摘要:

ObjectiveTo compare drug-resistant variants from untreated (naive) and treated patients infected with clade B or C virus.MethodsConsecutive samples (165) from patients throughout Israel were analyzed. All those in the treated group were failing highly active antiretroviral therapy.ResultsThere were 78 clade C (20 naive) and 87 clade B (14 naive) with significant differences in the prevalence of known drug-resistance mutations between the clades: in naive patients in the protease region M36I 7% and 95% (P< 0.0001), K20R 0% and 27% (P= 0.063), A71V 18% and 0% (P= 0.063), M46I 0% and 13%, and V77I 18% and 0% (P= 0.063), respectively, and in the reverse transcriptase region A98G/S 0% and 20% (P= 0.12), respectively. Most clade C viruses also showed significant differences from clade B consensus sequence at additional protease sites: R41K 100%, H69K/Q 85%, L89M 95% and I93L 80% (P< 0.0001). There were also significant differences (P< 0.03 to < 0.0001) in treated patients in clades B and C: in the protease region L10I 40% and 12%, M36I 26% and 95%, L63P 67% and 40%, A71I 38% and 7%, G73I and V77I 18% and 0%, I84V 16% and 3%, and L90M 40% and 12%, respectively; in the reverse transcriptase M41L 41% and 17%, D67N 41% and12%, K70R 30% and 7%, T215Y 48% and 29%, K219Q 21% and 7%, and A98G/S 3% and 24%, respectively.ConclusionSignificantly differences between clade B and C viruses may be associated with development of differing resistance patterns during therapy and may affect drug utility in patients infected with clade C.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundIn Mbeya, a rural region of southwest Tanzania, HIV-1 subtypes A, C and D have been co-circulating since the early 1990s.ObjectiveTo define to what extent the co-existence of subtypes has led to recombinant HIV-1 strains and whether there is evidence for epidemic spread of any circulating recombinant form.MethodsNine HIV-1-seropositive young adults from Mbeya Town with no evident high-risk behaviour contributed peripheral blood mononuclear cells for this study. Nine virtually full-length-genome-sequences were amplified from this DNA and phylogenetically analysed.ResultsOut of the nine samples, two were subtype A (22%), two were subtype C (22%) and five were recombinants (56%): four A/C recombinants and one C/D recombinant. None of the recombinants were related to each other; all of them had different mosaic structures. Most of the genome in the recombinants was subtype C.ConclusionA high proportion of unrelated intersubtype recombinants, none of them apparently spreading in the population, may be present in southwest Tanzania.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Objective(s)To compare antiretroviral resistance susceptibility testing of patient HIV-1 strains using genotype and phenotype methods.DesignEighteen plasma samples with viral load > 2000 HIV-1 RNA copies/ml were randomly selected for testing by both methods. Disease and treatment data were available for all patients.MethodsSamples were analysed genotypically using a kit assay (HIV-1 Genotyping Systems, Applied Biosystems), performed by the Clinical Research Laboratory at Macfarlane Burnet Centre for Medical Research. Samples were analysed phenotypically using a rapid phenotypic assay (PhenoSenseTMHIV, ViroLogic), performed by the manufacturer. Results from both methods were interpreted using a defined protocol. Each susceptibility assay was performed and interpreted by individuals unaware of either the clinical data or the results of the other susceptibility assay. Concordance was defined categorically as either the presence of reduced susceptibility (> 2.5-fold change) in the phenotypic assay and resistance associated mutations in the genotypic assay, or the absence of these findings in both assays.ResultsConcordance between phenotypic and genotypic susceptibility testing was 81% for nucleoside reverse transcriptase inhibitors, 91% for non-nucleoside reverse transcriptase inhibitors and 90% for protease inhibitors. Complete concordance between phenotype and genotype for all 14 drugs evaluated was observed in three (17%) patient samples.ConclusionsPhenotypic and genotypic susceptibility appear to provide similar results. However, interpretation of genotypic results can be complicated, and both methods still require clinical validation.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo assess virological response in lymphoid tissue and its impact on the durability of response in plasma in HIV-1-infected persons who achieved sustained suppression of plasma viraemia with different antiretroviral regimens.MethodsConsecutive patients on first-line antiretroviral therapy were included if they had a plasma HIV-1 RNA viraemia < 20 copies/ml within the last 6 months and tonsillar tissue accesible for biopsy. First-line therapy contained two nucleoside analogues: alone (2NRTI group, n = 3); plus a HIV-1 protease inhibitor (PI group, n = 11) or plus nevirapine (NVP group; n = 16). Patients were followed until virus was detectable in plasma, they changed therapy or were lost to follow-up.ResultsTonsillar HIV-1 RNA could be detected (> 100 copies/mg) in 10 patients: one in the PI group (9%), six (38%) in the NVP group and in all three patients in the 2NRTI group. Primary resistance mutations could be detected in only 2 of these 10 patients. After a median of 9 months after the biopsies, viral suppression in plasma had failed in 6 of these 10 patients whereas failure had only occurred in 1 out of 20 with initially undetectable viral load in lymphoid tissue (P= 0.01; log rank test).ConclusionsIn patients with sustained viral suppression in plasma, triple therapy including a HIV-1 protease inhibitor was more potent than triple therapy containing nevirapine or dual therapy with nucleoside analogues to reduce viral burden in lymphoid tissue. A worse response in lymphoid tissue could not be explained by local selection of resistance and was associated with a less durable virological response in plasma.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo evaluate the impact of response to highly active antiretroviral therapy (HAART) on the natural history of AIDS non-Hodgkin's lymphoma (NHL) and to analyse the feasibility, efficacy and toxicity of HAART in combination with chemotherapy.DesignProspective observational study in two AIDS clinical centres in Italy.MethodsAll consecutive HIV-infected patients with NHL were included (n = 44; 48% high-risk group) and prospectively followed for 27 months. HAART was administered concomitantly with chemotherapy. The association between response to HAART and clinical presentation, response to chemotherapy and toxicity was analysed by univariate and multivariate models. Survival analysis was performed by Kaplan–Meier estimates and the Cox proportional hazards regression model.ResultsA complete response (CR) to chemotherapy was achieved in 71% of HAART responders and 30% of non-responders. Virological response to HAART was the only variable associated with tumour response on multivariate analysis. A higher relative dose intensity (RDI) of chemotherapy was administered in patients with virological response compared with those without. The probability of 1 year survival was higher in patients with virological or immunological response. At Cox regression analysis, immunological response, a higher RDI and a CR to chemotherapy were all associated with a reduced risk of death.ConclusionIn HIV-infected patients with NHL, response to HAART was strongly associated with a better response to chemotherapy and prolonged survival. Concurrent treatments were well tolerated, and HAART-responder patients could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas, combining HAART with chemotherapy could be a feasible and effective approach.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the therapeutic response and investigate the significance of polymorphic codons in African patients receiving highly-active antiretroviral therapy (HAART).Design and methodsAfrican patients were identified from the St Mary's Hospital HIV-1 database. Clinical outcome was assessed by viral load and CD4 cell count. Pre- and post-therapy sequences ofRTandproteasewere analysed. The impact of subtype and individual polymorphic codons on therapeutic outcome was assessed statistically (Fishers exact and χ2tests) and phylogenetically (Jukes and Cantor).ResultsOf 79 drug-naive African patients who were prescribed HAART, 60 remained undetectable for 1 year, with no differences detected in the clinical response to non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-containing regimes. Country of origin, sex and viral subtype had no impact on outcome of HAART. A total of 133 polymorphisms were identified inpol(37 inproteaseand 96 inRT), with a mean of 9.0 inproteaseand 22.3 inRTper patient. There was no significant difference in the overall numbers of polymorphisms per patient, and no single polymorphism had any impact on clinical outcome. Sequences from ‘failing’ patients experiencing viral rebound produced few mutations known to be associated with drug resistance, suggesting minimal drug pressure.ConclusionsThe response of patients infected with African subtypes of HIV-1 to HAART appears to be independent of regime, HIV-1 clade and baseline polymorphisms. Non-B subtypes are fully sensitive to HAART and, accordingly, therapy should not be withheld from African patients for reasons of viral diversity.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundTherapy with a HIV protease inhibitor is associated with elevations in cholesterol and triglycerides. HMG-CoA reductase inhibitors (`statins') are the established therapy for persons with primary hypercholesterolaemia. Because of drug interactions, pravastatin may represent the preferred choice in those taking HIV protease inhibitors.DesignA randomized, open-label comparative 24 week trial of dietary advice alone or with pravastatin in 31 male patients established on protease inhibitor-based regimens for greater than 12 weeks with viral load < 500 copies/ml and cholesterol > 6.5 mmol/l.ResultsThere were no significant clinical or laboratory events and no patient discontinuation secondary to adverse effects. Viral rebound did not occur. Relative to baseline, total cholesterol at week 24 fell significantly in the pravastatin (1.2 mmol/l; 17.3%) (P< 0.05) but not in the dietary advice (0.3 mmol/l; 4%) group. The difference between the two groups approached significance at week 24 (P= 0.051). This fall was accounted for entirely by a reduction in low density lipoprotein [calculated change 1.24 mmol/l (19%) and 0.07 mmol (5.5%) in pravastatin and dietary advice groups, respectively] as high density lipoprotein rose non-significantly by 0.6 mmol/l in both groups. Weight, basal metabolic rate, fasting glucose and triglycerides did not change significantly in either group.ConclusionsDietary advice plus pravastatin significantly reduced total cholesterol in HIV-positive individuals taking protease inhibitors, without significant adverse effects. The inclusion of pravastatin substantially increases the magnitude of the change, which is comparable with changes achieved in endogenous hyperlipidaemia.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the incidence ofPneumocystis cariniipneumonia (PCP) after discontinuation of either primary or secondary prophylaxis.DesignThis was a prospective, non-randomized, non-blinded study.SettingTwenty-five University-based AIDS Clinical Trials Group units.ParticipantsParticipants either had a CD4 cell count ⩽ 100 × 106/l at any time in the past and no history of confirmed PCP (group I; n = 144), or had a confirmed episode of PCP ⩾ 6 months prior to study entry (group II; n = 129). All subjects had sustained CD4 cell counts > 200 × 106/l in response to antiretroviral therapy.InterventionsSubjects discontinued PCP prophylaxis within 3 months or at the time of study entry. Evaluations for symptoms of PCP and CD4 cell counts were performed every 8 weeks. Prophylaxis was resumed if two consecutive CD4 cell counts were < 200 × 106/l.Main outcome measure(s)The main outcome was development of PCP.ResultsNo cases of PCP occurred in 144 subjects (median follow-up, 82 weeks) in group I or in the 129 subjects (median follow-up, 63 weeks) in group II (95% upper confidence limits on the rates of 1.3 per 100 person-years and 1.96 per 100 person-years for groups I and II, respectively). Eight subjects (five in group I and three in group II) resumed PCP prophylaxis after two consecutive CD4 cell counts < 200 × 106/l.ConclusionsThe risk of developing initial or recurrent PCP after discontinuing prophylaxis is low in HIV-infected individuals who have sustained CD4 cell count increases in response to antiretroviral therapy. Neither lifelong primary nor secondary PCP prophylaxis is necessary.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the antiviral efficacy, safety and adherence in patients switched to an abacavir-containing nucleoside reverse transcriptase inhibitor (NRTI) regimen after long-term HIV-1 RNA suppression with a dual NRTI/protease inhibitor (PI) combination.MethodsIn an open-label, multicentre study, patients receiving 2NRTI plus PI for at least 6 months, with a history of undetectable plasma HIV-1 RNA since the initiation of therapy and plasma HIV-1 RNA < 50 copies/ml at screening, were randomly assigned to replace the PI with abacavir (n = 105) or continue the same treatment (n = 106). Clinical assessments included plasma HIV-1 RNA, chemistry, haematology, lymphocyte counts, and adverse event reports. Adherence to treatment was assessed by patient self-report.ResultsA significantly longer time to treatment failure was demonstrated in the abacavir arm compared with the PI arm (P= 0.03) while treatment failure was experienced by significantly more patients in the PI arm: 24 (23%) versus 12 (12%) (P= 0.03). Therapy-limiting toxicity led to treatment failure in eight versus 14 cases in the abacavir and PI arms, respectively, whereas virological rebound was the cause in four versus two cases. Significant reductions in cholesterol and non-fasting triglyceride plasma levels at 48 weeks were observed in the abacavir arm (P< 0.001 andP= 0.035, respectively). The number of patients reporting no difficulty in taking their therapy showed a marked increase from baseline in the abacavir arm.ConclusionThe replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression, significant improvements in lipid abnormalities and enhanced ease of dosing.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo define age at entry into Tanner stages in children with perinatal HIV-1 infection.DesignMulticentre longitudinal study including 212 perinatally HIV-1-infected children (107 girls and 105 boys) followed-up during puberty (from 8 and 9 years onwards in girls and boys, respectively). Healthy children (843 girls and 821 boys) provided reference percentiles. P2 or B2 stages in girls and P2 or G2 stages in boys defined onset of puberty.MethodsThe cumulative probability [95% confidence limit (CI)] of entry into each stage at different ages was estimated by the Kaplan–Meier product-limit method; differences were evaluated by log rank test. Relationships were tested using the Spearman's rank correlation coefficient.ResultsAges of girls [years (95%CI)] at P2 [12.9 (12.6–13.2)], P3 [13.4 (13.0–13.8)], P4 [14.6 (14.0–15.2)], B2 [12.7 (12.2–13.2)], B3 [13.3 (12.8–14.0)] and B4 [14.6 (14.0–15.2)] stages were > 97th percentile (⩾ 21 month delay) of controls. Ages of boys [years (95%CI)] at P2 [12.6 (12.1–13.1)], P3 [13.9 (13.4–14.4)], P4 [14.9 (14.2–15.6)], G2 [12.1 (11.5–12.7)], G3 [13.6 (13.1–14.1)] and G4 [14.9 (14.1–15.7)] stages were at the 75–97th percentiles (⩽ 15 month delay). Age at onset of puberty was not related to clinical and immunological condition, antiretroviral treatment, weigh for height and age at onset of severe disease or immune suppression.ConclusionPerinatal HIV-1 infection interferes with sexual maturation. The mechanisms by which this occurs should be elucidated and intervention strategies designed. Intervention could save much psychological distress, since associated linear growthfailure can exacerbate adolescents’ feelings of being different and unwell.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID