Evidence map›Paper›PMID 25878720›Full record

ArticleAIDS research and therapy2015

Cytochrome P450 2B6 genetic variants are associated with plasma nevirapine levels and clinical response in HIV-1 infected Kenyan women: a prospective cohort study.

Margaret Ngwono Oluka, Faith Apolot Okalebo, Anastasia Nkatha Guantai, R Scott McClelland, Susan M Graham

Open access · goldAbstract read
In one paragraph

Article in AIDS research and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 22 citations in OpenAlex.

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  5. Association ofPharmacogenomics and personalized medicine · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Margaret Ngwono OlukaDepartment of Pharmacology and Pharmacognosy, University of Nairobi, P.O. BOX 19498, Nairobi, 00202 Kenya.
Faith Apolot OkaleboDepartment of Pharmacology and Pharmacognosy, University of Nairobi, P.O. BOX 19498, Nairobi, 00202 Kenya.
Anastasia Nkatha GuantaiDepartment of Pharmacology and Pharmacognosy, University of Nairobi, P.O. BOX 19498, Nairobi, 00202 Kenya.
R Scott McClellandDepartments of Medicine, Global Health, and Epidemiology, University of Washington, Seattle, USA and Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya.
Susan M GrahamDepartments of Medicine, Global Health, and Epidemiology, University of Washington, Seattle, USA and Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya.
University of Nairobi · KEUniversity of Washington · US

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
EARLY INFECTION IN WOMEN EXPOSED MUCOSALLY TO HIV-1R37AI038518 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI OVERBAUGH, JULIE M. · 1999 to 2019
$12.9M
Antiretroviral Therapy and HIV-1 Infectivity in WomenR01AI058698 · NIAID · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, RAYMOND SCOTT · 2005 to 2010
$2.8M
Genital HIV-1 Shedding among Women Starting Second-Line Antiretroviral TherapyK23AI069990 · NIAID · UNIVERSITY OF WASHINGTON · PI GRAHAM, SUSAN MARIE · 2006 to 2010
$633k
Antiretroviral Therapy and HIV-1 Infectivity in WomenR56AI058698 · NIAID · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, RAYMOND SCOTT · 2011 to 2011
$390k
NIAID NIH HHS K23 AI069990NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI058698NIAID NIH HHS R37 AI038518NIAID NIH HHS R56 AI058698
6 · The paper itself

Abstract

backgroundPolymorphisms in cytochrome P450 2B6 (CYP2B6) affect the steady state plasma concentration of nevirapine. CYP2B6 516G>T and 983T>C are common in African populations, but data on their influence on plasma nevirapine concentration and clinical response in African women are limited. We investigated the impact of CYP 516G>T and 983T>C on plasma nevirapine concentration and clinical outcomes in a prospective cohort study of HIV-infected Kenyan women.

methodsStudy subjects were 66 HIV-1-seropositive women taking nevirapine-based antiretroviral therapy. Plasma collected at week 12 was analyzed for nevirapine concentration by high performance liquid chromatography. Baseline samples were genotyped for CYP2B6 516G>T and 983T>C single nucleotide polymorphisms by real-time polymerase chain reaction. CD4 cell count, plasma viral load, and genotypic drug resistance in plasma and genital secretions were assessed at baseline and during follow up. We evaluated the effect of each genotype on plasma nevirapine concentration at week 12 and on change in CD4 cell count at months 3, 6 and 12. Associations between plasma nevirapine concentration and clinical outcomes were analyzed by logistic or linear regression.

resultsWomen with CYP2B6 516TT genotype (n=9) had higher mean nevirapine plasma levels (14.33 μg/mL) compared to those with heterozygous 516GT (9.18 μg/mL; n=25) and wild- type 516GG (7.95 μg/mL; n=32) genotypes (P=0.01). Women heterozygous for the CYP2B6 983TC genotype (n=13) had higher mean nevirapine plasma levels (12.94 μg/mL), compared to women with the homozygous 983TT (8.35 μg/mL; n=53) genotype (P=0.007). In Generalized Estimating Equation analysis, plasma nevirapine levels predicted greater change in CD4 cell count after ART initiation (adjusted beta 119.4 cells/μL, 95% CI, 27.3-211.5 cells/μL, P=0.01). The CYP2B6 983TT genotype also predicted greater change in CD4 cell count (adjusted beta 68.6 cells/μL, 95% CI, 3.9-133.4 cells/μL, P=0.04). We found no associations between CYP2B6 genotypes and virologic response or toxicity.

conclusionsCYP2B6 516G>T and CYP2B6 983T>C genotypes were strongly associated with plasma nevirapine concentration, which predicted immunologic response in women on nevirapine-based antiretroviral therapy. These data support continued work on the potential utility of human genetic testing to inform nevirapine dosage optimization for individual patients.

Indexed as

Antiretroviral therapyCYP2B6HIV infectionNevirapinePharmacogeneticsWomen

Identifiers

PMID25878720
PMCPMC4397818
OpenAlexW2059767880

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.