A Randomized Controlled Trial to Assess Safety, Tolerability, and Antepartum Viral Load with Increased Lopinavir/Ritonavir Dosage in Pregnancy

Bonafé, Simone Martins; Costa, da; Vaz, Maria José Rodrigues; Senise, Jorge Figueiredo; Pott-Júnior, Henrique; Machado, Rachel Helena Vieira; Castelo, Adauto

doi:10.1089/apc.2013.0159

Cited by 11 publications

(15 citation statements)

References 32 publications

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“…31-33 Two randomized studies of standard versus increased dose lopinavir in pregnancy suggest that increased lopinavir doses may be beneficial for pregnant women with a detectable viral load at initiation of treatment in pregnancy or with detectable lopinavir resistance mutations. 34,35 The package insert for atazanavir, the only protease inhibitor approved in the US for use in pregnancy, includes a recommendation for an increased dose for treatment-experienced pregnant women in the second or third trimester who are also receiving tenofovir or an H 2 -receptor antagonist, which have been shown to reduce atazanavir exposure. 36 There are no data on darunavir pharmacokinetics or clinical outcomes with use of an increased dose in pregnancy, and an increased twice daily darunavir dose (800 mg or 900 mg darunavir with 100 mg ritonavir) is currently under study in another arm of P1026s.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women

Stek

Best

Wang

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective To describe darunavir pharmacokinetics with once and twice daily dosing during pregnancy and postpartum in HIV-infected women. Design Women were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective, non-blinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving darunavir/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily. Methods Intensive steady-state 12 or 24 hour pharmacokinetic profiles were performed during the second trimester, third trimester and postpartum. Darunavir was measured using high performance liquid chromatography (detection limit: 0.09 μg/mL). Results Pharmacokinetic data were available for 64 women (30 once daily and 34 twice daily dosing). Median darunavir area under the concentration-time curve (AUC) and maximum concentration (Cmax) were significantly reduced during pregnancy with both dosing regimens compared to postpartum, while the last measurable concentration (Clast) was also reduced during pregnancy with once daily darunavir. Darunavir AUC with once daily dosing was reduced by 38% during the second trimester and by 39% during the third trimester. With twice daily dosing, darunavir AUC was reduced by 26% in both trimesters. The median (range) ratio of cord blood/maternal delivery darunavir concentration in 32 paired samples was 0.18 (range: 0 – 0.82). Conclusion Darunavir exposure is reduced by pregnancy. In order to achieve darunavir plasma concentrations during pregnancy equivalent to those seen in non-pregnant adults, an increased twice daily dose may be necessary. This may be especially important for treatment-experienced women who may have developed antiretroviral resistance mutations.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women

Stek

Best

Wang

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…43 To further elucidate the differences between standard and increased doses of lopinavir in pregnancy, a separate trial randomized 32 pregnant women to the standard dose and 31 women to the increased dose at gestational ages between 14 and 33 weeks. 44 The frequency of adverse events was comparable between the groups. Among women with baseline viral load >50 copies/mL assigned to the standard dose group, 45% had an antepartum (within the last 4 weeks of pregnancy) viral load >50 copies/mL; for those who were assigned to the increased dose group, only 10.5% had an antepartum viral load >50 copies/mL.…”

Section: Pharmacokinetics Of Ritonavir-boosted Regimens In Pregnancymentioning

confidence: 84%

Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

Salama

Eke

Best

et al. 2020

The Journal of Clinical Pharma

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Pharmacokinetic boosting of antiretroviral (ARV) therapies with either ritonavir or cobicistat is used to achieve target drug exposure, lower pill burden, and provide simplified dosing schedules. Several ARVs require boosting, including the integrase inhibitor elvitegravir as well as protease inhibitors such as darunavir, atazanavir, and lopinavir. The use of boosted regimens in pregnant women living with HIV has been studied for a variety of ARVs; however, a recent recommendation by the US Food and Drug Administration advised against cobicistat-boosted regimens in pregnancy due to substantially lower drug exposures observed in clinical pharmacokinetic studies. The objectives of this article are to review pharmacokinetic enhancement of ARVs with ritonavir and cobicistat during pregnancy and postpartum, describe clinical implications, and provide recommendations for future research.

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“…Other studies reported the incidence of dyslipidaemia expressed in severity scores of adverse events - Grade I, TC 200 to <240 mg/dl or TG 150–300 mg/dl; Grade II TC 240 to <300, TG >300 to 500; Grade III TC ≥ 300 or TG >500 to <1000, and Grade IV TG >1000 mg/dl – and mostly found cases of lower grades of dyslipidaemia [ 33 , 34 , 36 , 37 , 43 , 44 ]. Duran et al [ 37 ] found dyslipidaemia cases in all treatment groups and two cases (0.6%) hypertriglyceridemia grade II in patients receiving first generation PI nelfinavir.…”

Section: Resultsmentioning

confidence: 99%

The association between HIV (treatment), pregnancy serum lipid concentrations and pregnancy outcomes: a systematic review

et al. 2017

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BackgroundObserved adverse effects of antiretroviral therapy (ART) on the lipid profile could be of significance in pregnancy. This systematic review aims to summarize studies that investigated the association between HIV, ART and serum lipids during pregnancy and adverse pregnancy outcomes.MethodsA systematic search was conducted in five electronic databases to obtain articles that measured serum lipid concentrations or the incidence of dyslipidaemia in HIV-infected pregnant women. Included articles were assessed for quality according to the Cochrane Risk of Bias Tool. The extracted data was analysed through descriptive analysis.ResultsOf the 1264 articles screened, 17 articles were included in this review; eleven reported the incidence of dyslipidaemia, and twelve on maternal serum lipid concentrations under the influence of HIV-infection and ART. No articles reported pregnancy outcomes in relation to serum lipids. Articles were of acceptable quality, but heterogenic in methods and study design. Lipid levels in HIV-infected women increased 1.5–3 fold over the trimesters of pregnancy, and remained within the physiological reference range. The percentage of women with dyslipidaemia was variable between the studies [0–88.9%] and highest in the groups on first generation protease inhibitors and for women on ART at conception.ConclusionThis systematic review observed physiologic concentrations of serum lipids for HIV-infected women receiving ART during pregnancy. Serum lipids were increased in users of first generation protease inhibitors and for those on treatment at conception. There was no information available about pregnancy outcomes. Future studies are needed which include HIV-uninfected control groups, control for potential confounders, and overcome limitations associated with included studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2581-8) contains supplementary material, which is available to authorized users.

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A Randomized Controlled Trial to Assess Safety, Tolerability, and Antepartum Viral Load with Increased Lopinavir/Ritonavir Dosage in Pregnancy

Cited by 11 publications

References 32 publications

Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women

Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women

Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

The association between HIV (treatment), pregnancy serum lipid concentrations and pregnancy outcomes: a systematic review

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