increases were of 210×106/l, 415×106/l, and 472×106/l cells at 6, 12, and 18 months, respectively. Among the patients baseline characteristics, neither age nor initial CD4 cells count influenced the magnitude of immunologic improvement. There were median decreases of 1.14, 0.95, and 1.5 log10per ml of plasma in the concentration of viral RNA at 6, 12, and 18 months respectively. Seven patients maintained an undetectable viral load when under treatment. The introduction of at least one new reverse transcriptase inhibitor at the initiation of triple therapy correlated significantly with a greater viral suppression.Conclusion:Despite variable viral response, antiretroviral-experienced HIV-infected children demonstrated a substantial CD4 cell increase during a median period of 15 months of ritonavir containing combination therapy.

ISSN:0269-9370    

出版商:OVID    

年代:1999

数据来源: OVID