Rilpivirine in HIV-1-positive women initiating pregnancy: to switch or not to switch?

Abstract

Background Safety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy. Objectives To describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC. Methods In the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC. Results Among 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred. Conclusions In virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes.

Hydrophobic Pocket Occupation Design of Difluoro-Biphenyl-Diarylpyrimidines as Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors: from N-Alkylation to Methyl Hopping on the Pyrimidine Ring

“…Reported claimed plasma concentrations of RPV were reduced that was closely related to the drug metabolism during second/third trimesters of pregnancy, with exposed a potential risk of viral breakthroughs. , Hence, the toxicity issue should be taken into consideration in pregnancy. A single-dose acute toxicity study of 16y was carried out in the healthy and pregnant mouse model.…”

“…However, its cytotoxity limited further evalutions probably due to the metabolites of dimethyl biphenyl moiety. 6 Compound 4 with replacement of the dimethyl groups by a difluoro moiety maintained the antivial activity, especially exhibiting much lower cytotoxicity (SI > 23,8095). Futhermore, a series of biphenyl-DAPYs compounds (5-7) with differernt CH-R linkers (R = OH, 10 CN 7 and NOH 11 ) were also developed in our group by adjusting the flexibility of the molecules to adopt the RT enzyme.…”

Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004–2020: A surveillance study

“…Indeed, guidelines that recommended changing a rilpivirine-based ARV treatment during pregnancy in fully suppressed women was shown to increase the risk of viral rebound. 14,15 Since 2007, the HHS and Canadian guidelines recommend that women who are on a fully suppressive ARV treatment before pregnancy continue this treatment in pregnancy, regardless of whether it is preferred or alternative, unless a risk for fetal toxicity or virological failure is suspected. [4][5][6][7] However, if ARV treatment requires changing, it appears important that this change be made early in pregnancy.…”

“…Changing ARV treatment solely because of pregnancy does not always lead to better treatment outcomes. Indeed, guidelines that recommended changing a rilpivirine‐based ARV treatment during pregnancy in fully suppressed women was shown to increase the risk of viral rebound 14,15 . Since 2007, the HHS and Canadian guidelines recommend that women who are on a fully suppressive ARV treatment before pregnancy continue this treatment in pregnancy, regardless of whether it is preferred or alternative, unless a risk for fetal toxicity or virological failure is suspected 4–7 .…”

Druggability modification strategies of the diarylpyrimidine‐type non‐nucleoside reverse transcriptase inhibitors

“…However, with comparison of its high in vitro potency, the original form of RPV was limited by the poor solubility and the F values could not be accurately measured which was pH dependent 101 . Plasma concentrations of RPV were reduced that was closely related to the drug metabolism during second/third trimesters in pregnancy, with exposed a potential risk of viral breakthroughs 102 . In terms of these limitations/drawbacks, several strategies to improve the solubility/efficacy will be introduced.…”