Raltegravir Concentrations in the Genital Tract of HIV-1-Infected Women Treated with a Raltegravir-Containing Regimen (DIVA 01 Study)

Clavel, C; Peytavin, Gilles; Tubiana, Roland; Soulié, Cathia; Crenn‐Hébert, Catherine; Heard, Isabelle; Bissuel, F.; Ichou, Houria; Ferreira, Claudia; Katlama, Christine; Marcelin, Anne–Geneviève; Mandelbrot, Laurent

doi:10.1128/aac.01460-10

Cited by 33 publications

(33 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CSF levels have been associated with plasma concentrations, with the extent of blood--brain barrier impairment and with single nucleotide polymorphisms in the gene encoding for ABCG2 (present at the blood--CSF barrier) [19]; they were above IC 50 in most of the patients but above IC 95 in 23.8% of them [18,20]. Raltegravir concentrations in the genital tract were high both in HIV-positive male (seminal plasma being 2.26 --3.25 times higher than plasma levels) and female patients (cervicovaginal fluid being 2.3 times higher than plasma levels) [21,22]. Raltegravir readily crossed the placenta, with a median cord blood/maternal delivery plasma raltegravir concentration ratio~of 1.5 (range, 0.32 --4.33); its elimination was highly variable and extremely prolonged in some infants ranging from 9.3 to 184 h [23].…”

Section: Penetration Into Organs and Tissuesmentioning

confidence: 94%

Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients

Calcagno

D’Avolio

Bonora

2015

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

show abstract

Section: Penetration Into Organs and Tissuesmentioning

confidence: 94%

Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients

Calcagno

D’Avolio

Bonora

2015

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

show abstract

“…Raltegravir is not metabolized through the cytochrome p450 enzyme system and therefore has the advantage of lacking the potential for drug-drug interactions. Recent data also suggest that raltegravir may penetrate the genital tract well and prevents HIV entry into CD4 cells or integration with host DNA, thus having hypothetical advantages for nPEP [25].…”

Section: Alternative Postexposure Prophylaxis Regimensmentioning

confidence: 95%

Postexposure prophylaxis for HIV following sexual exposure

Barber

Benn

2010

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

show abstract

“…There are clinical data showing high cord-to-maternal (C/M) serum ratios at delivery on the order of 1 (14-18). Moreover, RLT penetrates well into the genital tract, with a cervicovaginal fluid-to-blood plasma ratio of 2.3 (19). This study is the first to investigate the bidirectional placental transfer of RLT using the ex vivo human perfusion model, which reproduces the conditions of the third trimester of pregnancy (20).…”

mentioning

confidence: 99%

Bidirectional Transfer of Raltegravir in an Ex Vivo Human Cotyledon Perfusion Model

Vinot

Tréluyer

Giraud

et al. 2016

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

i Placental transfer of the HIV integrase inhibitor raltegravir (RLT) was investigated in term human cotyledons in the maternalto-fetal (n ‫؍‬ 3) and fetal-to-maternal (n ‫؍‬ 6) directions. In the maternal-to-fetal direction, the mean ؎ standard deviation (SD) fetal transfer rate (FTR) was 9.1% ؎ 1.4%, and the mean ؎ SD clearance index (IC), i.e., RLT FTR/antipyrine FTR, was 0.28 ؎ 0.05. In the fetal-to-maternal direction, the mean ؎ SD CI was 0.31 ؎ 0.09. Placental transfer of RLT was high in both directions.A ntiretroviral therapy (ART), in addition to its benefits for the health of people living with HIV, is effective for preventing mother-to-child transmission (MTCT) of HIV-1, which in industrialized countries has been reduced to Ͻ1% (1-3). Raltegravir (RLT) belongs to the integrase strand transfer inhibitor (INSTI) class of antiretroviral agents, which act by blocking the insertion of viral cDNA into human genomic DNA (4). RLT is classified in category C by the Food and Drug Administration (FDA), meaning that fetal risk has been detected in animal reproduction studies, but there have been no adequate studies conducted in pregnant women. The placental transfer of currently used antiretrovirals varies considerably between classes and individual molecules, and nucleoside reverse transcriptase inhibitors (NRTIs) have high placental transfer (5, 6), whereas protease inhibitors have lower placental transfer (7,8). The purpose of this study was to investigate the bidirectional placental transfer of RLT by using the ex vivo model of the human perfused cotyledon.Nine term placentas from normal pregnancies (from 38 to 42 weeks of gestational age) were obtained from Louis Mourier Hospital (Colombes, France). All mothers were seronegative for HIV infection and hepatitis B and C, and they had taken no medication other than oxytocin or epidural anesthesia during labor. Written informed consent was obtained for all placentas. RLT base was provided by Merck (Paris, France), antipyrine-phosphate-buffered saline (PBS) was purchased from Sigma-Aldrich (SaintQuentin-Fallavier, France), and other chemicals were from Invitrogen (Cergy-Pontoise, France).Placentas were perfused in an open double-circuit system, as previously described (9). Perfusion experiments were started within 20 min after delivery. After visual examination, an intact cotyledon was selected, and a truncal branch of the chorionic artery and the associated vein were cannulated; the establishment of venous flow after perfusion of the fetal artery flow confirmed the viability of the cotyledon. On the maternal side, the perfused area progressively whitened, allowing visualization of the cotyledon. The cotyledon was placed into the perfusion chamber and maintained at 37°C, with the maternal side upward. The intervillous space on the maternal side was perfused by two needles piercing the basal plate. The two circuits were pumped separately by peristaltic pumps. The fetal and maternal flows were 6 and 12 ml/min, respectively, and the perfusion length was 90 min. The p...

show abstract

Raltegravir Concentrations in the Genital Tract of HIV-1-Infected Women Treated with a Raltegravir-Containing Regimen (DIVA 01 Study)

Cited by 33 publications

References 17 publications

Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients

Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients

Postexposure prophylaxis for HIV following sexual exposure

Bidirectional Transfer of Raltegravir in an Ex Vivo Human Cotyledon Perfusion Model

Contact Info

Product

Resources

About