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@#Introduction: The HIV epidemic in Malaysia predominantly affects males (90% of total HIV cases) mostly intravenous drugs users. Nevirapine-based of highly active antiretroviral therapy (HAART) once- or twice-daily dosage improve accessibility and effectiveness of antiretroviral treatment for HIV positive intravenous drug users (IDUs) receiving methadone maintenance treatment. Studies reported that concomitant administration of nevirapine with methadone reduced methadone plasma concentration. Since methadone and nevirapine were both known to be the substrate for cytochrome 2B6 (CYP 2B6), concomitant use of both drugs may affect nevirapine concentration too. However, methadone effect on nevirapine concentration is still unclear. This is a cross sectional study which reports how methadone co-administration affects the pharmacokinetic parameters of nevirapine in people living with HIV (PLHIV). Methods: 112 patients receiving nevirapine-based antiretroviral drugs were recruited. Seventeen were maintained with methadone without withdrawal symptoms. High-performance liquid chromatography was used to measure plasma nevirapine concentrations. Nevirapine population pharmacokinetics was modelled with a non-parametric approach using Pmetrics software. Result: According to univariate analysis, concurrent methadone administration increased the clearance of nevirapine by 25.3% (p = 0.046). Multivariate analysis showed that methadone medication was independently linked with lower nevirapine concentrations and area-under-curve (Cmin was reduced by 15.2%, p = 0.011, Cmax 19.5%; p = 0.003, AUC12 16.2%; p = 0.021 respectively). Conclusion: This study provides in-vivo evidence of methadone co-administration reducing nevirapine exposure. Since a low concentration of nevirapine will lead to treatment failure, monitoring is essential for PLHIV using both medications at the same time.
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Background: Human immunodeficiency virus (HIV) infection is increasing at an alarming rate globally. Apart from heterosexual route, mother to-child transmission is the next most important route of HIV transmission accounting for over 90% of infections in children. The present retrospective study is undertaken to evaluate the effectiveness of implementation of PPTCT programmed in GMERS Medical College, Sola, Ahmedabad, Gujarat, India.Methods: At ICTCs, registered ANCs are counseled and tested for HIV. HIV+ve ANCs are linked to services and followed-up for institutional delivery. Antiretroviral prophylaxis with nevirapine was given to seropositive mother-baby pairs during delivery and children testing. HIV+ve ANCs since 2014 to 2016 subsequently delivered till December 2018 and their exposed children followed up till 18 months for confirmation of their seropositivity status in PPTCT were study at GMERS medical college, sola, Ahmedabad, Gujarat, India.Results: 13595 ANCs registered, 100% were counseled pre-test, and 99.5% of them tested, 79.5% were counseled post-test. CD4 testing was carried out in all HIV+ve ANCs. 55 ANCs were detected HIV+ve inclusive of 37 new registered, 16 re-pregnancy and 2 unregistered cases. 55 pregnancy outcomes reported institutionally total 85.9% delivered at institute out of them 26.5% were caesarian sections and 62.4% delivered vaginally. Out of 48 live births, 47 sdNVP-MB-Pair were given. 48 children were traced till 18 months, 82.5% of live births were alive, and 68.75% of live births were tested. 1 was found HIV+ve with history of adherence to all prescribed PPTCT guidelines.Conclusions: PMTCT services - counseling and testing should be provided to all ANCs. EDD-based tracking, institutional deliveries, postnatal counseling to be encouraged along with complete MB pair coverage, capacity building of concerned staff regarding delivery of HIV+ve ANCs and exposed children tracking.
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Background: : In Prevention of Parent to Child Transmission (PPTCT) program in India, single dose Nevirapine was used for prevention of intrapartum transmission of HIV, but the protective efficacy of this regimen in Indian population is not beyond question. Objective: To analyze the protective efficacy of single dose Nevirapine prophylaxis in preventing mother to child transmission of HIV and comparing the effect of Nevirapine prophylaxis in different types of infant feeding practices and modes of delivery. Methods: A retrospective cohort study was carried out through analysis of secondary data during October 2010 to September 2011 from 16 Integrated Counseling and Testing Centers (ICTCs) having DNAPCR (Polymerase Chain Reaction) collection facility in West Bengal among 224 babies born of HIV infected mothers, 168 unexposed (covered with intrapartum Nevirapine) and 56 exposed (not covered with intrapartum Nevirapine) to risk of transmission. HIV reactivity in babies was confirmed by DNA PCR of Dry Blood spot from 6 weeks age onwards. Data was entered and analyzed using Epi Info version 3.5.1 and Statistical Package for Social Sciences software version (SPSS 16.0). Results: About 10.12% of those received Nevirapine were found HIV reactive compared to 26.79% of those who did not. Overall Relative Risk of non coverage of Nevirapine for vertical transmission of HIV was 2.65 (95% CI : 1.42 – 4.95). Overall Attributable Risk was 62.22%. Conclusion: Since in 62.2% cases vertical transmission of HIV was prevented, additional regimen may be thought of for rest 37.8% cases.
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Testicular toxicity has been implicated in highly active anti-retroviral therapy (HAART) treatment. Hence there is need to identify an effective antioxidant product that can alleviate testicular necrosis due to HAART administration. Forty eight adult male Sprague-Dawley rats were used in this study. The animals were divided into eight (8) groups: A-H (n= 6). Group A animals received normal saline as the control; Group B was given Nevirapine (Nv); Group C was given Kolaviron (Kv); Group D was given vitamin C; Group E was given Nv and Kv; Group F was given Nv and Vitamin C; Group G was given Nv for 56 d and Kv for 28 d serving as a withdrawal group; Group H was given corn oil. Nv, Kv and Vit. C were given at 1.54, 200 and 250 (mg·kg)/bw respectively while all administrations were through oral gavage. The body weights were taken every other day. Thereafter, they were anaesthetized with halothane. The testes were excised, weighed, fixed in Bouin's fluid and stained with H&E while the epididymes removed for semen fluid analyses. The results showed a significant (P<0.05) decrease in sperm motility in group E (Nevirapine + kolaviron) when compared with group F (Nevirapine + Vitamin C) while Sperm count was not significantly different (P>0.05) across the groups. The testicular histoarchitectural studies revealed indistinct spermatogonia, necrotic interstititial endocrine cells in the altered interstitial space, fragmented spermatids, atrophy of mature spermatocytes, degenerated germ cells, obliterated seminiferous tubules lumen, undifferentiated spermatogonia and cellular debris in the somniferous tubules lumen of nevirapine administered group but normal across the other groups. In the testis, there were no significant reduction in SOD, Catalase and GPx activities but a significant decrease in GST activity (P<0.001) when group E was compared with group F. In conclusion, vitamin C presents a better remediation in nevirapine induced spermiotoxicity compared to kolaviron in Sprague-Dawley rats.
La toxicidad testicular ha sido implicada en la terapia antirretroviral altamente activa (TARAA). Por lo tanto existe la necesidad de identificar un producto antioxidante eficaz que pueda aliviar la necrosis testicular en la administración de la TARAA. Cuarenta y ocho ratas macho Sprague-Dawley adultas fueron utilizadas. Los animales se dividieron en ocho (8) grupos: AH (n= 6). Grupo A, animales recibieron solución salina normal como el control; Grupo B, recibió Nevirapina (Nv); Grupo C, recibió Kolaviron (Kv); Grupo D, recibió vitamina C; Grupo E, recibió Nv y Kv; Grupo F, recibió Nv y vitamina C; Grupo G, recibió Nv durante 56 d y Kv por 28 d como un grupo de retirada; Grupo H, recibió aceite de maíz. Nv, Kv y Vit. C se administraron en dosis de 1, 54, 200 y 250 (mg · kg) de peso corporal respectivamente; todas las administraciones fueron por sonda oral. Los pesos corporales se tomaron cada dos días. A partir de ese momento los animales fueron anestesiados con halotano. Los testículos fueron extirpados, pesados y fijados en solución de Bouin y teñidos con H&E, mientras que el epidídimo se retiró para analizar el semen. Los resultados mostraron un descenso (p<0,05) en la motilidad de los espermatozoides en el grupo E (Nevirapina + Kolaviron) en comparación con el grupo F (Nevirapina + vitamina C), mientras que el recuento espermático no mostró diferencias significativas (P>0,05) entre los grupos. El estudio de la histoarquitectura testicular reveló espermatogonias indiferenciadas, con células intersticiales necróticas en el espacio intersticial y espermátidas fragmentadas. Además, en el grupo que recibió Nevirapina mostró espermatocitos maduros atrofiados, degeneración de células germinales, lumen de los túbulos seminíferos obliterados, espermatogonias indiferenciadas y restos celulares en el lumen de los tubulos seminíferos. En el resto de los grupos los resultados fueron normales. En el testículo hubo una reducción significativa en las actividades de la superóxido dismutasa, catalasa y glutatión peroxidasa, pero una disminución significativa en la actividad glutatión S-transferasa (P <0,001) al comparar los grupo E y F.
Subject(s)
Animals , Male , Rats , Antioxidants/pharmacology , Garcinia kola/chemistry , Nevirapine/toxicity , Plant Extracts/pharmacology , Superoxide Dismutase/antagonists & inhibitors , Testis/drug effects , Anti-HIV Agents/toxicity , Ascorbic Acid/pharmacology , Biflavonoids/pharmacology , Body Weight , Catalase/antagonists & inhibitors , Glutathione Peroxidase/antagonists & inhibitors , Rats, Sprague-Dawley , Seeds , Sperm Count , Sperm Motility/drug effects , Testis/enzymology , Testis/pathologyABSTRACT
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.
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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.
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Objective To research the nevirapine-related substances method in the second supplement of Chinese Pharma- copoeia(Ch.P) 2010 edition, and explore the existing problems. Methods In-depth comparison of the nevirapine-related substances test method in Ch.P, United States Pharmacopoeia(USP) and European Pharmacopoeia(EP) ; three consecutive batches of nevirapine produced at a pharmaceutical factory were detected, and inspection situation of the related substances was compared. Results According to the Ch.P method we detected three impurities, while according to the other two pharmacopoeias we detected four impu¬rities. "Ch.P" leaves out the biggest single impurity. Conclusion We proved that the second supplement of Ch.P 2010 edition has the problem of residual impurities in the nevirapine-related substances test method, and propose to revise the nevirapine-related sub¬stances method.
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Objective:To prepare nevirapine nanosuspensions ( Nev-NS) and study the pharmacokinetics in rats. Methods:Nev-NS was prepared by a high pressure homogenization technology. The particle size, PDI and Zeta potential of the nanosuspensions were used as the indices to determine the influencing factors in the preparation process. Nevirapine plasma concentration was detected by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results: The particle size, PDI and Zeta potential of Nev-NS was (456. 1 ± 72. 1) nm, 0. 441 ± 0. 072 and ( -24. 4 ± 4. 7) mV, respectively. AUC0-12 of Nev and Nev-NS was (7. 57 ± 0.52) and (11.72 ±1.83) mg·h·L-1, t1/2 was (2.45 ±0.31) and (3.16 ±0.39) h, Tmax was (1.43 ±0.38) and (1.61 ± 0. 32) h and Cmax was (1. 62 ± 0. 42) and (3. 15 ± 0. 52) mg·L-1 , respectively. Conclusion:Nev-NS can improve the pharmacoki-netic behavior of Nev in rats significantly, and obviously enhance the bioavailability when compared with nevirapine suspensions.
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Objective To research the nevirapine-related substances method in the second supplement of Chinese Pharma-copoeia(Ch.P) 2010 edition, and explore the existing problems. Methods In-depth comparison of the nevirapine-related substances test method in Ch.P, United States Pharmacopoeia(USP) and European Pharmacopoeia(EP);three consecutive batches of nevirapine produced at a pharmaceutical factory were detected, and inspection situation of the related substances was compared. Results According to the Ch.P method we detected three impurities, while according to the other two pharmacopoeias we detected four impu-rities. Ch.P leaves out the biggest single impurity. Conclusion We proved that the second supplement of Ch.P 2010 edition has the problem of residual impurities in the nevirapine-related substances test method, and propose to revise the nevirapine-related sub-stances method.
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A rapid, economic and robust stability indicating HPLC method was developed and validated to quantify Tenofovir disoproxil Fumarate (TDF), Emtricitabine (EMT) and Nevirapine (NVP) simultaneously at single wavelength (254 nm) in order to assess the in vitro drug release profile from tablet formulations. Chromatographic separation was performed with a gradient elution of samples on a 4.6 mm x 150 mm, 5 μm, Inertsil ODS-2 column with buffered mobile phase containing solvent A (10 Mm ammonium acetate buffer, pH 4.6) and solvent B ( acetonitrile) at a flow rate of 1.0 mL/min). In dissolution studies, the sink condition was optimized based on quantitative solubility of TDF, EMT and NVP standards in different dissolution medium as recommended by USP. The proposed HPLC method and dissolution test condition were validated as per ICH guidelines. The results obtained meet the regulatory criteria thereby confirming that the method is suitable for routine quality control analysis and in vitro dissolution studies.
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Objective: Nevirapine (NVP) is a non nucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus disease. The present study was aimed to develop generic formulation of extended release (ER) tablets of Nevirapine anhydrous (NVP) using hydrophilic polymer. Method: Nevirapine NVP(ER) tablets were prepared by different manufacturing technology i.e. direct compression, roller compaction, and wet granulation method by employing hydrophilic polymer (HPMC K15M).The matrix granules were prepared by mixing drug along with polymer and diluents in different polymer ratio from wet granulation technology used water as a granulating fluid. Results: The prepared granules were evaluated for various physicochemical parameters by official procedure and compressed in tablets. The In-vitro release profile of various batches was prepared by different technologies and has been compared with the innovator product. In-vitro release profiles of NVP from ER tablets were determined using USP apparatus type II (Paddle), 50 rpm and bath temperature 37ºC. Dissolution of tablets was carried out in 900 ml of media (phosphate buffer pH 6.8). Samples were withdrawn at predetermined time intervals up to 24 hrs and analyzed using UV detector at a wavelength of 247 nm. Conclusion: Stress stability studies indicated that the formulation is stable and In-vitro release profile study showed that formulation using wet granulation technology.
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Aims: To assess seroprevalence of HIV among antenatal women and the extent of utilization of interventions to minimize the risk of mother-to-child transmission. Study Design: Descriptive cross-sectional study was carried out among antenatal women who attended integrated counseling and testing center (ICTC) of HIV. Sample sizes were determined from the number of pregnant women that attended ICTC. Place and Duration of Study: Data and samples were collected from a tertiary care hospital, Odisha, India during January 2009 to December 2012. Methodology: All pregnant women were counseled and tested for HIV by rapid test. All HIV-seropositive antenatal women (ANW) were linked to services and followedup for institutional delivery, single-dose nevirapine (sdNVP) prophylaxis, infant feeding options and testing of children at 18 months. Results: Out of 11,508 ANW registered and pretest counseled, 11,390 (98.97%) accepted HIV testing. Sixty women were found to be seropositive, thus showed seroprevalence rate of 0.53% (60/11,390). CD4 testing was carried out in all ANW and five (8.33%) were eligible for antiretroviral therapy (ART). Seven (11.67%) had opted for medical termination of pregnancy (MTP). All 48 ANW delivered institutionally, only 7 (14.58%) received cesarean delivery. Out of 46 live births, 5 (10.87%) ANW were on ART, 35/41 (85.37%) received sdNVP mother baby-pair prophylaxis and only 8/46 (17.39%) mother opted for replacement feeding. Twenty one children have reached 18 months till date and among them three (14.29%) were HIV-seropositive. All three were delivered vaginally, received sdNVP prophylaxis and were exclusively breast fed for 6 months. Conclusion: The HIV-seroprevalence rate among antenatal women was 0.53% and mother-to-child transmission (MTCT) rate was 14.29%. Reduction in MTCT rate needs pre or early antenatal HIV testing, prenatal antiretroviral medication, preference for cesarean delivery, 100% antiretroviral prophylaxis coverage and education on avoidance of breast feeding.
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A 42 year old man, a known case of AIDS receiving antiretroviral therapy – stavudine, lamivudine, and nevirapine since 4 weeks, was admitted with erythematous rash, with blisters, and abnormal liver function test. A diagnosis of Steven-Johnson syndrome was made excluding other opportunistic infection and differential diagnosis. Nevirapine was discontinued until the patient recovered. After recovery patient was started with stavudine, lamivudine, and efavirenz treatment without re-challenge with nevirapine.
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Stevens-Johnson syndrome (SJS) is a severe mucocutaneous skin reaction with extensive necrosis and detachment of the epidermis. Nevirapine is one of the high risk agents implicated in development of SJS. Here, we present a case of 27 years old male with HIV infection who was diagnosed to have SJS following administration of nevirapine.
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OBJECTIVE: To develop a method for determination of the contents and related substances in nevirapine zidovudine and lamivudine tablets. METHODS: The samples were separated on a Welch Ultimate AQ-C18 (4.6 mm × 250 mm, 5 μm) column by gradient elution using acetonitrile-methanol-0.025 mol·L-1 ammonium acetate solution (pH 4.0) as the mobile phase at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 277 nm, and the column temperature was 30°C. RESULTS: Nevirapine, lamivudine, and zidovudine had good liner relationship in the range of 10.3 - 310.9, 7.9 - 237.1, and 14.9 - 449.6 μg·mL-1, respectively. The correlation coefficients were all more than 0.9998. The average recoveries were 100.6% (RSD 0.4%), 100.0%(RSD 0.7%), and 100.2% (RSD 0.6%), respectively. Complete separation was achieved for the related substances (lamivudine acid, lamivudine related compound B, uracil, cytosine, thymine, nevirapine related compound A, and nevirapine related compound B). Cytosine, uracil, and thymine had good liner relationship in the range of 76.8 - 1152, 76.8 - 1152, and 744-14880 ng·mL-1, respectively. The correlation coefficients were all more than 0.9991. The average recoveries were 101.5% (RSD 4.8%), 102.8% (RSD 4.2%), and 101.2% (RSD 1.2%), respectively. CONCLUSION: The method is rapid, simple, and accurate with good reproducibility. It can be used for the quality control of nevirapine zidovudine and lamivudine tablets.
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Background: Over the years, single dose Nevirapine has been the cornerstone of the PPTCT program in India. However after successful scale up of ART program, initiation of ART for the pregnant was also considered another means of reducing the risk of transmission of HIV. As there were no specific studies to demonstrate the advantages of full-course ART during pregnancy compared to single dose Nevirapine, the current study was undertaken. Objectives: To study the socio-demographic variables, effectiveness of the different interventions and factors affecting the interventions among the PPTCT program beneficiaries. Materials and Methods: As part of the retrospective cohort study the details of the HIV positive pregnant women registered at four ICTCs of Andhra Pradesh were analyzed in two groups (Nevirapine and ART). Results: Total 145 pregnant women were studied and among them, 3.4% opted for MTP, 66.2% had live-birth and 60% had normal vaginal delivery. Upon testing for HIV at 18 months, 35% babies were HIV reactive in the Nevirapine group, 17.6% babies were HIV reactive in the ART group. Interpretation & Conclusion: The findings from the present study showed higher protection among babies with mothers on ART before delivery, compared to those with single dose Nevirapine.
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O presente trabalho se constitui de dois estudos clínicos realizados em Maputo, Moçambique, dos quais participaram 570 pacientes com infecção pelo HIV e tuberculose. Seus objetivos principais foram: a) determinar os parâmetros farmacocinéticos da rifampicina e da isoniazida na ausência e na presença da terapia antirretroviral (TARV) e b) comparar as concentrações plasmáticas da nevirapina e do efavirenz em vigência do tratamento para a tuberculose e após a sua descontinuação. Os dois estudos foram parte do ensaio clínicoANRS12146-CARINEMO, cujo objetivo foi comparar a eficácia e tolerância da terapia antirretroviral com base em nevirapina ou efavirenz quando coadministrada com a terapia padrão antituberculose. O tratamento para tuberculose foi composto por doses diárias de rifampicina e isoniazida, durante 6 meses, associadas a pirazinamida e etambutol nos dois primeiros meses. A TARV foi iniciada entre 4 e 6 semanas do tratamento para a tuberculose e os pacientes foram randomizados para receber nevirapina sem dose escalonada (200 mg duas vezes ao dia) ou efavirenz (600 mg dose única diária), ambos combinados com lamivudina e estavudina...
This work is composed of two clinical studies in Maputo, Mozambique, from which participated in 570 patients with co-infection with HIV and tuberculosis. Its main objectives were: a) determine the pharmacokinetic parameters of rifampicin and isoniazid in the absence and presence of antiretroviral therapy (ART) and b) compare the plasma concentrations of nevirapine and efavirenz in effectiveness of treatment for tuberculosis and after their discontinuation . The two studies were of the clínicoANRS12146-CARINEMO trial whose aim was to compare the efficacy and tolerability of antiretroviral therapy based on nevirapine or efavirenz when co-administered with the standard antituberculous therapy. The treatment for tuberculosis was composed of daily doses of rifampicin and isoniazid for 6 months, pyrazinamide and ethambutol associated with the first two months. The ART was initiated between 4 and 6 weeks of treatment for tuberculosis and patients were randomized to receive nevirapine without scaled dose (200 mg twice daily) or efavirenz (600 mg once daily), both in combination with lamivudine and stavudine...
Subject(s)
Humans , AIDS-Related Opportunistic Infections , HIV , Nevirapine , Rifampin , Tuberculosis , Antiretroviral Therapy, Highly Active , Drug Interactions , Hepatitis B virusABSTRACT
Background & objectives: Prevention of parent-to-child transmission (PPTCT) services are an integral part of National AIDS Control Programme and their critical appraisal is necessary for improving quality care. The present study was conducted to evaluate the performance of PPTCT services in West Bengal during April, 2008 - March 2009 and April 2009 - March 2010 and identify gaps in service delivery for making suitable recommendations. Methods: Data were collected from the Computerized Management Information System and validated by cross-checking records at each district. Focus group discussions (FGDs) were conducted among programme managers, counsellors and antenatal women attending the Integrated Counselling and Testing Centres. Performance indicators and outcomes of FGDs were analyzed. Results: The proportion of antenatal women tested declined in 2009-2010 from 2008-2009 (64.3 to 63.8%). Proportions of counseled cases also declined (72.5 vs. 68.4%). HIV positivity rates among those tested were 0.13 and 0.14 per cent, respectively in two years. Proportion of mother-baby pairs receiving nevirapine prophylaxis was increased by 5 per cent. Medical colleges, and category A districts having high HIV prevalence provided better services. Follow up services of HIV-exposed birth cohorts were grossly unsatisfactory. Interpretation & conclusions: Gaps were identified at each step of service delivery for which capacity building, improvement of infrastructure including laboratory services and ensuring emergency labour room testing up to the sub-district level were imperative. Outsourcing follow up services to other community based organizations may also be considered.
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Objective: To determine factors affecting serum levels of Efavirenz and Nevirapine and analyze the effect of Rifampicin on Nevirapine drug levels. Methods: A cross-sectional study was conducted on 30 HIV infected children on Antiretroviral therapy (ART) with Nevirapine or Efavirenz. Patients on simultaneous Rifampicin and Nevirapine were given higher doses of Nevirapine with regular monitoring of liver function tests. Trough levels (before morning dose of Nevirapine) and levels after 2 hours of administration of Nevirapine and levels of Efavirenz were assessed using HPLC and were checked to see if they fall within the therapeutic range. Results: Thirty patients (14 males) were enrolled in the study with 20 on Nevirapine and 10 (33.3%) on Efavirenz. Seven (23.3%) patients were simultaneously taking rifampicin. The mean Nevirapine dose given to the patients was 350.9±59.8mg/m2/day (on simultaneous rifampicin) and 309.2±54.6mg/m2/day (not on concurrent rifampicin). Thirteen (81.3%) of the 16 patients with trough Nevirapine had values in the normal range, 1 (6.3%) had low Nevirapine trough levels and 2 (12.5%) had high Nevirapine trough levels. Of the post 2 hours Nevirapine levels, 1 (5%) had low levels and 3 (15%) had high Nevirapine blood levels. Factors like age (P=0.4, P=0.4087), nourishment (P=0.2679, P=0.4132), ART combination (P=0.4199, P=0.4132), form of the drug (tablet/syrup) (P=0.1964, P=0.4696) or if it was being given as single or in a fixed dose combination (P=0.4179, P=0.4696) and even concurrent rifampicin administration (P=0.284, P=0.472) did not significantly affect the trough and post 2 hours Nevirapine values, respectively. All the five patients being given concurrent rifampicin had normal trough and post 2 hours levels of Nevirapine. The Efavirenz drug levels were 1.9±1.1 g/mL. Of the 10 patients on Efavirenz, 2 (20%) had high and 1 (10%) had low blood levels. Conclusion: Concurrent Rifampicin administration does not alter blood levels of Nevirapine; provided the dose of Nevirapine is increased by 20-30%. Formulation of drugs does not alter the blood levels provided drug administered is in the recommended dose.
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Data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of HIV-infected pregnant women and their newborns are limited in Argentina. We underwent a retrospective analysis of registries of HIV-infected pregnant women assisted at Helios Salud, Buenos Aires, Argentina (1997-2006). Variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. A total of 204 mother-child binomium were included. Maternal age (median): 29 years; 32.5% without prior diagnosis of HIV-infection. Baseline median CD4 T-cell count: 417 cell/μl; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55%) or a protease inhibitor (32%)]. Overall incidence of toxicity was 12.5%: rash (8%), anemia (3.5%) and hepatotoxicity (1%). Rash was associated with exposure to nevirapine. Eighty one percent and 50% reached HIV-viral loads <1000 and <50 copies/ml at the end of pregnancy, respectively. Twenty six percent had obstetric complications and 16% had preterm delivery. Of the newborns, 1.6% had congenital defects and 9% had neonatal complications. Overall neonatal mortality was 1% and perinatal transmission was 0.7%. Protease inhibitor use and obstetric complications were associated to preterm delivery while obstetric complications were associated with neonatal complications. In our population, hepatotoxicity was low despite frequent use of nevirapine. Protease inhibitor use was associated to preterm delivery. A favorable virological response and a low rate of perinatal transmission was observed, what supports the consensus that antiretroviral therapy benefits during pregnancy outweigh risks of maternal and neonatal adverse events.
La información sobre aspectos epidemiológicos, seguridad de drogas antirretrovirales y evolución de mujeres embarazadas HIV positivas y sus hijos es limitada en la Argentina. Realizamos un análisis retrospectivo de registros de embarazadas HIV positivas asistidas en Helios Salud, Buenos Aires, Argentina (1997-2006). Las variables asociadas con parto prematuro y complicaciones neonatales se estudiaron mediante análisis univariado y regresión logística. Estudiamos 204 binomios madre-hijo. Edad materna (mediana): 29 años, 32.5% sin diagnóstico previo de HIV. Recuento de linfocitos T CD4+ (mediana): 417 células/μl. El 98% recibió tratamiento antirretroviral durante el embarazo [dos análogos de nucleósidos más nevirapina (55%) o un inhibidor de proteasa (32%)]. La incidencia global de toxicidad fue 12.5%: erupción cutánea (8%), anemia (3.5%) y hepatotoxicidad (1%). La exposición a nevirapina se asoció con rash. El 81% y 50% alcanzaron cargas virales <1000 y <50 copias/ml preparto, respectivamente. Cesárea programada: 68%; complicaciones obstétricas: 26%; parto prematuro: 16%. De los neonatos, 1.6% presentaron defectos congénitos y el 9% complicaciones neonatales. La mortalidad neonatal fue 1% y la transmisión vertical: 0.7%. Las complicaciones obstétricas y el uso de inhibidores de proteasa se asociaron a parto prematuro; las complicaciones obstétricas se asociaron con complicaciones neonatales. La tasa de hepatotoxicidad fue baja a pesar de la utilización frecuente de nevirapina; el uso de inhibidores de proteasa se asoció a parto prematuro. Se observó una respuesta virológica favorable y una baja tasa de transmisión vertical, lo que apoya el consenso de que el beneficio de las drogas antirretrovirales durante el embarazo supera el riesgo de efectos adversos maternos y neonatales.