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At least 19 recordsLinked to original sources
PubMed2003

Predose infant nevirapine concentration with the two-dose intrapartum neonatal nevirapine regimen: association with timing of maternal intrapartum nevirapine dose.

OBJECTIVE: To evaluate cord blood and predose nevirapine concentrations in infants exposed to the two-dose intrapartum neonatal nevirapine regimen. METHODS: The authors obtained plasma samples for nevirapine assay from cord blood and just prior to the 48-hours to 72-hours after birth neonatal nevirapine dose from a subset of infants participating in PACTG 316, a randomized, placebo-controlled trial of the two-dose intrapartum neonatal nevirapine regimen added to standard antiretroviral therapy. RESULTS: Nevirapine concentrations were measured in 109 cord blood samples and 149 predose samples. Cord blood nevirapine concentrations were below the target concentration of 100 ng/mL (10-times the in vitro IC(50) of nevirapine against wild-type HIV) in eight (7%) of 109 infants (95% confidence interval [CI], 3%-14%); the concentrations in six of these infants were below the assay limit of quantitation. Predose infant nevirapine concentrations were below 100 ng/mL in 23 (15%) of 149 infants (95% CI, 10%-22%); the concentrations in 13 of these infants were below the assay limit of quantitation. Lower predose nevirapine concentrations were associated with lower cord blood concentrations and a shorter interval between maternal dosing and delivery. All but one of the infants with predose nevirapine concentrations below the assay limit of quantitation were born less than 2 hours after maternal dosing. CONCLUSION: Infants born less than 2 hours after maternal nevirapine dosing during labor should receive a dose of nevirapine immediately after birth in addition to the standard infant dose at 48 to 72 hours.

Adult↗
PubMed2005

Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine: implications for intervention studies.

BACKGROUND: Single-dose nevirapine is a highly cost-effective strategy to reduce perinatal HIV-1 transmission. Its major disadvantage is the selection of nevirapine resistance in 20% to 30% of women, probably attributable to the long elimination half-life of nevirapine. To develop intervention strategies, it is important to know the interpatient variability in nevirapine half-life in women receiving a single dose of nevirapine. METHODS: HIV-negative, healthy, nonpregnant Dutch women were eligible for this study. After administration of a single 200-mg dose of nevirapine to the subjects, blood was sampled for measurement of nevirapine twice a week for a total of 21 days. Nevirapine plasma levels were determined by a validated high-performance liquid chromatography method with a lower limit of quantification of 0.15 mg/L. The primary end point was the first sample with an undetectable nevirapine concentration. RESULTS: Forty-four subjects participated. The median age, height, and body weight (interquartile range) were 26 (21-33) years, 1.72 (1.68-1.75) m, and 64 (59-75) kg, respectively. The median elimination half-life of nevirapine was 56.7 hours, with a range of 25.6 to 164 hours. The time to the first undetectable nevirapine plasma concentration was 10 days in 4 subjects, 14 days in 12 subjects, 17 days in 12 subjects, and 21 days in 9 subjects. In the remaining 7 subjects, nevirapine was still detectable on day 21, the last day of sampling. Time to an undetectable nevirapine plasma concentration was influenced by oral contraceptive use but not by age, height, body weight, body surface area, alcohol use, or smoking. CONCLUSIONS: Most women who received a single 200-mg nevirapine dose still had detectable plasma concentrations of nevirapine after more than 2 weeks. This information is valuable for designing intervention studies to prevent the development of nevirapine resistance.

Adult↗
PubMed2004

Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy.

BACKGROUND: A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown. METHODS: We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and three and six months thereafter. RESULTS: After six months of therapy, the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log10 copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure. After six months of therapy, there was no significant difference between groups in the CD4 count (P=0.65). CONCLUSIONS: Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers.

Adult↗
PubMed1994

Alternating nevirapine and zidovudine treatment of human immunodeficiency virus type 1-infected persons does not prolong nevirapine activity.

The potential use of an alternating treatment strategy with nevirapine and zidovudine in prolonging the antiretroviral effects of nevirapine was evaluated. Ten human immunodeficiency virus type 1 (HIV-1)-infected p24 antigen-positive persons who had not received prior antiretroviral therapy were treated for 9-13 weeks with an alternating regimen of 1 week of nevirapine (200 mg/day) and 3 weeks of zidovudine (600 mg/day). Serum p24 antigen levels declined during the first week of nevirapine treatment (median, 59%); however, subsequent courses of nevirapine were characterized by rising p24 antigen levels, while antigen levels remained stable or declined during zidovudine treatment. Serum beta 2-microglobulin levels and CD4+ cell counts exhibited similar responses. HIV-1 isolates obtained from 2 patients revealed 40- and 1000-fold reductions in nevirapine sensitivity after 8 weeks. These findings demonstrate that alternating treatment with zidovudine and nevirapine does not prolong the effectiveness of nevirapine and does not prevent the development of nevirapine resistance.

Adolescent↗
PubMedDate not supplied

First-line nevirapine in combination with nucleoside analogues compared with nevirapine added to a salvage HAART.

BACKGROUND: Although non-nucleoside reverse transcriptase inhibitors are presently recommended as a part of an initial triple antiretroviral regimen, or as an adjunct to a rescue therapy in patients with poor response to highly active antiretroviral therapy (HAART), no controlled data are available comparing these two different strategies of administration of nevirapine. PATIENTS AND METHODS: Laboratorys data of 59 consecutive patients were prospectively followed up to compare the virologic and immunologic response to nevirapine in those starting a triple therapy combination (group A), versus subjects with prior HAART failure (group B). Laboratory data of 59 consecutive were prospectively followed up. RESULTS: In group A (33 cases), nevirapine was started with two nucleoside analogues in six subjects naïve to antiretrovirals, while in 27 cases it was added to a novel combination of nucleoside analogues. In group B (26 cases), highly experienced patients failing a protease inhibitor-containing HAART, were given nevirapine concurrently with nelfinavir in 19 cases, and with two protease inhibitors in seven patients. Compared with group B patients, subjects belonging to group A showed a more favorable 9-month virologic response (-2.2 Log10 after 9 months with two thirds of patients attaining viral suppression, versus -0.8 Log10 in group A, with only 34.6% of patients with undetectable viremia) (p < 0.001). A greater rise of mean absolute CD4+ lymphocyte count was also observed in group A as opposed to group B (p < 0.001). No significant difference was found comparing the laboratory response of antiretroviral-naïve versus -experienced patients, as well as of participants who changed one versus both nucleoside analogues at the time of nevirapine adjunct in group A, and between patients who switched to nelfinavir versus those treated with two protease inhibitors in group B. CONCLUSION: Nevirapine used as a component of an initial triple anti-HIV regimen seems to ensure a significantly more favorable virologic and immunologic outcome, compared with nevirapine adjunct to a salvage regimen carried out after HAART failure. Controlled data are needed, to better define the role of nevirapine in different therapeutic situations.

Adult↗
PubMed2000

Genotypic and phenotypic nevirapine resistance correlates with virological failure during salvage therapy including abacavir and nevirapine.

OBJECTIVE: To study the development of resistance during 8 weeks of salvage therapy with abacavir and nevirapine in combination with other reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). METHODS: Samples obtained at baseline and after 8 weeks of therapy from 16 heavily pretreated patients were analysed for genotypic and phenotypic resistance. Genotypic resistance was analysed in cell-associated DNA and plasma HIV-RNA using direct sequencing. Phenotypic resistance was analysed in a PBMC-based assay and in a recombinant virus assay. Plasma viral load was measured at baseline and after 2, 4 and 8 weeks of therapy. RESULTS: The majority of patients was genotypically and phenotypically resistant to lamivudine, abacavir, zidovudine and PIs, whereas 50% of the patients showed resistance to nevirapine at baseline in at least one of the methods used. After 8 weeks of salvage therapy, no additional development of resistance against nucleoside reverse transcriptase inhibitors and PIs could be detected. However, the amount of patients resistant to nevirapine increased to 83%. When the patients were divided into two groups according to baseline resistance against nevirapine, a significantly higher transient reduction in viral load was observed in patients with nevirapine-sensitive HIV at baseline compared to patients with resistant HIV at baseline. CONCLUSION: The transient effect of salvage therapy including abacavir and nevirapine was due to the effect of nevirapine. The lack of effect of abacavir was most likely due to cross-resistance between abacavir and lamivudine/zidovudine used in previous treatment.

Anti-HIV Agents↗
PubMed1996

A controlled trial of nevirapine plus zidovudine versus zidovudine alone in p24 antigenaemic HIV-infected patients. The Dutch-Italian-Australian Nevirapine Study Group.

OBJECTIVES: Nevirapine is a non-nucleoside reverse transcriptase inhibitor of HIV-1 which exhibits synergy in vitro with zidovudine (ZDV) and also is active against ZDV-resistant HIV. We evaluated the activity and safety of nevirapine in combination with ZDV in patients receiving long-term ZDV therapy. METHODS: We conducted a randomized, open-label, controlled 28-week study of nevirapine (200 mg daily for 2 weeks followed by 200 mg twice daily for 26 weeks) and continued ZDV (500-600 mg daily) versus continued ZDV alone in 49 HIV-1 p24 antigenaemic patients with CD4+ lymphocyte counts < 500 x 10(6)/l and who had been treated with ZDV for at least 6 months. RESULTS: Addition of nevirapine to ZDV resulted in a significant and rapid reduction in circulating RNA load (mean, 0.65), a mean CD4+ lymphocyte rise of 34 x 10(6)/l, a reduction in serum beta 2-microglobulin and a median fall in immune complex dissociated p24 antigen levels of 69%. These changes remained statistically significant for 4, 4, 12 and at least 28 weeks, respectively. The principal adverse event due to nevirapine was a hypersensitivity reaction comprising rash with or without fever and mucositis in eight (32%) patients, which was dose-limiting in seven patients. CONCLUSION: Nevirapine exhibits significant although transient anti-HIV activity in ZDV-pretreated patients but its use is frequently associated with a hypersensitivity reaction.

Adult↗
PubMed2006

Nevirapine levels after discontinuation of rifampicin therapy and 60-week efficacy of nevirapine-based antiretroviral therapy in HIV-infected patients with tuberculosis.

Seventy patients with human immunodeficiency virus (HIV) and tuberculosis coinfection who initiated nevirapine-based antiretroviral therapy and had trough nevirapine levels determined while receiving rifampicin were enrolled in a study. After discontinuation of rifampicin therapy, mean nevirapine levels (+/- standard deviation) increased from 5.4+/-3.5 mg/L to 6.4+/-3.4 mg/L (P=.047), but no nevirapine-related adverse events occurred. There was no statistically significant difference in 60-week antiviral efficacy between these patients and patients receiving nevirapine-based antiretroviral therapy alone (P>.05).

Adult↗
PubMed2005

Nevirapine plasma exposure affects both durability of viral suppression and selection of nevirapine primary resistance mutations in a clinical setting.

The relationship between nevirapine plasma concentrations and the durability of both viral suppression (VS) and selection of nevirapine primary resistance mutations (PRMs) was evaluated. A nevirapine trough concentration (Ctrough) of >4,300 ng/ml was found to predict longer VS. Patients with nevirapine Ctrough s ranging from 3,100 to 4,300 ng/ml had higher probabilities of developing PRMs than those with nevirapine Ctrough s below and above this concentration interval.

Adult↗
PubMed2006

A randomized, double-blind, placebo-controlled trial of combined nevirapine and zidovudine compared with nevirapine alone in the prevention of perinatal transmission of HIV in Zimbabwe.

BACKGROUND: A single dose of nevirapine (sdNVP) administered to both mother and infant can decrease mother-to-child transmission of human immunodeficiency virus (HIV) by 47%, compared with ultra-short course zidovudine therapy (usZDV). There is limited data about the benefit of usZDV added to sdNVP to prevent mother-to-child transmission. METHODS: We performed a double-blind, randomized, placebo-controlled trial to determine whether usZDV combined with sdNVP improved neonatal outcome, compared with sdNVP alone. Mothers were randomized to 1 of 2 treatment groups. Mothers in the usZDV/sdNVP group received a loading dose of zidovudine (600 mg administered orally) and continued to receive 300-mg doses of zidovudine orally every 3 h while in labor, and their infants received zidovudine at a dosage of 2 mg per kg of body weight 4 times per day orally for 72 h. Mothers and infants in the sdNVP group received zidovudine placebo dosed in the same manner. All mothers also received nevirapine at a dosage of 200 mg orally while in labor, and all infants received nevirapine 2 mg per kg of body weight orally within 72 h of delivery. RESULTS: The study was stopped on the basis of futility, because interim data showed that, at present trends, superiority would not be demonstrated. Results at 6 weeks of age were available for 609 infants. The primary end point of HIV RNA positivity or death occurred in 21.8% of infants in the usZDV/sdNVP arm and 23.6% of the infants in the sdNVP arm. CONCLUSION: usZDV, when added to a standard 2-dose regimen of sdNVP, did not demonstrate a clinically important decrease in the combined end point of mother-to-child transmission or infant death. High rates of adverse maternal and infant outcome in both study arms suggest that improved approaches are necessary.

Adult↗
PubMed2006

Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission.

Single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission of HIV-1 can select nevirapine (NVP)-resistant variants, but the frequency, duration, and clinical significance of this resistance is not well defined. We used a sensitive allele-specific PCR assay to assess the emergence and persistence of NVP-resistant variants in plasma samples from 22 women with HIV-1 subtype C infection who participated in a study of sdNVP for prevention of mother-to-child transmission of HIV-1. The women were categorized into three groups on the basis of detection of NVP resistance by standard genotype analysis. Group 1 (n = 6) had NVP resistance detected at 2 and 6 mo after sdNVP, but not at 12 mo. Group 2 (n = 9) had NVP resistance detected at 2 mo, but not 6 mo. Group 3 (n = 7) had no NVP resistance detected at any time point. Allele-specific PCR analysis for the two most common NVP resistance mutations (K103N and Y181C) detected NVP-resistant variants in most (16 of 21) samples that were negative for NVP resistance by standard genotype, at levels ranging from 0.1% to 20% 1 yr after treatment. The frequency of NVP-resistant mutations decreased over time, but persisted above predose levels for more than 1 yr in > or = 23% of the women. These findings highlight the urgent need for studies assessing the impact of sdNVP on the efficacy of subsequent antiretroviral therapy containing NVP or other nonnucleoside reverse transcriptase inhibitors.

Adult↗
PubMed2006

Plasma nevirapine levels and 24-week efficacy in HIV-infected patients receiving nevirapine-based highly active antiretroviral therapy with or without rifampicin.

Seventy human immunodeficiency virus (HIV)-infected patients receiving rifampicin and 70 HIV-infected patients not receiving rifampicin were enrolled to receive 400 mg of nevirapine-based highly active antiretroviral therapy per day. Mean plasma nevirapine levels at 8 and 12 weeks were lower in patients receiving rifampicin (P=.048). However, virological and immunological outcomes at 24 weeks were not different between the 2 groups (P>.05).

Adult↗
PubMed2006

Development of nevirapine resistance in infants is reduced by use of infant-only single-dose nevirapine plus zidovudine postexposure prophylaxis for the prevention of mother-to-child transmission of HIV-1.

We analyzed the development of nevirapine (NVP) resistance in human immunodeficiency virus type 1 (HIV-1)-infected Malawian infants who received regimens containing single-dose NVP (SD-NVP) for the prevention of mother-to-child transmission (MTCT) of HIV-1. All infants received SD-NVP, and some randomly received zidovudine (ZDV) as well. Mothers did or did not receive SD-NVP on the basis of when they arrived at the hospital for delivery. In infants 6-8 weeks of age, NVP resistance was less frequent when infants had received SD-NVP plus ZDV and mothers had not received SD-NVP than when infants had received SD-NVP alone and mothers had received SD-NVP (4/15 [27%] vs. 20/23 [87%]; P < .001). The risk of MTCT of HIV-1 was comparable with these regimens. Infant-only prophylaxis also eliminates the development of NVP resistance in mothers.

Anti-Retroviral Agents↗
PubMed2005

Genetic linkage of nevirapine resistance mutations in HIV type 1 seven days after single-dose nevirapine.

The HIVNET 012 trial in Uganda demonstrated that a regimen of single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. Previous studies show that HIV-1 with one or more NVP resistance (NVPR) mutations can be selected in many women as early as 7 days after single-dose NVP. We evaluated the genetic linkage of NVPR mutations in plasma from women in HIVNET 012 collected 7 days after single-dose NVP administration. The HIV-1 pol region was amplified and cloned from 20 plasma samples (16 with NVPR mutations detected by population sequencing and 4 with no NVPR mutations detected), and 10 clones from each sample were sequenced. Up to five different NVPR mutations were detected in clones from a single sample. K103N and Y181C were the most common mutations detected. Clones with two genetically linked mutations were detected in four samples. Different combinations of NVPR mutations were linked in individual clones, but none of the clones contained both K103N and Y181C. Further studies are needed to evaluate whether selection of minority variants with one or more NVPR mutations after single-dose NVP is clinically relevant.

Amino Acid Substitution↗
PubMed2004

Characterization of nevirapine resistance mutations in women with subtype A vs. D HIV-1 6-8 weeks after single-dose nevirapine (HIVNET 012).

OBJECTIVE: To compare the number and type of nevirapine (NVP) resistance mutations detected in Ugandan women with subtype A vs. D HIV-1 infection after single-dose NVP prophylaxis. DESIGN: In the HIVNET 012 trial, a higher rate of NVP resistance (NVPR) was seen in women with subtype D than A after single-dose NVP. In this study, the number and type of NVPR mutations detected 6-8 weeks after NVP were compared in women with subtypes A vs. D. METHODS: Plasma samples were available for 282 (92%) of 306 women who received NVP in HIVNET 012. Samples were analyzed with the ViroSeq HIV-1 Genotyping System (Applied Biosystems, Foster City, CA). Subtyping was performed by phylogenetic analysis of pol region sequences. RESULTS: Results were obtained for 279 women, including 147 with subtype A, 98 with subtype D, 6 with subtype C, and 28 with recombinant HIV-1. NVPR mutations were detected in 70 (25%) of 279 women. NVPR was more common in women with subtype D vs. A (35.7 vs. 19%, P = 0.0035). Complex patterns of NVPR mutations were detected in both subtypes. Among women with NVPR, 43% of women with subtype A and 46% of women with subtype D had >/=2 NVPR mutations. The mean number and pattern of NVPR mutations detected in women with subtypes A and D were similar. CONCLUSIONS: This study confirms a higher rate of NVPR in women with subtype D than A and further defines the pattern of NVPR mutations that emerge 6-8 weeks after single-dose NVP prophylaxis in these subtypes.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine.

OBJECTIVE: To evaluate the steady state pharmacokinetics of nevirapine (NVP) in HIV-infected children receiving a fixed-dose combination of stavudine, lamivudine and NVP. METHODS: This cross-sectional study enrolled 34 children (18 girls) who had received GPO-VIR S30 (30 mg stavudine, 150 mg lamivudine and 200 mg NVP) for at least 8 weeks. Tablets were divided into quarter fractions (1/4, 1/2, 3/4 or 1 tablet) to attain the NVP dosages of 120-200 mg/m every 12 h. Plasma NVP levels were measured at predose, and at 2 and 6 h after drug administration. RESULTS: The median age was 8.4 years (range, 3-15). Median CD4 lymphocyte count and percentage at study entry was 576 x 10 cells/l and 20.25%, respectively. The median pharmacokinetics parameters were area under the curve at 12 h, 78.4 h x mug/ml; minimum plasma drug concentration, 5.98 microg/ml; plasma half-life, 25.5 h; apparent oral clearance, 0.079 l/kg per h; and volume of distribution, 2.95 l/kg. Only one child had a minimum plasma drug concentration < 3.4 microg/ml (2.57 microg/ml). Of the 13 children who received GPO-VIR as their first-line regimen, 12 had plasma HIV-1 RNA < 400 copies/ml at 6-18 months, with a median CD4 lymphocyte increase of 216 and 433 x 10 cells/l at 6 and 12 months of treatment, respectively. CONCLUSIONS: The administration of GPO-VIR S30 fixed-dose combination tablets in fractions or as a whole tablet to children resulted in appropriate NVP exposure and satisfactory virological and immunological benefit. This finding confirms the effectiveness of using a fixed-dose combination as a "transitional option" while waiting for a paediatric fixed-dose combination drug formulation.

Adolescent↗
PubMed2005

Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1.

OBJECTIVE: To determine nevirapine (NVP) plasma levels during the postpartum period after a single intrapartum NVP dose for the prevention of mother-to-child transmission. METHODS: Plasma samples at delivery and during days 8 to 45 postpartum were obtained from HIV-infected Thai women who received an intrapartum NVP dose in the Perinatal HIV Prevention Clinical Trial-2 (PHPT-2) for the prevention of perinatal HIV transmission. These data were combined with NVP concentration data from 2 phase 1 studies of NVP for a population analysis. RESULTS: The median NVP level fell to 68 ng/mL (range: <50-228, n = 43) 8 to 14 days after dosing and to 51 ng/mL (range: <50-166, n = 25) between 15 and 21 days. During the second and third weeks postpartum, NVP levels were below the limit of quantitation in 23% and 44% of samples, respectively. Between 21 and 45 days, no sample had a quantifiable NVP concentration. A simulation derived from the population analysis predicts that NVP concentration falls to less than 10 ng/mL in 5% of women by 11 days, in 50% of women by 17.5 days, and in 95% of women by 28 days. CONCLUSIONS: Significant NVP concentrations remained for up to 20 days in these Thai women. To ensure that coverage is maintained until NVP concentrations fall to nonsuppressive levels, 1 month of additional antiretroviral treatment after delivery should be considered to prevent the emergence of resistant viruses.

Adolescent↗