Objective: To generate insights into the mechanism of NVP induced hepatotoxicity. Methods: Liver(HepG2) cells were cultured with various concentrations of NVP. This cell line was chosen because it has low expression o...Objective: To generate insights into the mechanism of NVP induced hepatotoxicity. Methods: Liver(HepG2) cells were cultured with various concentrations of NVP. This cell line was chosen because it has low expression of cytochrome P450, allowing evaluation of the effects of NVP rather than specific metabolites. Cytotoxicity was determined using a proliferation assay and cell numbers were monitored using trypan blue exclusion assay for long term culture experiments and apoptosis induction was determined by morphological and biochemical investigation. Results: HepG2 cells treated with the highest concentration of NVP tested(819 μM) initially showed a rounded morphology and all cells had died by week three of exposure. Nuclear condensation and fragmentation, increased Annexin V/propidium iodide staining and caspase 9 activation all supported the induction of apoptosis in HepG2 cells in response to NVP treatment. Conclusions: There is a clear induction of apoptosis in response to NVP which suggests that NVP has significant cytotoxicity, over and above any cytotoxicity of metabolites and may contribute directly to patient hepatotoxicity.展开更多
Background: There are two approved non-nucleoside reverse transcriptase inhibitor antiretroviral drugs;namely Nevirapine (NVP) and Efavirenz (EFV). Nevirapine and EFV have comparable clinical efficacy when administere...Background: There are two approved non-nucleoside reverse transcriptase inhibitor antiretroviral drugs;namely Nevirapine (NVP) and Efavirenz (EFV). Nevirapine and EFV have comparable clinical efficacy when administered in combination regimens. But there is a lack of recent evidence showing the effect of NVP and EFV-based ARTs on immunological responses in HIV infected individuals in Ethiopia in general and Addis Ababa in particular. Methods: Retrospective cohort study design was used to compare immunological response rate of NVP and EFV based HAART regimen in Addis Ababa. Four hundred ninety two HIV infected patients who started HAART in ten selected health facilities were included in the study. Rate of immunologic response was examined at the 6th, 12th, 18th, and 24th months of follow-up period. The time required to get immunological response was analyzed by Kaplan-Meier survival curve. Adjusted hazard ratio was calculated with a 95% confidence interval by Cox proportional hazards model to determine the rate of immunological response. To ascertain the association, bivariate and multi variable Cox proportional hazard model was used. Statistical significance was considered with two sides P-value of 0.05. Results: The mean CD4 count ranged between 132.2 cell/μl at baseline and 302.3 cell/μl at the end of the follow-up period. This change was significant at 95% of CI but did not show significant differences among the comparison group. The median time to get immunological response was 18 (75% percental 12) months. At the end of the follow-up period, 73.2% (76.6% for NVP and 69.8% for EVF P-value 0.13) of the study population had immunological response. Conclusion: As a conclusion, there was a robust and sustained CD4 response and the effect of NVP and EFV based ART on change of mean CD4 count and immunological response was comparable and effective. Initiation of ART with high baseline CD4 count, in combination of IPT and with either NVP or EFV based NNTI was recommended.展开更多
Background: Over 90% of infection in children is acquired through mother to child transmission (MTCT). Nevirapine’s efficacy, safety and affordable cost make it the most preferred non-nucleoside reverse transcriptase...Background: Over 90% of infection in children is acquired through mother to child transmission (MTCT). Nevirapine’s efficacy, safety and affordable cost make it the most preferred non-nucleoside reverse transcriptase inhibitor (NNRTI) for paediatric prophylactic use in resource limited settings. There are very few studies on pediatric adherence to antiretroviral prophylaxis, especially in very young infants. The objective of the study was to evaluate the adherence to nevirapine for prevention of mother to child transmission (PMTCT) amongst infants of HIV positive mothers in the first 6 weeks of life. Methods: This was a questionnaire based prospective cross-sectional multicenter study initiated in July 2015 and concluded in December 2017. The study was carried out at the Aids Prevention in Nigeria (APIN/HIV) human immunodeficiency paediatric clinics of the Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos State, 68 Nigerian Army Reference Hospital Yaba (68NARHY) Lagos, Nigeria and the Holy Family Catholic Hospital, Festac Town, Amuwo Odofin, Lagos State. Nevirapine adherence, in infants of 0 - 6 weeks was measured by maternal verbal reports. Results: Eighty-one (81) infants receiving nevirapine within the age of 0 - 6 weeks completed the study. Majority of the infants started treatment at birth (32%) and after 4 weeks (31%). 54% of the 81 respondents do not miss or skip their doses while 46% of respondents skip doses. Majority of the respondents 18 (49%) missed their doses for 24 - 48 hours while 25% missed their doses because they were away from home and 23% ran out of pills. 85.2% took ≥95% of the prescribed medications (good or high adherence ), 8.2% took 80% - 95% of doses (moderate adherence) while 6.2% took 0.05). Conclusions: The adherence rates found in this study are comparable to other studies in developing countries. But these rates are still low for good clinical outcomes. Different levels of adherence were documented with the majority having good or high adherence. Not all of the infants started treatment at birth and Institutional delivery should be encouraged to improve early initiation of prophylaxis. The finding of patients with low adherence rates among the study population calls for intensification of counselling on adherence and should continue to be an integral part of prevention of mother to child transmission. Improved access to antiretroviral agents and improved care delivery systems are important.展开更多
A Novel stability indicating RP-UPLC chromatographic method was developed for analysis of Nevirapine in pharmaceutical formulations. The developed RP-UPLC method is superior in technology to conventional RP-HPLC with ...A Novel stability indicating RP-UPLC chromatographic method was developed for analysis of Nevirapine in pharmaceutical formulations. The developed RP-UPLC method is superior in technology to conventional RP-HPLC with respect to speed, resolution, solvent consumption and cost of analysis. Nevirapine was subjected to the stress conditions like acid, base, thermal, oxidative and photolytic degradation. Nevirapine was found to degrade significantly in acid and thermal degradation. In acid degradation relative retention time with 0.42 is found as unknown impurity. New impurity was identified, isolated using mass based auto purification system and characterized by <sup>1</sup>H NMR (<sup>1</sup>D and <sup>2</sup>D) and HRMS experiments. Isolated impurity was showing molecular weight of 244.10, molecular formula C<sub>12</sub>H<sub>12</sub>N<sub>4</sub>O<sub>2</sub> and its name as 2-(3-Amino-4-methylpyridin-2-ylamino)nicotinic acid. The calibration graph was linear and the method showed less deviation in accuracy results. The test solution was found to be stable for 20 days when stored in the refrigerator between 2°C to 8°C. The developed RP-UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines. The intra-day and inter-day variation was less than 1%. The method was reproducible and selective for the estimation of Nevirapine. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating method.展开更多
Transdermal drug delivery not only has contributed immensely to medical practice, but has enjoyed enormous interest in the field of cosmetic and pharmaceutical industries. Nevirapine, a non‐nucleoside reverse transcr...Transdermal drug delivery not only has contributed immensely to medical practice, but has enjoyed enormous interest in the field of cosmetic and pharmaceutical industries. Nevirapine, a non‐nucleoside reverse transcriptase inhibitor (NNRTI) is used clinically for the treatment of HIV‐ 1 infection. The aim of the present study is to investigate the influence of cosolvents (glycerol, propylene glycol, ethanol, polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80, sodium lauryl sulfate, sodium cholate and cetrimide) on the dermal permeability coefficient of nevirapine by utilizing established and recognized mathematical model that employs partition coefficient as one of its molecular descriptors. The partition coefficient of nevirapine is determined in chloroform-water system at room temperature using the shake flask method. The results show that all the cosolvents used in this study decrease the partition coefficient of nevirapine. The same decrease in the partition coefficient of nevirapine is observed with all the surfactants investigated. The order of dermal enhancement potential of the vehicles studied based on the predicted permeability coefficient is glycerol > propylene glycol > ethanol > polyethylene glycol 400 for the cosolvents while tween 20 > tween 80 > sodium lauryl sulfate > sodium cholate > cetrimide for the surfactants. The maximum predicted flux through skin was obtained by multiplying the predicted permeability coefficient and the drug aqueous solubility. As the rate of penetration into the skin is quantitatively assessed by the use of permeability coefficient, the findings suggest that for dermal formulation of nevirapine, glycerol and tween 20 are the most preferred vehicles out of the vehicles investigated. Furthermore, the results of the correlation coefficients obtained by plotting permeability coefficient or maximum predicted flux, versus logarithm partition coefficient indicate that permeability coefficient can be a more reliable parameter to predict transdermal absorption of nevirapine than flux.展开更多
The development of the spectrofluorimetric method can be considered a promising alternative that is relatively less expensive and sufficiently reliable. In the current literature, no method for the analysis of nevirap...The development of the spectrofluorimetric method can be considered a promising alternative that is relatively less expensive and sufficiently reliable. In the current literature, no method for the analysis of nevirapine by spectro-fluorimetric has been reported. The proposed method is based on the transformation of naturally non-fluorescent nevirapine into a fluorescent derivative after chemical synthesis. Maximum excitation and emission wavelengths are 290 nm and 357 nm respectively. The analytical performance of the method demonstrates linearity in the concentration range 1.5 × 10<sup>-2</sup> and 13.5 × 10<sup>-2</sup> μg/mL with a correlation coefficient (r) greater than 0.999. The detection (LOD) and quantification (LOQ) limits found are 1.97 × 10<sup>-3</sup> μg/mL and 5.48 × 10<sup>-3</sup> μg/mL respectively. Recovery is achieved with 99.9% and 100.3% trueness, intra-day precision with a coefficient of variation of repeatability (CVr) of 0.99% and inter-day precision with a coefficient of variation of precision (CVR) of 1.7%. The method has been successfully applied in the analysis of 10 batches of nevirapine tablets and suspensions.展开更多
The Nevirapine (NVP)/Polycaprolactone (PCL)/Nanoparticles hybrids systems have been developed as a potential platform for drug delivery, by solvent cast, as thin films. NVP, an antiretroviral drug, was included within...The Nevirapine (NVP)/Polycaprolactone (PCL)/Nanoparticles hybrids systems have been developed as a potential platform for drug delivery, by solvent cast, as thin films. NVP, an antiretroviral drug, was included within PCL matrix containing three types of nanoparticles: an organoclay layered silicate Viscogel S7®(3% w/w), hydrophilic silica oxide particles Aerosil®A20 (0.25% w/w) and titanium dioxide particles (0.25% w/w). These systems were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), low-field nuclear magnetic resonance (NMR), ultraviolet-visible spectroscopy (UV), in-vitro dissolution testing and drug release mechanism kinetics. The PCL crystallization was affected by NVP incorporation, modifying its semi-crystalline structure to a less ordered structure. When nanoparticles and NVP were added, the T<sub>1</sub>H values increased, for PCL, PCL/S7, PCL/ SiO<sub>2</sub> and PCL/TiO<sub>2</sub> hybrids, suggesting that its addition produced a new material, with less molecular mobility, due to the new intermolecular interactions formation. It can consider a structure formation among the PCL chains, nanoparticles and NVP, with strong forces in the PCL/SiO<sub>2</sub>/NVP system. The amount of NVP included was around 1.5 ± 0.03 mg/cm<sup>2</sup>. In the in-vitro dissolution test, the PCL/SiO<sub>2</sub>/NVP system released the smallest amount of drug and this result could be attributed to the strong intermolecular interaction between the drug and the PCL/SiO<sub>2</sub> system. Higuchi’s model was the mathematical model chosen to treat the release data, since this model presented the highest coefficient correlation (r) value. The drug release probably occur by diffusion through the matrix pores, thus, these materials are suitable for sustained release of NVP.展开更多
Background CD4^＋T cell counts have been used as the indicator of human immunodeficiency virus type 1 （HIV-1） disease progression and thereby to determine when to start highly active antiretroviral therapy （HAART）...Background CD4^＋T cell counts have been used as the indicator of human immunodeficiency virus type 1 （HIV-1） disease progression and thereby to determine when to start highly active antiretroviral therapy （HAART）. Whether and how the baseline CD4^＋T cell count affects the immunological and viral responses or adverse reactions to nevirapine （NVP）-containing HAART in Chinese HIV-1 infected adults remain to be characterized. Methods One hundred and ninety-eight HIV-seropositive antiretroviral therapy （ART）-naive subjects were enrolled into a prospective study from 2005 to 2007. Data were analyzed by groups based on baseline CD4^＋T cell counts either between 100-200 cells/μl or 201-350 cells/μl. Viral responses, immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 52, 68, 84, 100. Results Eighty-six and 112 subjects ranged their CD4^＋T cell counts 100-200 cells/μl and 201-350 cells/μl, respectively. The pre-HAART viral load in CD4 201-350 cells/μl group was significantly lower than that in CD4 100-200 cells/μl group （P=0.000）. After treatment, no significant differences were observed between these two groups either in the plasma viral load （pVL） or in the viral response rate calculated as the percentage of pVL less than 50 copies/ml or less than 400 copies/ml. The CD4^＋T cell counts were statistically higher in the 201-350 group during the entire follow-ups （P 〈0.01） though CD4^＋ T cell count increases were similar in these two groups. After 100-week treatment, the median of CD4^＋ T cell counts were increased to 331 cells/μl for CD4 100-200 cells/μl group and to 462 cells/μl for CD4 201-350 cells/μl group. Only a slightly higher incidence of nausea was observed in CD4 201-350 cells/μl group （P=0.05） among all adverse reactions, including rash and liver function abnormality. Conclusions The pVLs and viral response rates are unlikely to be associated with the baseline CD4^＋T cell counts. Initiating HAART in Chinese HIV-1 infected patients with higher baseline CD4^＋T cell counts could result in higher total CD4^＋T cell counts thereby achieve a better immune recovery. These results support current guidelines to start HAART at a threshold of 350 cells/μl.展开更多
Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse ...Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues^1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.~2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.展开更多
A rapid and sensitive LC-MS/MS method for the simultaneous quantitation of lamivudine,zidovudine and nevirapine in human plasma using abacavir as internal standard has been developed and validated.The analytes and IS ...A rapid and sensitive LC-MS/MS method for the simultaneous quantitation of lamivudine,zidovudine and nevirapine in human plasma using abacavir as internal standard has been developed and validated.The analytes and IS were extracted from plasma by solid phase extraction using Oasis HLB cartridges and separated on a Hypurity Advance C18 column using a mixture of acetonitrile:0.1% formic acid(76:24,v/v)at a flow rate of 0.8 mL/min.Detection involved an API-4000 LC MS/MS with electrospray ionization in the positive ion mode and multiple-reaction monitoring for analysis.The method was validated according to FDA guidelines and shown to provide intra-and inter-day precision and accuracy within acceptable limits in a run time of only 3.5 min.The method was sucessfully applied to a pharmacokinetic study involving a single oral administration of a combination tablet to human male volunteers.展开更多
Introduction: Early infant diagnosis (EID) confers substantial benefit to HIV infected and HIV uninfected infants and to programmes providing prevention of mother to child transmission (MTCT), but has been challenging...Introduction: Early infant diagnosis (EID) confers substantial benefit to HIV infected and HIV uninfected infants and to programmes providing prevention of mother to child transmission (MTCT), but has been challenging to implement in resource limited settings. Objectives: To find out the rate of perinatal transmission in infants born to HIV positive mothers, to study the effect of various predisposing factors on HIV transmission and to evaluate the utility of dried blood spot (DBS) specimen for EID of HIV. Methods: Infants born to HIV positive mothers were tested according to National AIDS Control Organization (NACO) guidelines. Infants of 6 weeks to 6 months of age (n = 84) were diagnosed by DBS PCR;DBS positive results were confirmed by whole blood PCR. Infants 6 - 18 months (n = 47) were subjected to antibody test and if positive were confirmed by DNA PCR. Detailed history including type of delivery, single dose nevirapine (SDN) and breast feeding was taken. Results: The HIV transmission rate was 10.69%. In children ≤ 6 months, who did not receive SDN the positivity was 44.44% (4/9) whereas in those who received SDN it was 6.66% (5/75), (P = 0.0063). In children > 6 months the positivity rate was significantly higher in breast fed 42.85% (3/7) as compared to non breast fed 5% (2/40) children (P = 0.0187). There was 100% concordance between DBS and whole blood PCR. Conclusions: In resource limited settings, though HAART should be considered to further reduce MTCT during pregnancy and to prevent the emergence of resistance, SDN should be kept as an option for mothers coming directly in labour. Also, extended ART should be provided to mothers who want to breast feed their children. Early infant diagnosis using DBS specimens will further reduce the morbidity and mortality in these children.展开更多
Background: Multiple biochemical parameters related to cytolysis, cholestasis and/or liver failure, can be used to evaluate liver tolerance to antiretroviral (ARV) drugs. what parameters are most suitable for monitori...Background: Multiple biochemical parameters related to cytolysis, cholestasis and/or liver failure, can be used to evaluate liver tolerance to antiretroviral (ARV) drugs. what parameters are most suitable for monitoring early hepatic tolerance in the developing countries? Objective: to evaluate liver tolerance to NVP (nevirapine) or EFV (efavirenz)- based regimens during the first six months. Method: This is a preliminary prospective cohort study with 125 naive ivorian HIV1-infected patients, by observing the level of ALT (alanine aminotransferase), AST (aspartate aminotrans- ferase), ALP (alkaline phosphatase), GGT (gamma-glutamyl transferase), and TBR (total bilirubin). Results: variable changes are noticed in the level of various biochemical parameters from M0 to M6. Nevertheless, we found that the values of these parameters studied fall within normal ranges except for GGT which showed an increased level with NVP-based regimen. Biological liver tolerance to NVP or EFV-based regimen was good at M3 and M6 during therapy. The percentage of patients who had elevated ALT activity had tripled with each ARV regimen from M3 to M6. We noticed a decrease in the median value of transaminases (ALT and AST) from M0 to M6. This decrease was statistically significant for patients on EFV-based regimen from M0 to M3 and from M0 to M6. The ALP enzymes were the least affected after initiation of therapy, regardless of the regimen taken. In general,we noticed an hepatotoxicity of grade 1 or 2, in the two ARV regimens. The hepatotoxicity of grade 3 or 4 were rare (only with transaminases and GGT). Conclusion: we suggest a study of longer duration involving more patients, probably limited to the monitoring of transaminases (ALT and AST) and GGT, due to the results more or less sensitive about them in our analysis.展开更多
An old woman, 28 years old, weighing 74 kg was referred for skin detachment associated with bubbles and mucosal erosions. This clinical picture had occurred 15 days after the institution of a triple combination: AZT (...An old woman, 28 years old, weighing 74 kg was referred for skin detachment associated with bubbles and mucosal erosions. This clinical picture had occurred 15 days after the institution of a triple combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 20-week gestation. The woman was in her third gestation. The second case is aged 26, weighing 65 kg. This clinical picture had occurred 20 days after the administration of a triple therapy combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 32-week gestation. It was the fourth gestation. The birth of a stillborn had occurred the day before his admission into our service. The diagnosis of Toxic Epidermal Necrolysis with nevirapine was selected on the basis of the clinical and anamnestic arguments. The biological tests showed the following results: transaminases (ALT and AST) were within normal limits, blood glucose, and urea > 10 mmol/l. The evolution was marked by the patient death to Day 9 (D9) and at D2 of hospitalization. Discussion: NET and the SJS have been reported in pregnant women as potentially dangerous complications that are often associated with suspected drugs. Among these drugs, antiretroviral drugs, prescribed to pregnant women to prevent mother to child transmission of HIV are often reported. Our case is an illustration of the problem of HIV management in pregnant women. It also focuses on the association between pregnancy and Toxic Epidermal Necrolysis. Nevirapine is an effective drug in the regimens proposed in the management of HIV patients in limited resources countries. But the high frequency of toxidermia with this drug should lead to its replacement by other antiretrovirals least providers of toxidermia as anti proteases in the context of PMTCT programs.展开更多
Elevated alanine aminotransferase (ALT) levels in Human Immunodeficiency Virus (HIV) infected people is a major concern in the world and especially in Africa. It may lead to liver failure and even death. Certain antir...Elevated alanine aminotransferase (ALT) levels in Human Immunodeficiency Virus (HIV) infected people is a major concern in the world and especially in Africa. It may lead to liver failure and even death. Certain antiretroviral (ARV) drugs, such as nevirapine and efavirenz, are known to cause toxicity. Other causes of elevated ALT are viral hepatitis, the HIV virus itself and other drugs such as anti-tuberculosis drugs and alcoholism. The study aimed at determining the prevalence of elevated ALT levels in HIV positive patients on antiretroviral therapy during the period 2013 to 2014. This was a retrospective study which included 267 patient records from Katutura and Windhoek Central hospitals in Windhoek, Namibia. The subjects’ ages ranged from 21 to 82 years. The patients enrolled were on the first line treatment and their ALT levels were recorded at each monitoring period. ALT levels, viral hepatitis results and the antiretroviral therapy (ART) regimen were the most important aspects included in the study. Out of 267 patients, 18% had ALT elevation associated with grade 1 to 4 toxicity levels. The study found that 1.4% of patients developed severe liver toxicity (grade 3 and 4 toxicity). Toxicity occurred throughout the treatment period but was the highest at six months of treatment. Patients on nevirapine based regimens had lower toxicity compared to those receiving efavirenz based regimens. Patients who had HIV and viral hepatitis co-infection had high toxicity although the study found no severe hepatotoxicity in these patients.展开更多
基金supported by The National Research Council of Thailand (NRCT)Office of the Higher Education Commission and Chiang Mai University under the National Research Universities Initiative
文摘Objective: To generate insights into the mechanism of NVP induced hepatotoxicity. Methods: Liver(HepG2) cells were cultured with various concentrations of NVP. This cell line was chosen because it has low expression of cytochrome P450, allowing evaluation of the effects of NVP rather than specific metabolites. Cytotoxicity was determined using a proliferation assay and cell numbers were monitored using trypan blue exclusion assay for long term culture experiments and apoptosis induction was determined by morphological and biochemical investigation. Results: HepG2 cells treated with the highest concentration of NVP tested(819 μM) initially showed a rounded morphology and all cells had died by week three of exposure. Nuclear condensation and fragmentation, increased Annexin V/propidium iodide staining and caspase 9 activation all supported the induction of apoptosis in HepG2 cells in response to NVP treatment. Conclusions: There is a clear induction of apoptosis in response to NVP which suggests that NVP has significant cytotoxicity, over and above any cytotoxicity of metabolites and may contribute directly to patient hepatotoxicity.
文摘Background: There are two approved non-nucleoside reverse transcriptase inhibitor antiretroviral drugs;namely Nevirapine (NVP) and Efavirenz (EFV). Nevirapine and EFV have comparable clinical efficacy when administered in combination regimens. But there is a lack of recent evidence showing the effect of NVP and EFV-based ARTs on immunological responses in HIV infected individuals in Ethiopia in general and Addis Ababa in particular. Methods: Retrospective cohort study design was used to compare immunological response rate of NVP and EFV based HAART regimen in Addis Ababa. Four hundred ninety two HIV infected patients who started HAART in ten selected health facilities were included in the study. Rate of immunologic response was examined at the 6th, 12th, 18th, and 24th months of follow-up period. The time required to get immunological response was analyzed by Kaplan-Meier survival curve. Adjusted hazard ratio was calculated with a 95% confidence interval by Cox proportional hazards model to determine the rate of immunological response. To ascertain the association, bivariate and multi variable Cox proportional hazard model was used. Statistical significance was considered with two sides P-value of 0.05. Results: The mean CD4 count ranged between 132.2 cell/μl at baseline and 302.3 cell/μl at the end of the follow-up period. This change was significant at 95% of CI but did not show significant differences among the comparison group. The median time to get immunological response was 18 (75% percental 12) months. At the end of the follow-up period, 73.2% (76.6% for NVP and 69.8% for EVF P-value 0.13) of the study population had immunological response. Conclusion: As a conclusion, there was a robust and sustained CD4 response and the effect of NVP and EFV based ART on change of mean CD4 count and immunological response was comparable and effective. Initiation of ART with high baseline CD4 count, in combination of IPT and with either NVP or EFV based NNTI was recommended.
文摘Background: Over 90% of infection in children is acquired through mother to child transmission (MTCT). Nevirapine’s efficacy, safety and affordable cost make it the most preferred non-nucleoside reverse transcriptase inhibitor (NNRTI) for paediatric prophylactic use in resource limited settings. There are very few studies on pediatric adherence to antiretroviral prophylaxis, especially in very young infants. The objective of the study was to evaluate the adherence to nevirapine for prevention of mother to child transmission (PMTCT) amongst infants of HIV positive mothers in the first 6 weeks of life. Methods: This was a questionnaire based prospective cross-sectional multicenter study initiated in July 2015 and concluded in December 2017. The study was carried out at the Aids Prevention in Nigeria (APIN/HIV) human immunodeficiency paediatric clinics of the Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos State, 68 Nigerian Army Reference Hospital Yaba (68NARHY) Lagos, Nigeria and the Holy Family Catholic Hospital, Festac Town, Amuwo Odofin, Lagos State. Nevirapine adherence, in infants of 0 - 6 weeks was measured by maternal verbal reports. Results: Eighty-one (81) infants receiving nevirapine within the age of 0 - 6 weeks completed the study. Majority of the infants started treatment at birth (32%) and after 4 weeks (31%). 54% of the 81 respondents do not miss or skip their doses while 46% of respondents skip doses. Majority of the respondents 18 (49%) missed their doses for 24 - 48 hours while 25% missed their doses because they were away from home and 23% ran out of pills. 85.2% took ≥95% of the prescribed medications (good or high adherence ), 8.2% took 80% - 95% of doses (moderate adherence) while 6.2% took 0.05). Conclusions: The adherence rates found in this study are comparable to other studies in developing countries. But these rates are still low for good clinical outcomes. Different levels of adherence were documented with the majority having good or high adherence. Not all of the infants started treatment at birth and Institutional delivery should be encouraged to improve early initiation of prophylaxis. The finding of patients with low adherence rates among the study population calls for intensification of counselling on adherence and should continue to be an integral part of prevention of mother to child transmission. Improved access to antiretroviral agents and improved care delivery systems are important.
文摘A Novel stability indicating RP-UPLC chromatographic method was developed for analysis of Nevirapine in pharmaceutical formulations. The developed RP-UPLC method is superior in technology to conventional RP-HPLC with respect to speed, resolution, solvent consumption and cost of analysis. Nevirapine was subjected to the stress conditions like acid, base, thermal, oxidative and photolytic degradation. Nevirapine was found to degrade significantly in acid and thermal degradation. In acid degradation relative retention time with 0.42 is found as unknown impurity. New impurity was identified, isolated using mass based auto purification system and characterized by <sup>1</sup>H NMR (<sup>1</sup>D and <sup>2</sup>D) and HRMS experiments. Isolated impurity was showing molecular weight of 244.10, molecular formula C<sub>12</sub>H<sub>12</sub>N<sub>4</sub>O<sub>2</sub> and its name as 2-(3-Amino-4-methylpyridin-2-ylamino)nicotinic acid. The calibration graph was linear and the method showed less deviation in accuracy results. The test solution was found to be stable for 20 days when stored in the refrigerator between 2°C to 8°C. The developed RP-UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines. The intra-day and inter-day variation was less than 1%. The method was reproducible and selective for the estimation of Nevirapine. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating method.
文摘Transdermal drug delivery not only has contributed immensely to medical practice, but has enjoyed enormous interest in the field of cosmetic and pharmaceutical industries. Nevirapine, a non‐nucleoside reverse transcriptase inhibitor (NNRTI) is used clinically for the treatment of HIV‐ 1 infection. The aim of the present study is to investigate the influence of cosolvents (glycerol, propylene glycol, ethanol, polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80, sodium lauryl sulfate, sodium cholate and cetrimide) on the dermal permeability coefficient of nevirapine by utilizing established and recognized mathematical model that employs partition coefficient as one of its molecular descriptors. The partition coefficient of nevirapine is determined in chloroform-water system at room temperature using the shake flask method. The results show that all the cosolvents used in this study decrease the partition coefficient of nevirapine. The same decrease in the partition coefficient of nevirapine is observed with all the surfactants investigated. The order of dermal enhancement potential of the vehicles studied based on the predicted permeability coefficient is glycerol > propylene glycol > ethanol > polyethylene glycol 400 for the cosolvents while tween 20 > tween 80 > sodium lauryl sulfate > sodium cholate > cetrimide for the surfactants. The maximum predicted flux through skin was obtained by multiplying the predicted permeability coefficient and the drug aqueous solubility. As the rate of penetration into the skin is quantitatively assessed by the use of permeability coefficient, the findings suggest that for dermal formulation of nevirapine, glycerol and tween 20 are the most preferred vehicles out of the vehicles investigated. Furthermore, the results of the correlation coefficients obtained by plotting permeability coefficient or maximum predicted flux, versus logarithm partition coefficient indicate that permeability coefficient can be a more reliable parameter to predict transdermal absorption of nevirapine than flux.
文摘The development of the spectrofluorimetric method can be considered a promising alternative that is relatively less expensive and sufficiently reliable. In the current literature, no method for the analysis of nevirapine by spectro-fluorimetric has been reported. The proposed method is based on the transformation of naturally non-fluorescent nevirapine into a fluorescent derivative after chemical synthesis. Maximum excitation and emission wavelengths are 290 nm and 357 nm respectively. The analytical performance of the method demonstrates linearity in the concentration range 1.5 × 10<sup>-2</sup> and 13.5 × 10<sup>-2</sup> μg/mL with a correlation coefficient (r) greater than 0.999. The detection (LOD) and quantification (LOQ) limits found are 1.97 × 10<sup>-3</sup> μg/mL and 5.48 × 10<sup>-3</sup> μg/mL respectively. Recovery is achieved with 99.9% and 100.3% trueness, intra-day precision with a coefficient of variation of repeatability (CVr) of 0.99% and inter-day precision with a coefficient of variation of precision (CVR) of 1.7%. The method has been successfully applied in the analysis of 10 batches of nevirapine tablets and suspensions.
文摘The Nevirapine (NVP)/Polycaprolactone (PCL)/Nanoparticles hybrids systems have been developed as a potential platform for drug delivery, by solvent cast, as thin films. NVP, an antiretroviral drug, was included within PCL matrix containing three types of nanoparticles: an organoclay layered silicate Viscogel S7®(3% w/w), hydrophilic silica oxide particles Aerosil®A20 (0.25% w/w) and titanium dioxide particles (0.25% w/w). These systems were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), low-field nuclear magnetic resonance (NMR), ultraviolet-visible spectroscopy (UV), in-vitro dissolution testing and drug release mechanism kinetics. The PCL crystallization was affected by NVP incorporation, modifying its semi-crystalline structure to a less ordered structure. When nanoparticles and NVP were added, the T<sub>1</sub>H values increased, for PCL, PCL/S7, PCL/ SiO<sub>2</sub> and PCL/TiO<sub>2</sub> hybrids, suggesting that its addition produced a new material, with less molecular mobility, due to the new intermolecular interactions formation. It can consider a structure formation among the PCL chains, nanoparticles and NVP, with strong forces in the PCL/SiO<sub>2</sub>/NVP system. The amount of NVP included was around 1.5 ± 0.03 mg/cm<sup>2</sup>. In the in-vitro dissolution test, the PCL/SiO<sub>2</sub>/NVP system released the smallest amount of drug and this result could be attributed to the strong intermolecular interaction between the drug and the PCL/SiO<sub>2</sub> system. Higuchi’s model was the mathematical model chosen to treat the release data, since this model presented the highest coefficient correlation (r) value. The drug release probably occur by diffusion through the matrix pores, thus, these materials are suitable for sustained release of NVP.
文摘Background CD4^＋T cell counts have been used as the indicator of human immunodeficiency virus type 1 （HIV-1） disease progression and thereby to determine when to start highly active antiretroviral therapy （HAART）. Whether and how the baseline CD4^＋T cell count affects the immunological and viral responses or adverse reactions to nevirapine （NVP）-containing HAART in Chinese HIV-1 infected adults remain to be characterized. Methods One hundred and ninety-eight HIV-seropositive antiretroviral therapy （ART）-naive subjects were enrolled into a prospective study from 2005 to 2007. Data were analyzed by groups based on baseline CD4^＋T cell counts either between 100-200 cells/μl or 201-350 cells/μl. Viral responses, immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 52, 68, 84, 100. Results Eighty-six and 112 subjects ranged their CD4^＋T cell counts 100-200 cells/μl and 201-350 cells/μl, respectively. The pre-HAART viral load in CD4 201-350 cells/μl group was significantly lower than that in CD4 100-200 cells/μl group （P=0.000）. After treatment, no significant differences were observed between these two groups either in the plasma viral load （pVL） or in the viral response rate calculated as the percentage of pVL less than 50 copies/ml or less than 400 copies/ml. The CD4^＋T cell counts were statistically higher in the 201-350 group during the entire follow-ups （P 〈0.01） though CD4^＋ T cell count increases were similar in these two groups. After 100-week treatment, the median of CD4^＋ T cell counts were increased to 331 cells/μl for CD4 100-200 cells/μl group and to 462 cells/μl for CD4 201-350 cells/μl group. Only a slightly higher incidence of nausea was observed in CD4 201-350 cells/μl group （P=0.05） among all adverse reactions, including rash and liver function abnormality. Conclusions The pVLs and viral response rates are unlikely to be associated with the baseline CD4^＋T cell counts. Initiating HAART in Chinese HIV-1 infected patients with higher baseline CD4^＋T cell counts could result in higher total CD4^＋T cell counts thereby achieve a better immune recovery. These results support current guidelines to start HAART at a threshold of 350 cells/μl.
文摘Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues^1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.~2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.
文摘A rapid and sensitive LC-MS/MS method for the simultaneous quantitation of lamivudine,zidovudine and nevirapine in human plasma using abacavir as internal standard has been developed and validated.The analytes and IS were extracted from plasma by solid phase extraction using Oasis HLB cartridges and separated on a Hypurity Advance C18 column using a mixture of acetonitrile:0.1% formic acid(76:24,v/v)at a flow rate of 0.8 mL/min.Detection involved an API-4000 LC MS/MS with electrospray ionization in the positive ion mode and multiple-reaction monitoring for analysis.The method was validated according to FDA guidelines and shown to provide intra-and inter-day precision and accuracy within acceptable limits in a run time of only 3.5 min.The method was sucessfully applied to a pharmacokinetic study involving a single oral administration of a combination tablet to human male volunteers.
文摘Introduction: Early infant diagnosis (EID) confers substantial benefit to HIV infected and HIV uninfected infants and to programmes providing prevention of mother to child transmission (MTCT), but has been challenging to implement in resource limited settings. Objectives: To find out the rate of perinatal transmission in infants born to HIV positive mothers, to study the effect of various predisposing factors on HIV transmission and to evaluate the utility of dried blood spot (DBS) specimen for EID of HIV. Methods: Infants born to HIV positive mothers were tested according to National AIDS Control Organization (NACO) guidelines. Infants of 6 weeks to 6 months of age (n = 84) were diagnosed by DBS PCR;DBS positive results were confirmed by whole blood PCR. Infants 6 - 18 months (n = 47) were subjected to antibody test and if positive were confirmed by DNA PCR. Detailed history including type of delivery, single dose nevirapine (SDN) and breast feeding was taken. Results: The HIV transmission rate was 10.69%. In children ≤ 6 months, who did not receive SDN the positivity was 44.44% (4/9) whereas in those who received SDN it was 6.66% (5/75), (P = 0.0063). In children > 6 months the positivity rate was significantly higher in breast fed 42.85% (3/7) as compared to non breast fed 5% (2/40) children (P = 0.0187). There was 100% concordance between DBS and whole blood PCR. Conclusions: In resource limited settings, though HAART should be considered to further reduce MTCT during pregnancy and to prevent the emergence of resistance, SDN should be kept as an option for mothers coming directly in labour. Also, extended ART should be provided to mothers who want to breast feed their children. Early infant diagnosis using DBS specimens will further reduce the morbidity and mortality in these children.
文摘Background: Multiple biochemical parameters related to cytolysis, cholestasis and/or liver failure, can be used to evaluate liver tolerance to antiretroviral (ARV) drugs. what parameters are most suitable for monitoring early hepatic tolerance in the developing countries? Objective: to evaluate liver tolerance to NVP (nevirapine) or EFV (efavirenz)- based regimens during the first six months. Method: This is a preliminary prospective cohort study with 125 naive ivorian HIV1-infected patients, by observing the level of ALT (alanine aminotransferase), AST (aspartate aminotrans- ferase), ALP (alkaline phosphatase), GGT (gamma-glutamyl transferase), and TBR (total bilirubin). Results: variable changes are noticed in the level of various biochemical parameters from M0 to M6. Nevertheless, we found that the values of these parameters studied fall within normal ranges except for GGT which showed an increased level with NVP-based regimen. Biological liver tolerance to NVP or EFV-based regimen was good at M3 and M6 during therapy. The percentage of patients who had elevated ALT activity had tripled with each ARV regimen from M3 to M6. We noticed a decrease in the median value of transaminases (ALT and AST) from M0 to M6. This decrease was statistically significant for patients on EFV-based regimen from M0 to M3 and from M0 to M6. The ALP enzymes were the least affected after initiation of therapy, regardless of the regimen taken. In general,we noticed an hepatotoxicity of grade 1 or 2, in the two ARV regimens. The hepatotoxicity of grade 3 or 4 were rare (only with transaminases and GGT). Conclusion: we suggest a study of longer duration involving more patients, probably limited to the monitoring of transaminases (ALT and AST) and GGT, due to the results more or less sensitive about them in our analysis.
文摘An old woman, 28 years old, weighing 74 kg was referred for skin detachment associated with bubbles and mucosal erosions. This clinical picture had occurred 15 days after the institution of a triple combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 20-week gestation. The woman was in her third gestation. The second case is aged 26, weighing 65 kg. This clinical picture had occurred 20 days after the administration of a triple therapy combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 32-week gestation. It was the fourth gestation. The birth of a stillborn had occurred the day before his admission into our service. The diagnosis of Toxic Epidermal Necrolysis with nevirapine was selected on the basis of the clinical and anamnestic arguments. The biological tests showed the following results: transaminases (ALT and AST) were within normal limits, blood glucose, and urea > 10 mmol/l. The evolution was marked by the patient death to Day 9 (D9) and at D2 of hospitalization. Discussion: NET and the SJS have been reported in pregnant women as potentially dangerous complications that are often associated with suspected drugs. Among these drugs, antiretroviral drugs, prescribed to pregnant women to prevent mother to child transmission of HIV are often reported. Our case is an illustration of the problem of HIV management in pregnant women. It also focuses on the association between pregnancy and Toxic Epidermal Necrolysis. Nevirapine is an effective drug in the regimens proposed in the management of HIV patients in limited resources countries. But the high frequency of toxidermia with this drug should lead to its replacement by other antiretrovirals least providers of toxidermia as anti proteases in the context of PMTCT programs.
文摘Elevated alanine aminotransferase (ALT) levels in Human Immunodeficiency Virus (HIV) infected people is a major concern in the world and especially in Africa. It may lead to liver failure and even death. Certain antiretroviral (ARV) drugs, such as nevirapine and efavirenz, are known to cause toxicity. Other causes of elevated ALT are viral hepatitis, the HIV virus itself and other drugs such as anti-tuberculosis drugs and alcoholism. The study aimed at determining the prevalence of elevated ALT levels in HIV positive patients on antiretroviral therapy during the period 2013 to 2014. This was a retrospective study which included 267 patient records from Katutura and Windhoek Central hospitals in Windhoek, Namibia. The subjects’ ages ranged from 21 to 82 years. The patients enrolled were on the first line treatment and their ALT levels were recorded at each monitoring period. ALT levels, viral hepatitis results and the antiretroviral therapy (ART) regimen were the most important aspects included in the study. Out of 267 patients, 18% had ALT elevation associated with grade 1 to 4 toxicity levels. The study found that 1.4% of patients developed severe liver toxicity (grade 3 and 4 toxicity). Toxicity occurred throughout the treatment period but was the highest at six months of treatment. Patients on nevirapine based regimens had lower toxicity compared to those receiving efavirenz based regimens. Patients who had HIV and viral hepatitis co-infection had high toxicity although the study found no severe hepatotoxicity in these patients.
