A Case Series of Third‐Trimester Raltegravir Initiation: Impact on Maternal HIV‐1 Viral Load and Obstetrical Outcomes

Boucoiran, Isabelle; Tulloch, Karen; Pick, Neora; Kakkar, Fatima; Schalkwyk, Julie van; Money, Deborah; Boucher, Marc

doi:10.1155/2015/731043

Cited by 12 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study supports previously published case reports of rapid decline in HIV-1 viral load after treatment with INSTI-containing regimens. 8,9,11,12 All of the observed ART regimens were effective in decreasing HIV viral load in a relatively short time period, but the addition of an integrase inhibitor suppressed viral load more quickly. This is consistent with prior literature describing the effect of INSTI-based ART in pregnancy, however, a strength of our study is that we compared INSTI- and non-INSTI-containing ART directly.…”

Section: Commentmentioning

confidence: 99%

“…Data from published case series demonstrate rapid reductions in viral load during pregnancy, although no guidelines currently recommend it as a first line therapy to rapidly suppress HIV viral loads among women close to the time of delivery. 8–12 In this study we describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing ART options.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

Rahangdale

Cates

Potter

et al. 2016

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

Background Minimizing time to Human Immunodeficiency Virus (HIV) viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV ribonucleic acid (RNA) in nonpregnant adults. There is limited data in pregnant women. Objective We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing ART options. Study Design We conducted a retrospective cohort study of pregnant HIV-infected women in the U.S. from 2009 to 2015. We included women who initiated antiretroviral therapy (ART), intensified their regimen or switched to a new regimen due to detectable viremia (HIV RNA > 40c/mL) at ≥ 20 weeks gestation. Among women with a baseline HIV RNA permitting one-log reduction, we estimated time to one-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen versus other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. Results This study describes 101 HIV-infected pregnant women from 11 U.S. clinics. Seventy-five percent (76/101) women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. Thirty-nine percent (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting one-log reduction, the median time to one-log RNA reduction was 8 days [Interquartile Range (IQR): 7, 14] in the INSTI group versus 35 days [IQR: 20, 53] in the non-INSTI ART group (p<0.01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to one-log reduction was 7 days [IQR: 6, 10] in the INSTI group versus 11 days [IQR: 10, 14] in the non-INSTI group (p<0.01). Conclusion ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV-RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.

show abstract

Section: Commentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

Rahangdale

Cates

Potter

et al. 2016

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

show abstract

“…This drug has also increasingly been used and effectively as intensification of AT in pregnant women with bad control of infection in late stages of pregnancy [3,[5][6][7]10,11]. In addition, its inclusion in treatment guidelines as elective therapy in adults and since a high proportion of pregnancys are unplanned, an increase in use of INIs in pregnant women may be anticipated.…”

Section: Methodsmentioning

confidence: 99%

“…The risk of MTCT mainly depends on the gestational age at which AT is initiated and the maternal plasma VL at the time of delivery [2,4,5], and therefore achieving virological suppression previously, is the main objective of AT during pregnancy [2,[6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness and safety of integrase inhibitors in HIV-infected pregnant women followed up in the Madrid Cohort

Ramos

Mazariegos

Beceiro

et al. 2019

Preprint

View full text Add to dashboard Cite

Background The risk of HIV-1 mother-to-child transmission (MTCT) is associated mainly with the gestational age at which antiretroviral therapy (AT) begins and HIV-1-RNA viral load (VL) at delivery. The importance of achieving virological supression during pregnancy, has led to an increased use of integrase inhibitors (INIs) in risky conditions. Our objective was to assess the safety and effectiveness in Madrid-Cohort of mothers-children exposed to INIs during pregnancy. Methods Retrospective, multicentric, observational, cohort study, of HIV-1-infected pregnant women exposed to INIs during pregnancy and their infants, from 2000 to 2017, from the nine public hospitals belonging to the Madrid Cohort. Maternal demographic characteristics, clinical data, HIV-1 infection features, AT regimens and changes of treatment during pregnancy were recorded. Blood count, biochemistry panel, HIV-1 VL and CD4+ lymphocyte counts/percentage at first trimester and at the last one near delivery were also collected. Results Sixty seven pregnant women exposed to INIs from the Madrid cohort (n: 1423) and their 68 children were identified (17.6% premature). Neonatal prophylaxis consited mostly on zidovudine (AZT) monotherapy, followed by combined prophylaxis with ‘triple therapy’. There were no cases of MTCT. Twenty women were diagnosed with HIV-1 in the current pregnancy. Of 43 women with AT before pregnancy, 65% received INI before conception. Raltegravir was the most commonly used (80.5%). The median lenght with INI at delivery was 148 days [interquartile rang (IR): 29-251]. Median CD4+ lymphocyte count increased from 428 cells/mL (IR: 310-642) in first trimester to 636 cells/mL (IR: 408-818) in the third. There was a statistically significant increase (p=0.02) of mothers with undetectable VL at delivery compared with first trimester. INIs were well tolerated, without any relevant adverse effect notification. There was no case of discontinued medication due to intolerance or toxicity. 11,7% of children had minor birth defects and one patient had ventricular septal defect without hemodynamic compromise. All of them evolved favourably. Conclusions INI seems safe and effective in prevention of MTCT. Antiretroviral regimens during pregnancy that include INI are increasingly being used. Our findings support the use of INI as intensification in pregnant women at high risk of MTCT.

show abstract

“…While RLT is not licensed for use in pregnancy, there are increasing clinical observational data (27)(28)(29)(30)(31)(32)(33), and guidelines mention its use to prevent MTCT (34,35). Although there are limited data regarding the use of RLT in pregnancy, there is increasing evidence of its efficacy to rapidly reduce maternal HIV-1 viral load in association with other antiretrovirals late in pregnancy (36). Its good placental transfer also allows for preexposure prophylaxis.…”

mentioning

confidence: 99%

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

Vinot

Tréluyer

Giraud

et al. 2016

Antimicrob Agents Chemother

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

A Case Series of Third‐Trimester Raltegravir Initiation: Impact on Maternal HIV‐1 Viral Load and Obstetrical Outcomes

Cited by 12 publications

References 30 publications

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

Effectiveness and safety of integrase inhibitors in HIV-infected pregnant women followed up in the Madrid Cohort

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

Contact Info

Product

Resources

About