ArticleHIV clinical trials
Pharmacokinetics and safety of nelfinavir when used in combination with zidovudine and lamivudine in HIV-infected pregnant women: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 353.
Article in HIV clinical trials. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00000887 (A Phase I Trial of the Safety, Tolerance, and Pharmacokinetics of Oral Nelfinavir), which is not on this map. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Trial of the Safety, Tolerance, and Pharmacokinetics of Oral Nelfinavir (Viracept) Co-Administered With Zidovudine (ZDV) and Lamivudine (3TC) in HIV Infected Pregnant Women and Their Infants
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.PLoS medicine · 2016Pooled it
- Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.Clinical pharmacokinetics · 2014Pooled it
- Pharmacokinetics of Increased Nelfinavir Plasma Concentrations in Women During Pregnancy and Postpartum.Journal of clinical pharmacology · 2019Trial
- Steady-state pharmacokinetics, cord blood concentrations, and safety of ritonavir-boosted fosamprenavir in pregnancy.Journal of acquired immune deficiency syndromes (1999) · 2013Trial
- Atazanavir pharmacokinetics with and without tenofovir during pregnancy.Journal of acquired immune deficiency syndromes (1999) · 2011Trial
- Postpartum viral load rebound in HIV-1-infected women treated with highly active antiretroviral therapy: AIDS Clinical Trials Group Protocol A5150.HIV clinical trialsTrial
- Application of physiologically based pharmacokinetic modeling for sertraline dosing recommendations in pregnancy.NPJ systems biology and applications · 2020Article
- Nanotechnology Based Repositioning of an Anti-Viral Drug for Non-Small Cell Lung Cancer (NSCLC).Pharmaceutical research · 2020Article
- Pharmacological induction of selective endoplasmic reticulum retention as a strategy for cancer therapy.Nature communications · 2020Article
- The integrated stress response promotes B7H6 expression.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Factors Associated with Lower Respiratory Tract Infections in HIV-Exposed Uninfected Infants.AIDS research and human retroviruses · 2018Article
- Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy.Journal of medical virology · 2016Observational
- The risk of viral rebound in the year after delivery in women remaining on antiretroviral therapy.AIDS (London, England) · 2015Observational
- Drug labeling and exposure in neonates.JAMA pediatrics · 2014Article
- Review
- Pharmacokinetic optimization of antiretroviral therapy in pregnancy.Clinical pharmacokinetics · 2012Review
- A PBPK Model to Predict Disposition of CYP3A-Metabolized Drugs in Pregnant Women: Verification and Discerning the Site of CYP3A Induction.CPT: pharmacometrics & systems pharmacology · 2012Article
- HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury.International journal of hepatology · 2012Article
- Nelfinavir and its active metabolite, hydroxy-t-butylamidenelfinavir (M8), are transferred in small quantities to breast milk and do not reach biologically significant concentrations in breast-feeding infants whose mothers are taking nelfinavir.Antimicrobial agents and chemotherapy · 2011Article
- Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.Journal of acquired immune deficiency syndromes (1999) · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundCombination antiretroviral regimens including nelfinavir (NFV) are commonly used in pregnancy. We studied the safety, antiviral effect, and pharmacokinetics of NFV and its M8 metabolite with two dosing regimens in combination with zidovudine (ZDV) and lamivudine (3TC) in HIV-infected pregnant women.
methodHIV-infected pregnant women between 14 and 34 weeks gestation received NFV (Cohort 1: 750 mg tid, n = 10; Cohort 2: 1250 mg bid, n = 23) with ZDV and 3TC. Serial blood sampling for NFV concentrations was performed antepartum (AP) and 6 weeks postpartum (PP). Maternal and cord blood samples were also obtained at delivery. NFV and M8 levels were determined by high-performance liquid chromatography. The pharmacokinetic (PK) target was an extrapolated NFV AUC0-24 > 30 mug . h/mL. Mothers were followed frequently for potential clinical and laboratory toxicity.
resultsOverall, NFV in combination with ZDV and 3TC was well tolerated. The PK target was met in 3/8 AP and 5/7 PP in Cohort 1 and 17/21 AP and 16/17 PP in Cohort 2. When Cohort 2 NFV PK parameters AP and PP were compared, median Cmax (3.90 microg/mL vs. 5.01 microg/mL, p < .05) and AUC0-24 (56.6 vs. 86.8 microg . h/mL, p < .05) were increased PP and oral clearance (Cl/F; 44.2 vs. 28.8 L/h, p < .05) was decreased PP. The average M8/NFV ratio was increased PP compared to AP (0.085 vs. 0.29, p < .001). Placental transfer of NFV was low with a median cord blood:maternal plasma ratio at delivery of 0.05. Maternal mean CD4+ T cell counts increased significantly and plasma HIV-1 RNA levels decreased from entry to delivery and 6 to 12 weeks postpartum.
conclusionNFV used in combination with ZDV and 3TC was well tolerated in pregnant HIV-infected women and produced a significant improvement in HIV disease parameters. NFV drug exposure is inadequate in most pregnant women receiving 750 mg tid but is much improved with 1250 mg bid. NFV crosses the placenta poorly. The AP increase in NFV oral clearance and decrease in M8/NFV ratio suggest that CYP3A activity increases relative to CYP2C19 activity during pregnancy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.