Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: ZK856 .18
48,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the association between two components of the Health Belief Model (perceived vulnerability and barriers) and adherence to antiretroviral therapy (ART) among children who are HIV-infected. The parents/caregivers of 30 children (mean age = 5.21, SD = 3.18) who were HIV-infected and who were on active ART were surveyed to assess current methods of adherence assessment and educational efforts within the institution. All participants (except one) were African American and reported low monthly family incomes (M = $869.45, SD = $832.63). Assessment instruments included measures of perceived vulnerability, caregiver-reported adherence and perceived barriers, and objective measures of adherence (clinical pill count; electronic measurement). The results failed to demonstrate a significant relationship between parental perceived vulnerability, perceived barriers and adherence to antiretroviral medications. Methods of assessing adherence provided significantly discrepant estimates of adherence. Results are discussed in terms of implications for patient care and for future research in this area. The addition of behavioural and motivational components to traditional educational approaches may positively impact treatment results.
...
PMID:Adherence to antiretroviral therapy among HIV-positive children: examination of the role of caregiver health beliefs. 1157 Oct 8

The membrane-proximal tryptophan-rich region of the HIV transmembrane glycoprotein, gp41, plays an important role in the membrane fusion reaction. Using NMR spectroscopy, we have studied the tertiary structure of a synthetic 19-residue amidated peptide (NH2-KWASLWNWFNITNWLWYIK-CONH2) corresponding to this region in membrane-mimetic environments. Initial experiments in sodium dodecyl sulfate/H2O micelles and trifluoroethanol gave poor results, because of low solubility. However, in dodecylphosphocholine micelles, we obtained excellent 500 and 800 MHz NMR spectra, suggesting that the peptide has a preference for a zwitterionic membrane-like environment. The final NMR structures demonstrated a well-defined helical peptide with a backbone rmsd of 0.47 +/- 0.18 A. Four of the five tryptophan residues, as well as the tyrosine residue, formed a "collar" of aromatic residues along the axial length of the helix. By analogy to related tryptophan-rich antimicrobial peptides, the structure indicates that the aromatic residues of the HIV peptide are positioned within the membrane-water interface of a phospholipid bilayer. This is confirmed by the observation of direct NOEs between the aromatic residues of the peptide to the headgroup and interfacial protons of prototonated dodecylphosphocholine. The bulk of the polar residues are positioned on one face of this structure, with the hydrophobic phenylalanine side chain on the opposing face, forming an amphipathic structure. This work shows that the Trp-rich membrane-proximal region of HIV and related viruses can bind to the surfaces of zwitterioninc membranes in a "Velcro-like" manner.
...
PMID:The membrane-proximal tryptophan-rich region of the HIV glycoprotein, gp41, forms a well-defined helix in dodecylphosphocholine micelles. 1158 56

The objective of this study was to develop and validate a method for estimating and monitoring over time the transmission rate of vertically acquired HIV infection at the population level. We estimated the annual number of children born to HIV-infected women in Italy in 1991-1994 by multiplying the seroprevalence rates, provided by Anonymous Unlinked HIV Serosurveys among Italian Newborns, by the annual number of births, provided by the Italian National Institute of Statistics. The number of HIV-infected children was estimated by applying a simplified back-calculation method to the incident cases of vertically acquired AIDS reported to the AIDS surveillance registry, using seven different estimates of the distribution of the incubation period identified through a literature search. The annual vertical transmission rates were estimated by dividing the estimated number of children with vertically acquired HIV infection by the estimated number of births to an HIV-infected mother. Depending on the chosen distribution of the incubation period, the estimated transmission rate for the four-year period ranges from 0.10 to 0.30. Five of the seven incubation distributions provided a rate falling within the very narrow interval 0.18-0.20. The method provided estimates of vertical transmission rates consistent with those of longitudinal studies performed in European countries. The method presented here could be useful for monitoring the impact of interventions aimed at reducing HIV vertical transmission rate.
...
PMID:Monitoring the trend of the transmission rate of vertically acquired HIV infection: a simple method applied to Italian data. 1169 29

The combination of rifabutin and ciprofloxacin is potentially useful for the treatment of disseminated Mycobacterium avium-intracellulare (MAC) diseases in HIV-infected patients. Rifabutin is a metabolic enzyme inducer structurally similar to its predecessor, rifampin. Using a mouse model, the effects of repeated exposure of rifabutin on the pharmacokinetics of ciprofloxacin after intravenous (i.v.) and oral (p.o.) dosing were investigated in the present study. Results showed that repeated exposure of rifabutin, relative to control, caused a 16% increase in the plasma clearance (CL) of ciprofloxacin after i.v. dosing (4.19 vs. 4.87 L/h/kg). Estimates of elimination half-life (T1/2) were not affected by rifabutin (control: 0.81 vs. rifabutin pretreated: 1.18 h). The data obtained after oral dosing showed that repeated rifabutin dosing caused a significant reduction in the maximal plasma concentration (Cmax: 1.34 vs. 0.91 microg/mL) and a longer time to Cmax (Tmax: 0.17 vs. 0.33 h). These changes might be in part attributable to the increase in oral clearance (CL/F) by 18%. With or without rifabutin pretreatment, the T1/2 estimates of ciprofloxacin for p.o. dosing were similar (2.37-2.58 h) and were approximately twice as long as those obtained after i.v. dosing. Since the changes in systemic exposure as a result of rifabutin pretreatment were similar after i.v. and p.o. dosing, the oral bioavailability (F) of ciprofloxacin remained unaffected by rifabutin at approximately 38%. The effects of rifabutin on the pharmacokinetics of ciprofloxacin appear to be moderate in the mouse model which might be attributable to the absorption and distribution behavior of the quinolone antibiotic. The therapeutic implications of this interaction, if any, remain to be defined.
...
PMID:Effects of repeated rifabutin administration on the pharmacokinetics of intravenous and oral ciprofloxacin in mice. 1176 Feb 22

To better characterize the somatotropic axis in HIV-infected children the circadian rhythm of growth hormone (GH), and basal and stimulated (by an insulin-like growth factor I [IGF-I] generation test) plasma levels of IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3), were evaluated in 16 children (9 boys and 7 girls; age range, 7-11 years) with HIV infection. All patients were free from active opportunistic infection or liver disease at the time of the study. Sixteen age- and sex-matched healthy children (10 boys and 6 girls; age range, 7-11 years) served as control subjects. GH rhythmometric data were analyzed by single and population mean cosinor analysis. As regards the IGF-I generation test, biosynthetic human GH (hGH, 0.1 IU/kg, 0.033 mg/kg) was administered subcutaneously for 4 days and blood samples were taken from fasting subjects at baseline and on the morning after the last GH injection for measurement of IGF-I and IGFBP-3. Plasma GH levels fell within normal limits in the HIV-seropositive patients and were similar to those of healthy children (1.31 +/- 1.18 vs. 1.57 +/- 1.16 microg/liter, respectively; mean +/- SD). The population mean cosinor analysis shows that the GH circadian rhythm reached statistical significance both in the HIV-seropositive children and in the control group. Despite this, the IGF-I and IGFBP-3 levels were significantly lower in HIV-infected children than in the control group (75.6 +/- 57.2 vs. 233.3 +/- 52.5 ng/ml, p < 0.001 and 2.09 +/- 0.17 vs. 3.89 +/- 0.24 mg/liter, p < 0.01, respectively; mean +/- SD); moreover, the response of IGF-I and IGFBP-3 to the IGF-I generation test was significantly lower in HIV-infected children than in the control group (86.3 +/- 55.8 vs. 257.5 +/- 53.4 ng/ml, p < 0.001 and 3.14 +/- 0.43 mg/liter, p < 0.01, respectively; mean +/- SD). It appears that circadian GH secretion is normal in children with HIV infection, but the response to exogenous GH with regard to IGF-I and IGFBP-3 production is impaired, indicating a degree of GH insensitivity in such children.
...
PMID:Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 response to growth hormone is impaired in HIV-infected children. 1189 34

This meta-analysis summarizes the broad spectrum of neuropsychological research on HIV disease across a sample of 41 primary studies and an aggregate of 8,616 participants for 10 major neuropsychological ability areas. Analyses of the course of cognitive decline within and across Centers for Disease Control classifications reveals statistically significant cognitive deficits from asymptomatic HIV to AIDS. Effect sizes (Cohen, 1988) were calculated to reflect between-group (asymptomatic, symptomatic, AIDS) differences in each neuropsychological domain. Relatively small effect sizes were obtained for the asymptomatic (0.05-0.21) patients, and generally small to moderate effect sizes were obtained for symptomatic (0.18-0.65) HIV+ patients, with motor functioning exhibiting the greatest effects in this later disease stage. The most notable deficits in cognitive functioning were found in the AIDS group with moderate (attention and concentration) to large (motor functioning) effect sizes with values ranging from 0.42-0.82. Comparison of cognitive functioning as a function of disease progression revealed that motor functioning, executive skills, and information processing speed were among the cognitive domains showing the greatest decline from early to later stages of HIV. These findings indicate that cognitive deficits in the early stages of HIV are small and increase in the later phases of the illness, and that specific patterns of cognitive deficits can be detected with disease progression. These results and their clinical utility are further discussed.
...
PMID:A meta-analysis of the neuropsychological sequelae of HIV infection. 1193 99

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 (C(min)) were measured at 1 and 7 days of age. Intensive pharmacokinetic evaluations were performed at 14 and 28 days of age. The median NFV C(min) values 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.
...
PMID:Dose-escalating study of the safety and pharmacokinetics of nelfinavir in HIV-exposed neonates. 1198 61

To estimate the effect of behavioral and social interventions on sexual risk of HIV among sexually experienced adolescents in the United States and to assess factors associated with variation in outcomes, we selected studies from the HIV/AIDS Prevention Research Synthesis project database. Twenty studies published or reported during the years 1988 through 1998 met criteria: 16 presented sufficient data; of these, 15 evaluated behavioral interventions and 1 a social intervention. Summary odds ratios (ORs) and 95% confidence intervals (CIs), weighted by study precision, indicated significantly less sex without condoms (number of studies, k, 13; OR, 0.66; CI, 0.55-0.79) and lower behavioral risk (k, 2; OR, 0.66; CI, 0.50-0.88), but no difference in number of partners (k, 8; OR, 0.89; CI, 0.76-1.05) or STDs (k, 2; OR, 1.18; CI, 0.48-2.86). A composite sexual risk behavior variable (k, 16; 1 outcome per study; preferred order, sex without condoms, number of partners, risk index) was used for heterogeneity and publication bias tests and stratified analyses. Overall, these interventions had a significant protective effect on sexually experienced adolescents (k, 16; OR, 0.65; CI, 0.50 - 0.85), although there was a suggestion of publication bias. Study design and intervention variables did not explain outcome variation. An exploratory finding may merit investigation: interventions tested with single ethnic groups out-of-class (k, 5) had larger effects than in-class interventions with mixed ethnic groups (k, 11), whether the mixed groups were in- (k, 6) or out-of class (k, 5).
...
PMID:Meta-analysis of the effects of behavioral HIV prevention interventions on the sexual risk behavior of sexually experienced adolescents in controlled studies in the United States. 1210 63

This study provides population-based estimates of the incidence of constituent symptoms associated with HIV-related lipodystrophy syndrome. Possible predictors of symptomatology based on analysis of accrued cases are provided after adjustment for a broad range of personal, clinical, and treatment characteristics. Patients enrolled in a province-wide HIV/AIDS treatment program reported annually on the occurrence of lipoatrophy, lipohypertrophy, and elevated triglyceride and cholesterol levels. Of 1261 individuals who provided baseline data, 745 were available at follow-up, among whom incidence was 27% for lipoatrophy, 21% for lipohypertrophy, and 10% and 16% for increased triglyceride and cholesterol levels, respectively. In logistic multivariate modeling, incident lipoatrophy was associated with duration of stavudine (per quarter) (adjusted odds ratio [AOR] 1.18; 95% confidence interval [CI] 1.09-1.27) and having been diagnosed with AIDS (AOR 2.07; 95% CI 1.20-3.56). Lipohypertrophy risk increased with use of protease inhibitor (AOR 3.53; 95% CI 1.81-6.86) and stavudine (AOR 3.67; 95% CI 1.61-8.38). Incident cholesterol or triglyceride abnormalities were associated with protease inhibitor use (AOR 7.17; 95% CI 2.46-20.96) and duration of ritonavir (per quarter) (AOR 1.12; 95% CI 1.04-1.21). Our findings suggest high annual rates of incidence and a role of first line antiretroviral therapies in symptom development. These outcomes, in conjunction with the findings of others have important implications for evolving treatment patterns.
...
PMID:Antiretroviral treatment patterns and incident HIV-associated morphologic and lipid abnormalities in a population-based chort. 1213 51

Heterogeneity in genotype mutations associated with resistance of HIV to nonnucleoside reverse transcriptase inhibitors (NNRTIs) should allow identification of patients failing nevirapine (NVP) who might benefit from efavirenz (EFV)-containing salvage regimens. To establish the feasibility of recycling EFV after failure of NVP-containing regimens genotypic data on 103 NVP-failed patients were analyzed to evaluate the prevalence of EFV resistance-conferring mutations. A clinically significant resistance to EFV was found in 50 of 103 (58%) of NVP-failed subjects. Furthermore, the 3-month virological response to salvage regimens containing EFV was assessed in patients previously treated with NVP and carrying single mutations conferring resistance to this drug. A proportion of HIV RNA less than 500 copies/ml at 3 months was obtained only in 2 of 12 (17%) of EFV-treated subjects compared with 35 of 67 (52%) of those without NNRTI mutations (OR, 0.18; 95% CI, 0.03-0.79). The median HIV-1 RNA decrease after 3 months was -0.63 log(10) among patients carrying single NNRTI-associated mutations compared with -1.32 log(10) among those without any NNRTI mutations. No virological response was observed in six patients harboring a single Y181C/I mutation. On the basis of the present data, sequential use of NNRTIs should be avoided in the management of treatment failure.
...
PMID:Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure. 1220 5


<< Previous 1 2 3 4 5 6 7 8 9 10