摘要:

A retrospective study was set up to investigate the frequency of zidovudine (ZDV)-resistant HIV-1 in infected newborns after ZDV prophylaxis in the French Perinatal Cohort study.Nucleotide sequence analysis was carried out from 34 infants' isolates and 18 maternal plasma samples. Mutations related to ZDV resistance were found in the HIV-1 reverse transcriptase in 7 of 34 children (20%). Evidence of mother-child transmission of ZDV-resistant HIV-1 was found in 4 cases. Phylogenetic analysis showed that 14 of 34 HIV-1 isolates from the infants belonged to non-B subtypes. The presence of ZDV resistance-encoding mutations in the newborn isolates was associated with a longer total duration of exposure to ZDV. In a context of a wide HIV-1 variability, ZDV resistance can be one of the factors contributing to mother-child transmission.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets, measures of disease activity, and response to highly active antiretroviral therapy (HAART).DesignFourteen untreated HIV-1–infected patients, 18 patients at 3-to 4-weeks after beginning HAART, and 35 uninfected control subjects were studied.MethodsFour-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure their expression of CCR5, CXCR4, and CD38.ResultsHIV-1–infected patients had higher CCR5 levels and lower CXCR4 levels on CD4 and CD8 T cells and their CD45RO/CD45RA subsets than control subjects did. However, CCR5 elevation was statistically significant only for CD4 T cells and their subsets, and CXCR4 depression was significant for CD8 T cells and their subsets (and for CD4:CD45RO cells). The elevation of CCR5 and depression of CXCR4 were not due to shifts in CD45RO/CD45RA subset proportions but to upregulation or downregulation within the subsets. CCR5 elevation on CD4 T cells was significantly restored toward normal by HAART, but the CXCR4 depression was not. CCR5 expression but not CXCR4 expression correlated with other measures of immunodeficiency (CD4 T-cell levels), active infection (viral load), and cellular activation (CD38).ConclusionsCCR5 elevation is a concomitant of immune activation and viral replication that occurs in HIV-1 infection, but the relation of CXCR4 depression to severity of infection, disease progression, and response to therapy remains undefined.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the efficacy and tolerability of a triple nucleoside reverse transcriptase inhibitor combination of zidovudine, lamivudine, and didanosine therapy.DesignA randomized open-label trial.PatientsAntiretroviral-naive HIV-infected patients with CD4+cell counts of 100 to 500 cells/&mgr;l.MethodsA total of 106 patients were randomly assigned to 300 mg of zidovudine (200 mg for body weight <60 kg) twice daily plus 150 mg of lamivudine twice daily plus 200 mg of didanosine (125 mg for body weight <60 kg) twice daily (n= 53) or to zidovudine plus lamivudine (n= 53) for 48 weeks.Main Outcome MeasuresDegree and duration of reduction of HIV-1 RNA load and increase in CD4+cell counts from baseline and development of drug-related toxicities.ResultsAt 48 weeks, triple drug therapy showed greater declines in plasma HIV-RNA levels from the beginning of treatment than double drug therapy (1.86 vs. 1.15 log10copies/ml, respectively;p< .001). The proportions of patients with HIV-RNA <50 copies/ml in an intention-to-treat analysis were 54.7% (29 of 53 patients) and 11.3% (6 of 53 patients) in the triple and double drug therapy, respectively (p= .001). There was no significant difference in increase of CD4 count.ConclusionTriple drug therapy with zidovudine, lamivudine, and didanosine was significantly more effective in inducing sustained immunologic and virologic responses than the double combination of zidovudine and lamivudine.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The purpose of the current study was to determine the efficacy and safety of nevirapine combined with nelfinavir and two nucleoside reverse transcriptase inhibitors (NRTIs) in patients previously exposed to highly active antiretroviral therapy (HAART). In a prospective, open-label, randomized study, 56 HIV-infected adults who had received HAART, including saquinavir hard gel capsule, ritonavir, or indinavir, were randomly assigned to receive nevirapine in addition to nelfinavir and two NRTIs. The proportion of patients who achieved an undetectable viral load (plasma HIV-RNA <200 copies/ml) at weeks 24 and 36 was significantly higher in the nevirapine group than in the control group (55% and 52% vs. 22% and 22%;p= .015 andp= .047). No differences in CD4 cell count or clinical outcome were observed. In the nevirapine group, 17% of patients discontinued treatment because of rashes. We conclude that the addition of nevirapine, when switching from one protease inhibitor–containing regimen to one containing nelfinavir, has a substantial effect on viral suppression.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether initiation of antiretroviral therapy that includes the protease inhibitor indinavir causes insulin resistance or abnormal B-cell function in study subjects with HIV infection.MethodsNonwasted, HIV-infected study subjects who did not have concurrent diabetes were prospectively evaluated by oral and intravenous glucose tolerance testing at baseline, at 2 weeks after starting indinavir monotherapy, and at another 6 weeks after initiating indinavir-based triple-therapy.ResultsMean CD4 count at entry was 282 cells/&mgr;l and median HIV RNA was 33,000 copies/ml; all experienced a virologic response. Fasting glucose increased from 83.2 ± 3.7 mg/dl at baseline to 86.8 ± 3.2 at week 2 and 91.7 ± 3.5 at week 8 (p= .003). Insulin sensitivity by minimal model analysis decreased by 30.5% over 8 weeks, from 3.83 ± 0.63 min−1per &mgr;U/ml × 10−4to 3.09 ± 0.53 at week 2 and 2.66 ± 0.35 at week 8 (p= .01). Insulin secretion by the acute insulin response to intravenous glucose did not change (baseline 822 ± 283 &mgr;U/ml × min, week 8 880 ± 289;p= 0.4), and the insulin response to oral glucose (30 minute insulin:glucose ratio) fell from 1.69 ± 0.54 &mgr;U/ml per mg/dl at baseline to 1.18 ± 0.34 at week 8 (p= .05).ConclusionDuring 8 weeks of indinavir-based therapy, fasting glucose increased and insulin sensitivity decreased, without a compensatory increase in insulin release. This combination of insulin resistance without augmented B-cell response may explain the hyperglycemia and other metabolic abnormalities seen in some protease inhibitor–treated patients.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo examine the feasibility and acceptance of HIV testing among youth in acute substance abuse treatment.MethodsYouth, aged 18 to 25 years old, in state-funded inpatient detoxification completed a confidential demographic/risk behavior questionnaire, and were offered a choice of no testing, serum-based testing, or oral fluid (Orasure, Epitope, Inc., Beaverton, OR, U.S.A.) HIV testing.ResultsIn all, 74% of 204 participants accepted HIV testing. In a multivariate model, female gender (odds ratio [OR], 0.32; 95% confidence interval [CI] 0.14–0.74) and having been recently tested (OR, 0.11; 95% CI, 0.05–0.26) were independently associated with refusing testing. Recent sexual activity (OR, 5.4; 95% CI, 1.5–20.4), recent use of methamphetamines (speed) or a combination of cocaine and heroin (speedball) (OR, 3.8; 95% CI, 1.6–9.0), and a recent perceived risk for HIV (OR, 4.6; 95% CI, 1.9–10.9) were independently associated with test acceptance. Thus, 150 of 150 (100%) chose the Orasure test. Overall, 64.6% (97 of 150) of those tested received their results, but among participants requiring a follow-up appointment to learn test results, only 9.2% (8 of 87) returned.ConclusionsHIV testing is feasible and acceptable in this population. All patients preferred Orasure testing to a serum enzyme-linked immunosorbent assay (ELISA). Most youth tested in detoxification will only learn their results if they are provided during treatment. Rapid HIV testing with same-day results could improve follow-up rates.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivePrevious studies have shown a decrease in hospitalization rates associated with the introduction of highly active antiretroviral therapy (HAART). To evaluate hospitalization rates and patterns in discharge diagnoses that changed between 1995 and 1998 and to examine risk factors for hospitalization in HIV-positive patients, we conducted a cohort study.Patients and MethodsAll inpatient hospitalizations of 2,151 HIV-positive patients enrolled in our university-based HIV clinic between January 1, 1994 and December 31, 1998 with a CD4 count within a 6-month calendar semester were examined to evaluate hospitalization rates, discharge diagnoses, and intensive care department use. Negative binomial regression was used to assess the effect of various risk factors on hospitalization.ResultsHospitalization rates decreased between 1995 and 1996 but increased between 1997 and 1998. In multivariate regression, female gender (incidence rate ratio [IRR], 1.45;p< .001), injection drug use (IRR, 1.36;p< .001), and having received no antiretroviral therapy were strong predictors of total hospitalization. White race, low CD4 count, and no antiretroviral treatment were strong predictors of hospitalization for an opportunistic infection. Female gender (IRR, 1.45;p< .001), African-American ethnicity (IRR, 1.22,p= .05), no antiretroviral treatment, and low CD4 counts were predictive of higher hospitalization rates for nonopportunistic infection–related diagnoses. Intensive care department–use was associated with white ethnicity (IRR, 1.86;p= .028), heterosexual transmission of HIV (IRR, 1.90;p= .009), no antiretroviral treatment, and low CD4 count at enrollment.ConclusionsOur data indicate that hospitalization rates decreased between 1995 and 1997 after introduction of HAART, but that they then increased between 1997 and 1998, particularly for diagnosed nonopportunistic infections. If these trends continue, it indicates that patients may be developing previously unseen comorbidities and that HAART may have reached or exceeded a threshold in its effectiveness in reducing the clinical morbidity that results in hospital admission.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

SummaryThe effect of ritonavir 400 mg/saquinavir 400 mg twice daily on the stereoselective pharmacokinetics of methadone was examined in 12 HIV-infected, methadone-using study subjects.DesignA 24-hour methadone pharmacokinetic study was performed before antiretroviral therapy was begun and after 15 days of therapy. Methadone concentration was measured by a chiral plasma assay because the drug is administered as a racemic mixture of R- and S-methadone, but only the R-isomer is active. Both changes in plasma protein binding and changes in objective and subjective opioid effect were monitored.ResultsRitonavir/saquinavir administration was associated with 40% decrease in total S-methadone AUC0–24hrand 32% decrease in R-methadone area under the curve (AUC)0–24hr, and both changes were statistically significant (p= .001 for both). When AUC was corrected for the changes in protein binding induced by ritonavir/saquinavir, R-methadone free AUC0–24hrdecreased 19.6% whereas the S-methadone decreased 24.6%, neither of these changes was statistically significant (p= .129 andp= .0537, respectively). This change in methadone exposure was not associated with any evidence of withdrawal from narcotics and no modification of methadone dose was required.ConclusionsOur data indicate that ritonavir/saquinavir administration is associated with induction of metabolism of methadone but this is greater for the inactive S-methadone. However, approximately 37% of the decrease in the total R-methadone exposure can be explained by protein binding displacement. Ritonavir/saquinavir can be used in HIV-infected people taking methadone without routine dose adjustments.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID