scholarly journals Association between social psychological status and efavirenz and nevirapine plasma concentration among HIV patients in Kenya

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Musa Otieno Ngayo ◽  
Margaret Oluka ◽  
Wallace Dimbuson Bulimo ◽  
Faith Apolot Okalebo
Keyword(s):  
Social Support ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Significant Proportion ◽  
Psychological Status ◽  
Hiv Positive ◽  
Social Psychological ◽  
Hiv Patients ◽  
Quantile Regression Analysis ◽  
Multivariate Quantile

AbstractHIV-related stigma, lack of disclosure and social support are still hindrances to HIV testing, care, and prevention. We assessed the association of these social-psychological statuses with nevirapine (NVP) and efavirenz (EFV) plasma concentrations among HIV patients in Kenya. Blood samples were obtained from 254 and 312 consenting HIV patients on NVP- and EFV-based first-line antiretroviral therapy (ART), respectively, and a detailed structured questionnaire was administered. The ARV plasma concentration was measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). There were 68.1% and 65.4% of the patients on NVP and EFV, respectively, who did not feel guilty for being HIV positive. The disclosure rates were approximately 96.1% and 94.6% of patients on NVP and EFV, respectively. Approximately 85% and 78.2% of patients on NVP and EFV, respectively, received social support as much as needed. There were 54.3% and 14.2% compared to 31.7% and 4.5% patients on NVP and EFV, respectively, with supratherapeutic and suboptimal plasma concentrations. Multivariate quantile regression analysis showed that feeling guilty for being HIV positive was associated with increased 954 ng/mL NVP plasma concentrations (95% CI 192.7 to 2156.6; p = 0.014) but not associated with EFV plasma concentrations (adjusted β = 347.7, 95% CI = − 153.4 to 848.7; p = 0.173). Feeling worthless for being HIV positive was associated with increased NVP plasma concentrations (adjusted β = 852, 95% CI = 64.3 to 1639.7; p = 0.034) and not with EFV plasma concentrations (adjusted β = − 143.3, 95% CI = − 759.2 to 472.5; p = 0.647). Being certain of telling the primary sexual partner about HIV-positive status was associated with increased EFV plasma concentrations (adjusted β 363, 95% CI, 97.9 to 628.1; p = 0.007) but not with NVP plasma concentrations (adjusted β = 341.5, 95% CI = − 1357 to 2040; p = 0.692). Disclosing HIV status to neighbors was associated with increased NVP plasma concentrations (adjusted β = 1731, 95% CI = 376 to 3086; p = 0.012) but not with EFV plasma concentrations (adjusted β = − 251, 95% CI = − 1714.1 to 1212.1; p = 0.736). Obtaining transportation to the hospital whenever needed was associated with a reduction in NVP plasma concentrations (adjusted β = − 1143.3, 95% CI = − 1914.3 to − 372.4; p = 0.004) but not with EFV plasma concentrations (adjusted β = − 6.6, 95% CI = − 377.8 to 364.7; p = 0.972). HIV stigma, lack disclosure and inadequate social support are still experienced by HIV-infected patients in Kenya. A significant proportion of patients receiving the NVP-based regimen had supra- and subtherapeutic plasma concentrations compared to EFV. Social-psychological factors negatively impact adherence and are associated with increased NVP plasma concentration compared to EFV.

scholarly journals Influence of Social Psychological Status On Efavirenz And Nevirapine Plasma Concentration Among HIV Patients In Kenya

2021 ◽  
Author(s):  
Musa Otieno Ngayo ◽  
Margaret Oluka ◽  
Wallace Dimbuson Bulimo ◽  
Faith Apolot Okalebo
Keyword(s):  
Social Support ◽  
Plasma Concentration ◽  
Plasma Level ◽  
Median Duration ◽  
Viral Suppression ◽  
Linear Regression Analysis ◽  
Psychological Status ◽  
Hiv Positive ◽  
Multivariate Linear Regression Analysis ◽  
Hiv Patients

Abstract HIV-related stigma, lack of disclosure and social support are still a hindrance to HIV testing, care, and prevention. We evaluated the influence of these socio-phycological status on nevirapine (NVP) and efavirenz (EFV) plasma concentrations among HIV patients in Kenya. Blood samples were obtained from 254 and 312 consenting HIV patients on NVP and EFV based first-line Antiretroviral therapy (ART) respectively and a detailed structured questionnaire was administered. The NVP and EFV plasma level was measured by liquid chromatography - tandem mass spectrometry (LC-MS/MS). The median duration of living with HIV infection was 5 years (IQR = 1–11years) and a median duration since ART initiation was 3 years (IQR = 1–8 years). There were 68.1% and 65.4% of the patients on NVP and EFV respectively who did not feel guilty for being HIV positive. The disclosure rate was about 96.1% and 94.6% of patients on NVP and EFV respectively. About 85% and 78.2% of patients on NVP and EFV respectively who got social support as much as needed. The non-adherence to ART in the past 30 days was 64.6% and 66.3% patients on NVP and EFV respectively. The median (IQR) plasma concentration were [6237.5 ng/mL, IQR 45188–8964 ng/mL] for NVP and [2739.5 ng/mL, IQR 1878 –4891.5 ng/mL] for EFV. There were 14.2% and 4.5% patients on NVP and EFV respectively with suboptimal plasma concertation associated with poor viral suppression. Multivariate linear regression analysis showed feeling guilty for being HIV positive (adjusted β = 954, 95% CI = 192.7 to 2156.6; p =0.014) or feeling worthless for being HIV positive (adjusted β = 852, 95% CI = 64.3 to 1639.7; p =0.034); being certain of telling the primary sexual partner about HIV positive status (adjusted β 363, 95% CI, 97.9 to 628.1; p = 0.007); disclosing HIV status to neighbors (adjusted β = 1731, 95% CI = 376 to 3086; p =0.012) and getting transportation to hospital whenever needed (adjusted β = -1143.3, 95% CI = -1914.3 to -372.4; p =0.004) were associated with NVP/EFV plasma levels. The NVP and EFV plasma level was highly heterogenous with a significant proportion of patients reporting levels correlated with poor viral suppression. The patient’s stigma, lack of disclosure and social support contributes significantly on the overall ART treatment outcome. Taking these factors into consideration, HIV treatment may be personalized to achieve optimal treatment success

Lack of Medical Support in HIV Infection and Unstable Mood States

1997 ◽  
Vol 81 (2) ◽  
pp. 635-639
Author(s):  
Motoko Hayashi ◽  
Isao Fukunishi
Keyword(s):  
Social Support ◽  
Depressive Symptoms ◽  
Major Depression ◽  
Hiv Infection ◽  
Mood Disorders ◽  
Early Stage ◽  
Mood States ◽  
Hiv Positive ◽  
Medical Support ◽  
Hiv Patients

This study examined what kinds of social support are related to mood states in a sample of 50 HIV-positive patients without AIDS (46 men and 4 women; M age 36.5 yr., SD = 9.8). In the early stage of HIV infection, HIV patients without AIDS may be prone to depressive symptoms although none of these HIV-positive patients' symptoms fulfilled the DSM-III-R Mood Disorders including Major Depression. The depressive symptoms were not significantly related to lack of ordinary social support such as friends and family but were significantly associated with dissatisfaction with HIV/AIDS-related medical support

Alexithymic Characteristics of HIV-Positive Patients

1999 ◽  
Vol 85 (3) ◽  
pp. 963-970 ◽  
Author(s):  
Isao Fukunishi ◽  
Naotsugu Hirabayashi ◽  
Tomoko Matsumoto ◽  
Kyoko Yamanaka ◽  
Katsuyuki Fukutake
Keyword(s):  
Social Support ◽  
Hiv Infection ◽  
Stress And Coping ◽  
Psychiatric Research ◽  
Hiv Positive ◽  
Healthy Controls ◽  
Hiv Patients ◽  
Related Factors ◽  
The Social ◽  
And Coping

Despite extensive psychiatric research on HIV-positive patients, there are no published studies on alexithymia. Alexithymic characteristics and related factors were examined in a sample of 81 HIV-positive patients using the modified Beth Israel Psychosomatic Questionnaire and the Social Support of Stress and Coping Inventory. The seventy of alexithymia was significantly higher in HIV patients than healthy controls, suggesting the presence of secondary alexithymia Scores on two alexithymic characteristics, affect awareness and operational thinking, significantly correlated with ratings of poor utilization and perception of social support. As the severity of HIV infection progressed, affect awareness was higher, controlling for poor utilization and perception of social support. These results suggest that secondary alexithymia, associated with poor utilization and perception of social support, may be manifest as a state reaction to approaching death.

Generalized mycobacteriosis with secondary lesions of the spine in HIV positive patients

MedAlliance ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 54-60
Keyword(s):  
Antibiotic Therapy ◽  
Granulomatous Inflammation ◽  
Hiv Positive ◽  
Hiv Patients ◽  
Histological Picture ◽  
Clinical Observations ◽  
Spinal Lesion ◽  
Secondary Lesion

2 clinical observations of generalized forms of mycobacteriosis in HIV (+) patients complicated by secondary spinal lesion are described. Anamnestic data on the presence of mycobacteriosis of the lungs allowed to suspect a secondary lesion of the spine. Verification of the diagnosis is possible only with bacteriological confirmation, since the histological picture is nonspecific and resembles tuberculous granulomatous inflammation. Treatment of spondylitis caused by non-tuberculous mycobacteria is complex and includes both surgical rehabilitation of the focus and long-term (at least 1 year) antibiotic therapy.

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

Effects of diltiazem on atrioventricular conduction and arterial blood pressure: correlation with plasma drug concentrations

1984 ◽  
Vol 62 (12) ◽  
pp. 1479-1486 ◽  
Author(s):  
Jean-Paul Clozel ◽  
Jacques Billette ◽  
Gilles Caillé ◽  
Pierre Théroux ◽  
Richard Cartier
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Refractory Period ◽  
Plasma Concentrations ◽  
Atrioventricular Conduction ◽  
Gas Liquid Chromatography ◽  
Conduction Time ◽  
Arterial Blood ◽  
Drug Concentrations ◽  
Atrial Conduction Time

Atrial and atrioventricular conduction variables were studied at control and at the end of each of six consecutive 45-min diltiazem administration periods in eight closed chest-anesthetized dogs. Diltiazem was given as a bolus (50 μg/kg, i.v.) followed by an infusion (0.5 μg∙kg−1∙min−1); doses were doubled in subsequent periods. The plasma concentrations, measured by gas–liquid chromatography, ranged from 8 to 1400 ng/mL and correlated strongly with the doses (r = 0.92; p < 0.01). The Wenckebach cycle length, basic conduction time, and functional refractory period of the atrioventricular (AV) node increased proportionally with plasma concentration (respective r = 0.90, 0.89, 0.80; p < 0.01). The minimum mean plasma concentrations affecting these variables significantly were 37, 83, and 175 ng/mL, respectively. Second or third degree AV blocks developed in all dogs for plasma concentrations between 379 and 1400 ng/mL. In four dogs which were given isoproterenol (0.2 μg∙kg−1∙min−1), these blocks disappeared within 1 min. Atrial conduction time and functional refractory period were slightly but significantly shortened by diltiazem with mean plasma concentrations of 175 ng/mL and over. His–Purkinje intervals were not significantly changed by diltiazem. Systolic and diastolic arterial pressures were decreased by diltiazem (r = −0.64, r = −0.79; p < 0.01) starting with a mean plasma concentration of 83 ng/mL. We conclude that AV nodal conduction variables are progressively prolonged with increasing plasma concentrations of diltiazem; plasma concentrations affecting blood pressure and AV nodal variables overlap; and the AV blocks produced by toxic concentrations of diltiazem can be corrected by isoproterenol.

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