Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum

Lamorde, Mohammed; Wang, Xinzhu; Neary, Megan; Bisdomini, Elisa; Nakalema, Shadia; Byakika-Kibwika, Pauline; Mukonzo, Jackson; Khan, Waheed; Owen, Andrew; McClure, Myra O.; Boffito, Marta

doi:10.1093/cid/ciy161

Cited by 25 publications

(26 citation statements)

References 13 publications

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“…Pharmacogenetics, which has resulted in patients reacting differently to the same drug dosage, has also resulted in lack of adherence. This was mostly witnessed with EFV, where a considerable number of patients developed central nervous system related ADRs [69,70]. The ENCORE study and many others have provided overwhelming evidence on how pharmacogenetics suggest personalized prescription of drugs [71][72][73][74][75].…”

Section: Factors Affecting Adherence To Art In Sub-saharan Africamentioning

confidence: 99%

Promoting Undetectable Equals Untransmittable in Sub-Saharan Africa: Implication for Clinical Practice and ART Adherence

Thomford

Mhandire

Dandara

et al. 2020

IJERPH

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In the last decade, reliable scientific evidence has emerged to support the concept that undetectable viral loads prevent human immunodeficiency virus (HIV). Undetectable equals untransmissible (U = U) is a simple message that everyone can understand. The success of this concept depends on strict adherence to antiretroviral therapy (ART) and the attainment of suppressed viral loads (VLs). To achieve U = U in sub-Saharan Africa (SSA), poor adherence to ART, persistent low-level viremia, and the emergence of drug-resistant mutants are challenges that cannot be overlooked. Short of a cure for HIV, U = U can substantially reduce the burden and change the landscape of HIV epidemiology on the continent. From a public health perspective, the U = U concept will reduce stigmatization in persons living with HIV (PLWHIV) in SSA and strengthen public opinion to accept that HIV infection is not a death sentence. This will also promote ART adherence because PLWHIV will aim to achieve U = U within the shortest possible time. This article highlights challenges and barriers to achieving U = U and suggests how to promote the concept to make it beneficial and applicable in SSA. This concept, if expertly packaged by policy-makers, clinicians, health service providers, and HIV control programs, will help to stem the tide of the epidemic in SSA.

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Section: Factors Affecting Adherence To Art In Sub-saharan Africamentioning

confidence: 99%

Promoting Undetectable Equals Untransmittable in Sub-Saharan Africa: Implication for Clinical Practice and ART Adherence

Thomford

Mhandire

Dandara

et al. 2020

IJERPH

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“…This would mean more Gag is present, therefore HIV-1 control is suboptimal during pregnancy allowing increased HIV-1 peptide generation. In untreated PP women of African ethnicity a non-significant increase in HIV-1 RNA was observed with gestation, and numerous pharmacokinetic studies indicate pregnancy negatively affects ART levels (53)(54)(55)(56). In an ART interruption study increases in both Gag and Nef CD8 T-cell responses were found with rebounding viraemia (52).…”

Section: Discussionmentioning

confidence: 99%

Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells

et al. 2020

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Pregnancy induces alterations in peripheral T-cell populations with both changes in subset frequencies and anti-viral responses found to alter with gestation. In HIV-1 positive women anti-HIV-1 responses are associated with transmission risk, however detailed investigation into both HIV-1-specific memory responses associated with HIV-1 control and T-cell subset changes during pregnancy have not been undertaken. In this study we aimed to define pregnancy and gestation related changes to HIV-1-specific responses and T-cell phenotype in ART treated HIV-1 positive pregnant women. Eleven non-pregnant and 24 pregnant HIV-1 positive women were recruited, peripheral blood samples taken, fresh cells isolated, and compared using ELISpot assays and flow cytometry analysis. Clinical data were collected as part of standard care, and non-parametric statistics used. Alterations in induced IFNγ, IL-2, IL-10, and granzyme B secretion by peripheral blood mononuclear cells in response to HIV-1 Gag and Nef peptide pools and changes in T-cell subsets between pregnant and non-pregnant women were assessed, with data correlated with participant clinical parameters and longitudinal analysis performed. Cross-sectional comparison identified decreased IL-10 Nef response in HIV-1 positive pregnant women compared to non-pregnant, while correlations exhibited reversed Gag and Nef cytokine and protease response associations between groups. Longitudinal analysis of pregnant participants demonstrated transient increases in Gag granzyme B response and in the central memory CD4 T-cell subset frequency during their second trimester, with a decrease in CD4 effector memory T cells from their second to third trimester. Gag and Nef HIV-1-specific responses diverge with pregnancy time-point, coinciding with relevant T-cell phenotype, and gestation associated immunological adaptations. Decreased IL-10 Nef and both increased granzyme B Gag response and central memory CD4 T cells implies that amplified antigen production is occurring, which suggests a period of compromised HIV-1 control in pregnancy.

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“…EFV 400 mg is expected to be safe for pregnant women to use, like EFV 600 mg. Data from the Tsepamo study in Botswana show that EFV 600 mg is safer in pregnancy than lopinavir/ritonavir (LPV/r) or nevirapine (NVP)-based ART regimens at conception, with safety similar to that of DTG in terms of pregnancy outcomes and no elevated risk of neural tube defects (19). Pharmacokinetic and pharmacodynamic studies suggest that drug concentrations decline slightly with EFV 400 mg but remain within the therapeutic range and are unlikely to result in reduced efficacy (6). It is not advised to use EFV 400 mg and EFV 600 mg in settings with high levels of pretreatment HIV drug resistance.…”

Section: Efv 400 Mg In First-line Artmentioning

confidence: 99%

“…The 2019 updated guidelines provide the latest recommendations based on rapidly evolving evidence of safety and efficacy and programmatic experience using DTG and EFV 400 mg in pregnant women and people coinfected with TB (4)(5)(6). These guidelines provide further reassurance of DTG as the preferred antiretroviral (ARV) drug in firstand second-line regimens due to the declining estimate of neural tube defect risk and observed efficacy.…”

Section: Introductionmentioning

confidence: 99%

Postmarketing Surveillance of Pregnancy Outcomes With Dolutegravir Use

Crawford

Wyk

Aboud

et al. 2020

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: "This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition". Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. Update of recommendations on first-and second-line antiretroviral regimens. Geneva, Switzerland: World Health Organization; 2019 (WHO/CDS/HIV/19.15). Licence: CC BY-NC-SA 3.0 IGO.

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Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum

Cited by 25 publications

References 13 publications

Promoting Undetectable Equals Untransmittable in Sub-Saharan Africa: Implication for Clinical Practice and ART Adherence

Promoting Undetectable Equals Untransmittable in Sub-Saharan Africa: Implication for Clinical Practice and ART Adherence

Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells

Postmarketing Surveillance of Pregnancy Outcomes With Dolutegravir Use

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