摘要:

ObjectivesTo assess the effectiveness of two triple antiretroviral combinations (2 nucleoside reverse transcriptase inhibitors [NRTIs] + 1 protease inhibitors [PI] vs. 2 NRTIs + 1 nonnucleoside reverse transcriptase inhibitor [NNRTI]) to correct T-cell subsets abnormalities and to restore immune functions in asymptomatic antiretroviral-naive HIV-1–infected patients with a baseline CD4 T-cell counts >500/mm3and plasma viral load >5000 copies/mL.Design and MethodsTwenty randomized patients from 2 cohort studies receiving either stavudine (d4T) + lamivudine (3TC) + indinavir (n= 9), or d4T + didanosine (ddI) + nevirapine (NVP) (n= 11) were studied. Viral load, T-cell subsets and T-cell functions were analyzed at baseline and after 1 year of treatment.ResultsAfter 1 year of follow-up, the PI regimen was significantly more effective in reducing plasma and lymphoid tissue VL to undetectable levels. A significant increase in CD4+T cells was observed in patients treated with PI (p= .0007) compared with those treated with NVP. Percentages of CD8+T-cells and of activated CD8+T-cells (CD38+and DR+as well as memory CD45RO+) decreased in all patients. An increase of the CD28+subset of CD8+T-cells also occurred in both groups of treatment. Naive T cells were maintained in the CD4+subset and augmented in the CD8+subset in all patients. In both PI and NVP groups, memory CD4+T-cells increased significantly (p= .03). Peripheral blood mononuclear cell responsiveness to polyclonal stimuli and to tetanus toxoid and cytomegalovirus (CMV) antigen was similar in both groups of treatment. HIV-infected patients treated for 1 year with both triple combinations lacked significant T-cell responsiveness to HIV-1 proteins.ConclusionsThese data suggest that immune reconstitution achieved after 1 year of therapy with PI-containing or PI-sparing regimens is similar, despite the higher effectiveness of PI-containing regimens in reducing viral load. Additional therapeutic approaches should be designed to restore HIV-1–specific responses.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The role of maternal humoral immune response and viral load was analyzed in relation to the incidence of mother-to-child transmission (MTCT) of infants born to HIV-1 subtype C infected mothers. High levels of viral RNA in the serum correlated with MTCT as did high titers of subtype C consensus V3 peptide binding antibodies (BA) and neutralizing antibody (NA) to subtype B HIV-1MN. Logistic regression analysis showed that maternal viral load and V3 peptide subtype C BA were independent predictors for MTCT, odds ratio (OR) = 2.22 and OR = 2.52, respectively. No correlation between NA to homologous HIV-1 subtype C virus and MTCT was found. BA to V3 peptides may provide a rapid inexpensive method that can be used to determine the risk of HIV-1 MTCT.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Decreased insulin sensitivity, hyperlipidemia, and body fat changes are considered as risk factors for coronary heart disease (CHD). A clustering of such factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired fibrinolysis and increased coagulation are additional independent risk factors for CHD. We studied the effects of protease inhibitor (PI)–containing highly active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in 363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and 97 were treatment naive. The fasting plasma levels of insulin, glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and fibrinogen were evaluated together with the areas of visceral adipose tissue and the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol; visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were significantly increased in patients receiving PI-containing HAART compared with treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly higher in patients receiving PI-containing HAART. PAI-1 levels were higher in individuals with MSDR but also in patients without MSDR who were receiving PI-containing HAART. PAI-1 was independently correlated to use of PI-containing HAART, triglyceride level, insulin level, and body mass index (p< .001). These findings suggest that patients receiving PI-containing HAART have decreased fibrinolysis and increased coagulability, which may thus represent additional risk factors for cardiovascular disease in this patient group.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Total body bone mineral content (TBBMC) was measured by dual energy x-ray absorptiometry in a cross-sectional study of 51 prepubertal HIV-infected children and 262 healthy prepubertal children aged 4.2 to 14.7 years. The mean TBBMC ± SD was lower in HIV-positive children than in HIV-negative controls (955 ± 325 vs. 1,106 ± 273 g, respectively;p= .0006). Reductions in TBBMC remained in the HIV-positive group after adjusting for age, sex, and race by analysis of covariance (p< .001). Differences in TBBMC between HIV-positive and HIV-negative groups persisted when height and weight were also accounted for in the analysis (p= .027). The magnitude of the difference in TBBMC between the groups increased with age. In the HIV-positive group, no associations were observed between TBBMC and use of a protease inhibitor, duration of treatment with antiretroviral medications, viral load, or CD4 cell count. TBBMC is decreased in HIV-infected children. As a result of compromised bone mineral accrual, HIV-infected children may be at increased risk for osteoporosis and related complications.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The pharmacokinetics of nelfinavir (NFV) in neonates younger than 4 weeks of age was assessed. Three cohorts of HIV-exposed neonates were enrolled in cohorts to receive 15, 30, and 45 mg of NFV/kg twice daily in combination with stavudine and didanosine for 4 weeks after birth. Trough NFV concentrations (Cmin) were measured at 1 and 7 days of age. Intensive pharmacokinetic evaluations were performed at 14 and 28 days of age. The median NFVCminvalues in the 15 mg/kg (6 patients), 30 mg/kg (5), and 45 mg/kg (11) cohorts at 1, 7, 14, and 28 days of age were 0.19, 1.21, 0.51, and 0.33; 1.02, 3.18, 0.73, and 0.55; and 0.67, 3.21, 0.70, and 0.73 mg/L, respectively. The median area under the plasma concentration–versus–time curve values over 12 hours in the three cohorts at 14 and 28 days of age were 14.4 and 8.7, 19.4 and 15.8, and 23.4 and 18.5 (h · mg)/L, respectively. No serious adverse events were observed. In conclusion, the systemic exposure of NFV decreased after 7 days of age, possibly because of hepatic enzyme maturation, autoinduction of NFV metabolism, and/or changes in NFV absorption. The highly variable systemic exposure observed in the study indicates that therapeutic drug monitoring seems warranted to ensure adequate NFV dosing in this population.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo determine the feasibility of switching therapy for HIV-1–infected patients with plasma viral loads of <50 HIV-1 RNA copies/mL who are receiving twice-daily saquinavir soft-gelatin capsules (SQV-SGC) plus dual nucleoside reverse transcriptase inhibitors (NRTIs) to a regimen containing once-daily SQV-SGC/ritonavir (RTV).DesignTherapy for patients with plasma viral loads of <50 copies/mL after 2 years of treatment with twice-daily SQV-SGC (1400 mg) plus zidovudine/lamivudine or didanosine/stavudine was switched to once-daily SQV-SGC/RTV (1600/100 mg) with continuing NRTI treatment.MethodsSafety and efficacy (determined by plasma viral load and CD4 cell count) were evaluated (week 24). For 12 patients, steady-state plasma pharmacokinetics of SQV was determined (week 4).ResultsOnce-daily SQV-SGC/RTV was well tolerated. No patient changed regimens. After 24 weeks, 64 (93%) of 69 patients had plasma viral loads of <50 copies/mL (the remaining 5 patients had plasma viral loads of <300 copies/mL). The median CD4 cell count increased from 534/mL at the start of once-daily SQV-SGCs/RTV to 695/mL after 24 weeks (p< .001). Compared with the preceding 24 weeks of treatment with twice-daily SQV-SGC, the CD4 cell count improved significantly during once-daily SQV-SGC/RTV therapy (p< .001). All patients maintained SQV trough concentrations (C24h) of >0.05 mg/L. Median values for the area under the plasma concentration–versus–time curve from 0 to 24 hours (AUC0–24h), maximal concentration (Cmax), andC24hfor SQV were 48.1 (h·mg)/L, 6.98 mg/L, and 0.17 mg/L, respectively. Body weight was inversely correlated with SQV AUC24handC24h(p< .01).ConclusionsClinical and pharmacokinetic data support once-daily SQV-SGC/RTV (1600/100 mg) with two NRTIs as a convenient and safe therapeutic regimen to maintain viral suppression and immune function in HIV-1–infected patients with plasma viral loads of <50 copies/mL.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo determine the effects of nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK) of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive, and to assess the effects of EE/NET on the steady-state PK of NVP.MethodsTen HIV-1–infected women underwent intensive PK sampling after single-dose administration of EE/NET (days 0–1). Oral NVP 200 mg once daily (days 2–15), followed by 200 mg twice daily (days 16–29), was added to background potent antiretroviral therapy. On day 30, intensive PK sampling was performed after concurrent administration of NVP 200 mg and a single dose of EE/NET.ResultsConcomitant administration of NVP at steady state with EE/NET resulted in a significant (29%) median reduction in the area under the plasma concentration time curve (AUC∞) and a significant reduction in mean residence time (MRT) and half-life (t½) of EE. There was a significant (18%) median reduction in the AUC∞ for NET that was not associated with a detectable change in NET Cmax, MRT, or t½.ConclusionOral contraceptives should not be the primary method of birth control in women of child-bearing potential who are treated with NVP.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Although the numbers of newly reported diagnoses of AIDS decreased in the 1990s, it is not clear whether they reflect a decreasing number of new HIV infections. Direct measurement of HIV incidence through follow-up cohort studies is difficult and costly. We estimated HIV incidence and trends in incidence among men who have sex with men (MSM) and heterosexual men and women at clinics for sexually transmitted diseases (STDs) by using a recently developed serologic testing algorithm that requires only a single blood specimen. Cross-sectional anonymous serosurveys were conducted at 13 STD clinics in nine cities in the United States from 1991 through 1997. Before anonymous HIV testing, demographic and clinical information was abstracted. Of 129,774 specimens tested, 362 (0.28%) were from persons estimated to be recently infected. Incidence among MSM was 7.1% (95% confidence interval (CI): 4.8–10.3), 14 times higher than that among heterosexuals, which was 0.5% (CI: 0.4– 0.7). Incidence among MSM and heterosexuals remained unchanged during the time studied. Decreasing rates of new AIDS diagnoses in the 1990s do not reflect stable rates of new HIV infections among MSM and heterosexual patients attending these clinics.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ContextThe Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1–infected pregnant women and their infants since 1989.ObjectiveTo evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level.DesignProspective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1–infected women with singleton live births between January 1990 and June 2000.Main Outcome MeasureHIV-1 status of the infant.ResultsHIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%–23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%–12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%–6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0–2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p= .0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7–3.5) for every log10increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09–1.02) and 0.27 (95% CI, 0.08–0.94), respectively.ConclusionLevels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveThe purpose of this study was to describe the variability in highly active antiretroviral therapy (HAART) regimens over time, the extent to which individuals switch, and the characteristics of those who are switching.MethodsWe evaluated data collected between 1994 and 2000 from 1056 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS) who reported initiating HAART. We described the variability and prevalence of changes in HAART regimens between semiannual visits, estimated time to switch using Kaplan-Meier methods, investigated factors associated with a first switch using Cox proportional hazards models, and compared disease markers among women switching or remaining on unchanged HAART regimens.ResultsWe demonstrated a 13-fold increase in the number of unique HAART regimens reported since mid-1996 and showed that the amount of time spent on the first, second, or third regimen is similar, with an 8-month median time to switching or discontinuing the initial HAART regimen. Women who switched had a lower mean CD4 cell count and were more likely to have HIV RNA levels greater than 400 copies/mL. Overall, the percentage of women switching decreased over the course of follow-up (to 37% in September 2000), although the percentage discontinuing therapy altogether increased 2-fold.ConclusionOur findings on the relatively high rate of HAART switching emphasize the complexity of managing and evaluating these therapies.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID