Efavirenz-Based Antiretroviral Therapy Reduces Artemether–Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women

ABSTRACT Artemether-lumefantrine is often coadministered with efavirenz-based antiretroviral therapy for malaria treatment in HIV-infected women during pregnancy. Previous studies showed changes in lumefantrine pharmacokinetics due to interaction with efavirenz in nonpregnant adults. The influence of pregnancy on this interaction has not been reported. This pharmacokinetic study involved 35 pregnant and 34 nonpregnant HIV-malaria-coinfected women receiving efavirenz-based antiretroviral therapy and was conducted in four health facilities in Nigeria. Participants received a 3-day standard regimen of artemether-lumefantrine for malaria treatment, and intensive pharmacokinetic sampling was conducted from 0.5 to 96 h after the last dose. Plasma efavirenz, lumefantrine, and desbutyl-lumefantrine were quantified using validated assays, and pharmacokinetic parameters were derived using noncompartmental analysis. The median middose plasma concentrations of efavirenz were significantly lower in pregnant women (n = 32) than in nonpregnant women (n = 32) at 1,820 ng/ml (interquartile range, 1,300 to 2,610 ng/ml) versus 2,760 ng/ml (interquartile range, 2,020 to 5,640 ng/ml), respectively (P = 0.006). The lumefantrine area under the concentration-time curve from 0 to 96 h was significantly higher in pregnant women (n = 27) at 155,832 ng · h/ml (interquartile range, 102,400 to 214,011 ng · h/ml) than nonpregnant women at 90,594 ng · h/ml (interquartile range, 58,869 to 149,775 ng · h/ml) (P = 0.03). A similar trend was observed for the lumefantrine concentration at 12 h after the last dose of lumefantrine, which was 2,870 ng/ml (interquartile range, 2,180 to 4,880 ng/ml) versus 2,080 ng/ml (interquartile range, 1,190 to 2,970 ng/ml) in pregnant and nonpregnant women, respectively (P = 0.02). The lumefantrine-to-desbutyl-lumefantrine ratio also tended to be lower in pregnant women than in nonpregnant women (P = 0.076). Overall, pregnancy tempered the extent of efavirenz-lumefantrine interactions, resulting in increased lumefantrine exposure. However, any consideration of dosage adjustment for artemether-lumefantrine to enhance exposure in this population needs to be based on data from a prospective study with safety and efficacy endpoints.

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Faculty Opinions recommendation of Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3043961.2725059 ◽

2010 ◽

Author(s):

Lynne Mofenson

Keyword(s):

Antiretroviral Therapy ◽

Pregnant Women ◽

Increased Risk

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ACE2, TMPRSS2 and L-SIGN expression in placentae from HIV-positive pregnancies exposed to antiretroviral therapy–implications for SARS-CoV-2 placental infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab166 ◽

2021 ◽

Author(s):

Smriti Kala ◽

Ksenia Meteleva ◽

Lena Serghides

Keyword(s):

Antiretroviral Therapy ◽

Pregnant Women ◽

Viral Entry ◽

Cell Entry ◽

Hiv Positive ◽

Mrna Levels ◽

Black Race ◽

Entry Receptor ◽

Lower Expression ◽

Human Placentae

Abstract Background SARS-CoV-2 binding receptor ACE2 and the spike protein priming protease TMPRSS2 are co-expressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART). Methods We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2 and L-SIGN (an alternative entry receptor) by qPCR in 105 placentae: 45 from pregnant women with HIV (WHIV) exposed to protease inhibitor (PI)-based ART, 17 from WHIV on non-PI-based ART, and 43 from HIV-uninfected women. Results ACE2 levels were lower, while L-SIGN levels were higher in placentae from WHIV on PI-based ART as compared to those on non-PI-based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses. Discussion We have identified pregnant women of Black race and WHIV who are on PI-based ART to have relatively lower expression of placental ACE2 than those of White race and HIV-uninfected women. This effect may potentially contribute to altered susceptibility to COVID-19 in these women, either favorably; by reduced viral entry, or detrimentally; by loss of ACE2 protection against hyperinflammation.

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231 The effect of antiretroviral therapy regimens on gestational weight gain in pregnant women with HIV

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2020.12.253 ◽

2021 ◽

Vol 224 (2) ◽

pp. S152-S153

Author(s):

Naima T. Joseph ◽

Glen Satten ◽

Rachel Williams ◽

Martina Badell ◽

Anandi Sheth

Keyword(s):

Weight Gain ◽

Antiretroviral Therapy ◽

Pregnant Women ◽

Gestational Weight Gain ◽

Gestational Weight ◽

Women With Hiv

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Social Vulnerability among Foreign-Born Pregnant Women and Maternal Virologic Control of HIV

American Journal of Perinatology ◽

10.1055/s-0040-1721714 ◽

2020 ◽

Author(s):

Ashish Premkumar ◽

Lynn M. Yee ◽

Lia Benes ◽

Emily S. Miller

Keyword(s):

Antiretroviral Therapy ◽

Pregnant Women ◽

Median Time ◽

Social Vulnerability ◽

Viral Suppression ◽

Foreign Born ◽

Women Living With Hiv ◽

Virologic Control ◽

Clinical Records ◽

Living With Hiv

Objective The aim of this study was to assess whether social vulnerability among foreign-born pregnant women living with HIV is associated with maternal viremia during pregnancy. Study Design This retrospective cohort study included all foreign-born pregnant women living with HIV who received prenatal care in a multidisciplinary prenatal clinic between 2009 and 2018. A licensed clinical social worker evaluated all women and kept detailed clinical records on immigration status and social support. Social vulnerability was defined as both living in the United States for less than 5 years and reporting no family or friends for support. The primary outcome was evidence of viral non-suppression after achievement of initial suppression. Secondary outcomes were the proportion of women who required > 12 weeks after starting antiretroviral therapy to achieve viral suppression, median time to first viral suppression (in weeks) after initiation of antiretroviral therapy, and the proportion who missed ≥ 5 doses of antiretroviral therapy. Bivariable analyses were performed. Results A total of 111 foreign-born women were eligible for analysis, of whom 25 (23%) were classified as socially vulnerable. Social and clinical characteristics of women diverged by social vulnerability categorization but no differences reached statistical significance. On bivariable analysis, socially-vulnerable women were at increased risk for needing > 12 weeks to achieve viral suppression (relative risk: 1.78, 95% confidence interval: 1.18–2.67), though there was no association with missing ≥ 5 doses of antiretroviral therapy or median time to viral suppression after initiation of antiretroviral therapy. Conclusion Among foreign-born, pregnant women living with HIV, markers of virologic control during pregnancy were noted to be worse among socially-vulnerable women. Insofar as maternal viremia is the predominant driver of perinatal transmission, closer clinical surveillance and support may be indicated in this population. Key Points

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Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women

Malaria Journal ◽

10.1186/s12936-017-1914-9 ◽

2017 ◽

Vol 16 (1) ◽

Cited By ~ 15

Author(s):

Ritah F. Mutagonda ◽

Appolinary A. R. Kamuhabwa ◽

Omary M. S. Minzi ◽

Siriel N. Massawe ◽

Muhammad Asghar ◽

...

Keyword(s):

Treatment Outcome ◽

Pregnant Women ◽

Malaria Treatment

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Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure

AIDS ◽

10.1097/qad.0b013e32832e34b1 ◽

2009 ◽

Vol 23 (18) ◽

pp. 2425-2430 ◽

Cited By ~ 30

Author(s):

David W Ouyang ◽

David E Shapiro ◽

Ming Lu ◽

Susan B Brogly ◽

Audrey L French ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Pregnant Women ◽

Increased Risk

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Treating pregnant women with highly active antiretroviral therapy

Future HIV Therapy ◽

10.2217/17469600.1.2.215 ◽

2007 ◽

Vol 1 (2) ◽

pp. 215-222

Author(s):

Katherine M Coyne ◽

Rachael Jones ◽

David Hawkins

Keyword(s):

Antiretroviral Therapy ◽

Pregnant Women ◽

Highly Active Antiretroviral Therapy ◽

Highly Active

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Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis

PLoS Medicine ◽

10.1371/journal.pmed.1002579 ◽

2018 ◽

Vol 15 (6) ◽

pp. e1002579 ◽

Cited By ~ 18

Author(s):

Frank Kloprogge ◽

Lesley Workman ◽

Steffen Borrmann ◽

Mamadou Tékété ◽

Gilbert Lefèvre ◽

...

Keyword(s):

Young Children ◽

Pregnant Women ◽

Meta Analysis ◽

Malaria Treatment

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Persistent Chlamydia trachomatis, Neisseria gonorrhoeae or Trichomonas vaginalis positivity after treatment among human immunodeficiency virus-infected pregnant women, South Africa

International Journal of STD & AIDS ◽

10.1177/0956462419898612 ◽

2020 ◽

Vol 31 (4) ◽

pp. 294-302 ◽

Cited By ~ 1

Author(s):

Andrew Medina-Marino ◽

Maanda Mudau ◽

Noah Kojima ◽

Remco PH Peters ◽

Ute D Feucht ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Chlamydia Trachomatis ◽

Neisseria Gonorrhoeae ◽

Antenatal Care ◽

Pregnant Women ◽

Trichomonas Vaginalis ◽

Repeat Testing ◽

Care Visit ◽

Immunodeficiency Virus

The objective of this study is to assess the predictors and frequency of persistent sexually transmitted infection (STI) positivity in human immunodeficiency virus (HIV)-infected pregnant women treated for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) or Trichomonas vaginalis (TV) infection. We enrolled HIV-infected pregnant women attending their first antenatal care visit and tested them for urogenital CT, NG and TV infection using Xpert® CT/NG and TV assays (Cepheid, Sunnyvale, CA). Those testing positive were treated. Participants either notified partners to seek treatment or were given extra medication to deliver to partners for treatment. Repeat testing was conducted approximately 21 days post-treatment or treatment initiation. Among 427 participants, 172 (40.3%) tested positive for any STI. Of the 136 (79.1%) that returned for repeat testing, 36 (26.5%) tested positive for the same organism: CT = 27 (26.5%), NG = 1 (6.3%), TV = 11 (16.7%). Persistent CT positivity was independently associated with having more than one sex partner in the preceding 12 months (adjusted-prevalence ratio [aPR] = 3.03, 95% CI: 1.44–6.37) and being newly diagnosed with HIV infection during the first antenatal care visit compared to those currently on antiretroviral therapy (aPR = 3.97, 95% CI: 1.09–14.43). Persistent TV positivity was associated with not knowing if a partner sought treatment following STI disclosure (aPR = 12.6, 95% CI: 2.16–73.5) and prior diagnosis of HIV but not currently on antiretroviral therapy. (aPR = 4.14; 95% CI: 1.25–13.79). We identified a high proportion of HIV-infected pregnant women with persistent CT or TV positivity after treatment. To decrease the risk of re-infection, enhanced strategies for partner treatment programmes are needed to improve the effectiveness of STI screening and treatment in pregnancy. The relationship between not being on antiretroviral therapy and persistent STI positivity needs further study.

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