Evidence map›Paper›PMID 28827836›Full record

ArticlePloS one2017

Sub-therapeutic nevirapine concentration during antiretroviral treatment initiation among children living with HIV: Implications for therapeutic drug monitoring.

Bindu Parachalil Gopalan, Kayur Mehta, Reena R D'souza, Niharika Rajnala, Hemanth Kumar A K, Geetha Ramachandran, Anita Shet

Abstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
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

7 authors.

Bindu Parachalil GopalanDivision of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, Karnataka, India.
Kayur MehtaDepartment of Pediatrics, St. John's Medical College Hospital, Bangalore, Karnataka, India.
Reena R D'souzaDivision of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, Karnataka, India.
Niharika RajnalaDivision of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, Karnataka, India.
Hemanth Kumar A KNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, Tamil Nadu, India.
Geetha RamachandranNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, Tamil Nadu, India.
Anita ShetDivision of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, Karnataka, India.ORCID http://orcid.org/0000-0002-7204-8164

Funding

DBT-Wellcome Trust India Alliance IA/S/13/2/501017Wellcome Trust
6 · The paper itself

Abstract

Nevirapine, a component of antiretroviral therapy (ART) in resource-limited settings, known for auto-induction of metabolism, is initiated at half therapeutic dose until day 14 ('lead-in period'), and subsequently escalated to full dose. However, studies have shown that this dosing strategy based on adult studies may not be appropriate in children, given that younger children have higher drug clearance rates. In this prospective cohort study, we studied trough plasma nevirapine levels by high performance liquid chromatography (HPLC) at days 7, 14 (lead-in period) and 28 (full dose period) after ART initiation amongst HIV-1 infected children initiating nevirapine-based ART in southern India. Among the 20 children (50% male, median age 9 years) included in the study, sub-therapeutic trough plasma nevirapine concentration (<4μg/ml) was seen in 65% (13/20) of children during the lead-in period within two weeks of ART initiation and among 10% of children at 4 weeks during full-dose nevirapine. Adherence was documented as ≥95% in all children by both caregiver self-report and pill count. Median nevirapine concentrations achieved at week 1 was 4.8 μg/ml, significantly lower than 8 μg/ml, the concentration achieved at week 4 (p = 0.034). Virological failure at one year of ART was observed in six children, and was not associated with median nevirapine concentration achieved during week 1, 2 or 4. We conclude that the dose escalation strategy currently practiced among young children living with HIV-1 resulted in significant subtherapeutic nevirapine concentration (≤4μg/ml) during the lead-in period. We call for a closer look at pediatric-focused dosing strategies for nevirapine initiation in young children. Further studies to establish age-appropriate threshold nevirapine concentration are warranted in young children to corroborate the role of therapeutic drug monitoring in predicting virological outcome.

Indexed as

Drug MonitoringChildChromatography, High Pressure LiquidDose-Response Relationship, DrugFemaleHIV InfectionsHumansMaleNevirapinePatient ComplianceProspective StudiesReverse Transcriptase InhibitorsViral LoadNevirapineReverse Transcriptase Inhibitors

Identifiers

PMID28827836
PMCPMC5565187

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.