Protease inhibitors and preterm delivery

Favarato, Graziella; Townsend, Claire L; Bailey, Heather; Peters, Helen; Tookey, P; Taylor, Graham P.; Thorne, Claire

doi:10.1097/qad.0000000000001694

Cited by 41 publications

(45 citation statements)

References 34 publications

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“…The same group found no difference in PTD rates in a retrospective study comparing lopinavir/r and atazanavir/r as the third agent in cART . The latest publication from the NSHPC suggests that atazanavir/r has a lower PTD rate than lopinavir/r, particularly in women with a CD4 count <350 cells/mm 3 and compared to darunavir/r in women initiating cART in pregnancy .…”

Section: Current Issues In the Use Of Art In Pregnancy And Pregnanmentioning

confidence: 99%

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

et al. 2019

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Section: Current Issues In the Use Of Art In Pregnancy And Pregnanmentioning

confidence: 99%

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

et al. 2019

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“…Many anti-HIV drugs interfere directly with the viral life cycle by targeting key viral enzymes [1], e.g., reverse transcriptase inhibitors [2,3], integrase inhibitors [4,5], and protease inhibitors [6,7]. While such efforts are already hampered by the emergence of drug resistance mutations in the enzymes (e.g., in [8]), the scenario further worsens when viral enzyme substrates, such as Gag (HIV protease substrate), are found to synergistically contribute to drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs

Koh

Gan

2019

Molecules

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HIV protease inhibitors against the viral protease are often hampered by drug resistance mutations in protease and in the viral substrate Gag. To overcome this drug resistance and inhibit viral maturation, targeting Gag alongside protease rather than targeting protease alone may be more efficient. In order to successfully inhibit Gag, understanding of its drug resistance mutations and the elicited structural changes on protease binding needs to be investigated. While mutations on Gag have already been mapped to protease inhibitor resistance, there remain many mutations, particularly the non-cleavage mutations, that are not characterized. Through structural studies to unravel how Gag mutations contributes to protease drug resistance synergistically, it is thus possible to glean insights to design novel Gag inhibitors. In this review, we discuss the structural role of both novel and previously reported Gag mutations in PI resistance, and how new Gag inhibitors can be designed.

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“…Until recently, international and French guidelines recommended the use of two nucleoside reverse transcriptase inhibitors (NRTI), namely emtricitabine plus tenofovir disoproxil fumarate (TDF/FTC) or abacavir plus lamivudine (ABC/3TC) in combination with a ritonavir-boosted protease inhibitor (bPI), as preferred regimen during pregnancy [11–13]. The availability of integrase strand-transfer inhibitors (INSTI), together with some concerns about a potential association between the use of bPI and premature delivery [14–16], could be a “game changer” in the field of cART during pregnancy. Indeed, the ability of INSTI to rapidly control HIV replication is very appealing [17, 18], especially in late presenting women (i.e.…”

Section: Introductionmentioning

confidence: 99%

“Real life” use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study

et al. 2019

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Introduction Limited “real life” data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting. Methods HIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns. Results We included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6. Conclusions RAL appears safe and effective in this “real-life” study. No defect and no HIV transmission was reported in new-borns.

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Protease inhibitors and preterm delivery

Abstract: Our data support a link between the initiation of RTV-boosted/lopinavir-based ART preconception and PTD in subsequent pregnancies, with implications for treatment guidelines. Continued monitoring of PTD risk is needed as increasing numbers of pregnancies are conceived on new drugs.

Cited by 41 publications

References 34 publications

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs

“Real life” use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study

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