摘要:

Tuberculosis (TB) enhances HIV-1 replication and the progression to AIDS in dually infected patients. We employed pleural TB as a model to understand the interaction of the host with HIV-1 during active TB, at sites ofMycobacterium tuberculosis(MTB) infection. HIV-1 replication was enhanced both in the cellular (pleural compared with blood mononuclear cells) and acellular (pleural fluid compared with plasma) compartments of the pleural space. Several potential mechanisms for expansion of HIV-1 in situ were found, including augmentation in expression of tumor necrosis factor (TNF)-&agr; and the HIV-1 noninhibitory &bgr;-chemokine (MCP-1), low presence of HIV-1 inhibitory &bgr;-chemokines (MIP-1&agr;, MIP-1&bgr;, and RANTES [regulated on activation, normal T expressed and secreted]), and upregulation in expression of the HIV-1 coreceptor, CCR5, by pleural fluid mononuclear cells. Thus, at sites of MTB infection, conditions are propitious both for transcriptional activation of HIV-1 in latently infected mononuclear cells, and facilitation of viral infection of newly recruited cells. These mechanisms may contribute to enhanced viral burden and dissemination during TB infection.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine the probable site of the nephron and the plasma indinavir (IDV) concentration at which intrarenal IDV crystallization occurs.DesignWe performed in vitro crystallization experiments in IDV solutions simulating conditions found in the nephron.MethodsTo determine intrarenal IDV concentrations at which conditions in the nephron allow crystallization, several concentrations of IDV basic solutions (0–800 mM) were titrated from pH 4.0 to higher pH values until crystals formed within 1 minute. Based on the combination of pH and ionic strength at which crystals formed, we determined the site of the nephron at which this combination was first attained. Based on the capacity for concentration at that site, we were able to measure the corresponding plasma IDV concentration.ResultsUnder conditions normally found at the proximal tubule (i.e., pH 6.7 and ionic strength of 200 mM), IDV crystallized at 200 mg/L. Under conditions applying to the loop of Henle, pH 7.4 and ionic strength of 200 mM, IDV crystallized at 125 mg/L, which would correspond to a plasma IDV concentration of 8 mg/L.ConclusionsIDV crystallization is most likely in the loop of Henle and may already start at plasma IDV concentrations as low as 8 mg/L. Increasing hydration does not reduce the risk of IDV crystallization in the loop of Henle but instead prevents IDV crystallization and aggregation in the lower urinary tract. It remains to be confirmed whether prevention of high IDV plasma concentrations will reduce the risk of IDV crystallization in the loop of Henle.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesRash is the most frequent adverse event associated with nevirapine. The use of prednisone has been controversial in this setting. A double-blind placebo-controlled study was performed to evaluate its efficacy in nevirapine-induced rash prevention.DesignMulticentered, randomized, double-blind, placebo-controlled clinical trial with prednisone (30 mg/day × 2 weeks). Inclusion criteria: HIV-1 infection; CD4 count >200 cells/mm3; plasma viral load (PVL) <5 log10copies/ml; nevirapine (200 mg/day × 2 weeks, followed by 200 mg twice daily) plus stavudine and didanosine. Clinical follow-up was performed at 15, 30, and 60 days and thereafter every 2 months.ResultsIn all, 75 evaluable patients were enrolled (39 prednisone/36 placebo). Median baseline CD4+cell count was 390 cells/mm3and PVL, 20,200 copies/ml. Overall, nine cases of rash (12.5%) were detected, seven (18%) in the prednisone group and two (5.5%) in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 0.65–29.3;p= .11). Incidence of moderate-to-severe rashes leading to nevirapine withdrawal was 13.5% (5 of 37) in the prednisone group and 3% (1 of 35) in the placebo group (p= .2). Median time to rash in both groups was 16 days. Adverse events that motivated withdrawal of therapy appeared in 6 patients from the prednisone group (15.4%) and 3 from the placebo group (8.3%) (p= .3).ConclusionShort-term prednisone administration does not prevent nevirapine rash, but might even increase its incidence.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo describe changes in HIV-associated neurocognitive impairment in patients treated with highly active antiretroviral therapy (HAART) for at least 3 years.MethodsProspective, observational study of comprehensive neuropsychologic (NP) testing, neurologic examination, and laboratory measures before HAART and after 6, 15 and 45 months of HAART, on 28 consecutive patients seen in our department since April 1996.ResultsAt baseline, 16 patients were neurocognitively impaired and 12 were not. Among the 16 impaired patients, 5 patients failed to meet the criteria for impairment after 6 months and 9 patients after both 15 and 45 months of HAART, respectively. Statistically significant improvements (p≤ .01) were seen in two of six measures exploring the concentration and speed of mental processing, two of three measures exploring mental flexibility, in one of five measures exploring memory, and in two of two measures exploring fine motor functions. Unimpaired study subjects performed better than impaired ones in 10 of 17 measures at baseline, in eight of 17 after 6 months, in six of 17 after 15 months, and in seven of 17 after 45 months of HAART.ConclusionsDuring the course of HAART, patients experienced a positive and sustained improvement in their neurocognitive performance. However, the presence of 7 of 16 (43.7%) patients with neurocognitive impairment, and the persistence of statistically significant differences in the neurocognitive performance between impaired and unimpaired patients after more than 3 years of HAART, suggests that ongoing HIV-related neurologic damage can occur even during potent antiretroviral treatment.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundHIV-infected injection drug users consistently report poor antiretroviral therapy use and little contact with health care providers. It has been suggested that the clinical setting where patients are seen affects the use of highly active antiretroviral therapy.ObjectivesThe purpose of this study was to determine whether ease of access to medical care affects self-report of taking antiretroviral therapy, particularly among female injection drug users.DesignThe study is a cross-sectional analysis from a prospective cohort study of HIV-infected women.SettingWomen were enrolled at four sites in the United States: Detroit, Michigan, and Providence, Rhode Island, where on-site HIV care and treatment were offered, and Baltimore, Maryland, and the Bronx, New York, where all participants were referred elsewhere for HIV care and treatment.PatientsPatients were HIV-infected women with no AIDS diagnosis or women who were at risk for HIV infection either through self-reported injection drug use since 1985 or through sexual contact.MeasurementsThe study measured self-reported use of antiretroviral therapy (ART) alone or combined withPneumocystis carinii(PCP) prophylaxis in the previous 6 months.ResultsIn multivariate analysis including type of study site (on-site compared with referral care) and injection drug use, any self-reported ART use associated with low CD4 cell count category, older age, and race. However, at on-site care centers, women were equally likely to report ART use regardless of current, former, or no injection drug use, whereas at referral sites only women identified as sexual contacts were more likely to report any ART use, independent of all other variables.ConclusionsEasy access to medical care has an important impact on HIV-infected women receiving ART, particularly those who are active injection drug users.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

MethodsGroups of HIV-infected and HIV-uninfected infants younger than 18 months (mainly younger than 6 months) were compared to identify clinical features that could differentiate the two groups. The HIV-infected group also was compared with HIV-infected children older than 18 months. Recruitment was as follows for the group younger than 18 months: 708 children admitted with sepsis and clinical features suggestive of HIV infection were screened for HIV1 and HIV2 by HIV enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) was undertaken on all ELISA-seropositive blood samples (270). HIV infection was confirmed in 136 (19.2%), 438 (61.9%) were HIV-seronegative, 27 (3.8%) were HIV seroreverters, 36 (5.1%) were HIV-seropositive but PCR negative (uninfected), and 71 (10.0%) were indeterminate. One hundred thirty-six HIV-infected children were compared with 501 uninfected children. Confirmed HIV-infected children older than 18 months attending the pediatric HIV clinic were compared with the 136 HIV-infected children younger than 18 months.ResultsUnder 18 months, the median age of HIV-infected children (n= 136) was 4.0 months (range, 3d–18mo) and the median age of the uninfected children (n= 501) was 1.0 month (range, 3d–18mo). HIV-infected children were more likely to have had injections, chloroquine, and nystatin, and to have attended a health center or hospital (p< .001). In the HIV-infected group, theZscore for weight-for-age was −1.75, length-for-age −0.78, and weight-for-length 1.86, significantly lower scores than those of the uninfected group, which were −0.60, −0.23, and 3.05, respectively (p< .05). The mean head circumference was below the third percentile in 40% of HIV-infected compared with 22% of uninfected children (p< .001). Overall, 56 (8%) children had marasmus, 6 (0.8%) kwashiorkor, and 3 (0.4%) marasmic kwashiorkor. Sixteen percent of the HIV-infected and 7% of uninfected children had marasmus (p< .05). The 1989 revised World Health Organization clinical criteria for diagnosis of AIDS had sensitivity, specificity, and positive predictive values of 28%, 98%, and 93%, respectively. Older than 18 months (n= 109), the median age was 24 months (range, 18–60mo). The following were significantly more common in HIV-infected children older than 18 months than in those younger than 18 months: bacille Calmette-Guérin vaccination scar, parotid enlargement, nonspecific generalized dermatitis, and chronic diarrhea (p< .001). Oral candidiasis was more common in the group younger than 18 months (p< .001). In infants examined in the hospital for infective conditions, oropharyngeal candidiasis, ear discharge, dermatologic disorders, generalized lymphadenopathy, lobar consolidation, hepatosplenomegaly, and failure to thrive, especially marasmus, were important indicators of HIV infection.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Adjudication of clinical events is often used as a quality assurance method in clinical research. During the design of the Viral Activation Transfusion Study (a clinical trial in patients with advanced HIV disease), a set of study endpoints was defined (primarily AIDS-defining conditions), criteria for confirmation of each event type were developed, and an adjudication procedure was established. The adjudication process included 1) an initial review of documentation of each event by two independent reviewers, 2) the opportunity to request additional information, 3) a second review either of additional documentation or of cases in which there was disagreement on first review, and 4) the consultation of a third reviewer if there was still disagreement. Overall, of 288 reported endpoints, 30% required additional documentation or more than one review, and 16% were not confirmed at the end of the adjudication process. However, these percentages varied widely over different types of events. For example, of 30 reported nonophthalmalogic cytomegalovirus events, 37% required additional documentation and 40% were not confirmed. In contrast, every one of 17 reportedPneumocystis cariinipneumonias were confirmed with no requirement for additional documentation. The results can be used to help design endpoint documentation and adjudication procedures for other studies, thereby improving data quality and reducing costs.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundAntiretroviral therapy (ART) has resulted in reduced AIDS incidence and mortality. Socially marginalized individuals with HIV infection, particularly injection drug users (IDUs), have received less ART and derived less benefit than others. Little is known about the therapeutic process necessary to promote acceptance of and adherence to ART among marginalized HIV-infected populations. We report on the correlates of both acceptance of and adherence to ART among HIV infected prisoners, most of whom are IDUs.DesignUsing a cross-sectional survey design within four ambulatory prison HIV clinics, 205 HIV-infected prisoners eligible for ART were recruited between March and October 1996.MeasurementsDetailed interviews were conducted that included personal characteristics, health status and beliefs, and validated standardized scales measuring depression, health locus of control, social desirability and trust in physician, medical institutions and society. Acceptance and adherence were documented by self-report and validated for a subset by pharmacy review. Clinical information was obtained from standardized chart review. Adherence was defined as having taken ≥80% of ART.ResultsThe acceptance of (80%) and adherence to (84%) ART among this group of prisoners was high. Multiple regression models demonstrated that correlates of acceptance of and adherence to ART differed. Acceptance was associated with trust in physician (8% increase for each unit increase with trust in physician scale) and trust in HIV medications (threefold reduction for those mistrustful of medication). Side effects (OR = 0.09), social isolation (OR = 0.08), and complexity of the antiretroviral regimen (OR = 0.33) were associated with decreased adherence. The prevalence of health beliefs suggesting an adverse relationship between ART and drugs of abuse was high (range 59 to 77%). Adherence did not differ among those receiving directly observed therapy (82%) or self-administration (85%).ConclusionsART can be successfully administered within a correctional setting. Trust and the therapeutic relationship between patient and physician remain central in the ART initiation process. Characteristics of the therapeutic agents and the degree of social isolation predict adherence. These results may inform the design of interventions to improve both acceptance of and adherence to ART particularly among marginalized populations who have not derived full benefit from these potent new therapies.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo estimate HIV incidence, characterize correlates of HIV seroconversion, and monitor temporal trends in HIV transmission among patients repeatedly tested for HIV by a county hospital in San Francisco.DesignRetrospective longitudinal study.MethodsHIV incidence was retrospectively calculated among persons voluntarily tested for HIV antibody more than once at San Francisco's county hospital or one of its affiliated satellite community clinics between 1993 and 1999. Linkage of HIV test results in computerized databases identified “seroconverters” as individuals who had a negative antibody test followed by a positive test. The interval between tests was used as the person-time at risk. Cox proportional hazards analysis identified correlates of HIV seroconversion.ResultsA total of 84 HIV seroconversions were identified among 2893 eligible patients repeatedly tested for HIV antibody over a cumulative 5860 person-years (PYs) (incidence of 1.4 per 100 PYs, 95% confidence interval [CI]: 1.2–1.7). The majority of seroconversions (71 [84.5%]) were among injection drug users (IDUs) (incidence of 2.0 per 100 PYs, CI: 1.6–2.4). HIV incidence was highest among men who have sex with men (MSM) who were also IDUs (incidence of 3.8 per 100 PYs, CI: 2.7–5.1) and lowest among non-IDUs, heterosexual men, and non-IDU women (incidence of 0.3 per 100 PYs, CI: 0.1–0.6). In multivariate analysis, correlates of HIV seroconversion were age 25 to 29 years (hazard ratio [HR] = 3.9, CI: 2.4–6.3), MSM (HR = 2.9, CI: 1.9–4.4), and IDU (HR = 3.2, CI: 1.8–5.8). Overall, no temporal trend in annual HIV incidence was noted during the study period; however, HIV incidence among MSM IDUs increased from 2.9 per 100 PYs in 1996 to 4.7 per 100 PYs in 1998.ConclusionsThe rate of seroconversion in this hospital and affiliated clinic population is unexpectedly high. Moreover, HIV transmission among IDU patients has not decreased over the last several years. The San Francisco county hospital provides a high-risk sentinel population to monitor emerging trends in HIV transmission, especially among IDUs, and presents multiple opportunities for prevention interventions, because these patients are being seen repeatedly by clinicians.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo evaluate implementation of 1994 United States Public Health Service guidelines for zidovudine (ZDV) use in HIV-infected women and their newborns by describing the prevalence of use of perinatal ZDV and other antiretrovirals and by investigating determinants of not receiving perinatal ZDV.Design/MethodsThe Perinatal AIDS Collaborative Transmission Study is a prospective cohort study designed to collect information related to mother-to-child HIV transmission that was conducted in New York City (NY), Newark (NJ), Baltimore (MD), and Atlanta (GA), U.S.A. The current analysis was restricted to infants born between July 1994 and June 1998.ResultsUtilization rates for antenatal, intrapartum, and neonatal ZDV increased from 41% to 70% during the 4-year period. Use of combination antiretrovirals increased from fewer than 2% of women in 1994 to 1995 to 35% in 1997 to 1998. Antenatal and neonatal ZDV use increased each year, but intrapartum ZDV use reached a plateau after 1996. Mother-infant pairs with the following characteristics were less likely to have received a complete 3-part ZDV regimen: older maternal age, CD4 count >500 cells/&mgr;l, preterm birth, cocaine or heroin use during pregnancy, positive newborn drug screen test result, and smoking or alcohol use during pregnancy. By multivariate logistic regression adjusted for hospital and year of birth, cocaine or heroin use during pregnancy (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6–3.3), maternal CD4 count (OR, 0.4; 95% CI, 0.2–0.8; comparing <200 with >500 cells/&mgr;l), and preterm birth (OR, 1.6; 95% CI, 1.1–2.5) remained independently associated with not receiving the complete ZDV regimen.ConclusionsZDV use by pregnant HIV-infected women and their infants has increased dramatically since publication of the 1994 guidelines. Nevertheless, women who abuse substances, give birth preterm, or have less advanced immunosuppression, were at substantial risk of not receiving the complete ZDV regimen.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID