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Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir based antiretroviral therapy

Abstract:

Objective: We aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia.

Design: Cross-sectional study among people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART).

Methods: We used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia ≥ 1000 copies/mL using logistic regression models. In exploratory analyses, we used receiver operating curves to estimate optimal urine TFV and DBS TFV-DP thresholds to predict concurrent viraemia.

Results: Among 124 participants, 68 (54.8%) were women, median age was 39 years (interquartile range [IQR] 34-45) and 74 (59.7%) were receiving efavirenz versus 50 (40.3%) receiving dolutegravir. Higher concentrations of urine TFV (1000 ng/mL increase, odds ratio [OR] 0.97 95%CI 0.94-0.99, p=0.005) and DBS TFV-DP (100 fmol/punch increase, OR 0.76, 95%CI 0.67-0.86, p<0.001) were associated with lower odds of viraemia. There was evidence that these associations were stronger among people receiving dolutegravir than among people receiving efavirenz (urine TFV p=0.072, DBS TFV-DP p=0.003). Nagelkerke Pseudo-R2 for the DBS TFV-DP models was higher than for the urine TFV models, demonstrating a stronger relationship between DBS TFV-DP and viraemia. Among people receiving dolutegravir, a DBS TFV-DP concentration of 483 fmol/punch had 88% sensitivity and 85% specificity to predict concurrent viraemia ≥ 1000 copies/ml.

Conclusions: Among PWH receiving TDF-based ART, urine TFV concentrations, and in particular DBS TFV-DP concentrations, were strongly associated with concurrent viraemia, especially among people receiving dolutegravir.

Publication status:
Published

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Preprint server copy:
10.1101/2023.09.27.23296217

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
Primary Care Health Sciences
Oxford college:
Green Templeton College
Role:
Author
ORCID:
0000-0001-6072-1430


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Funder identifier:
https://ror.org/029chgv08
Grant:
216421/Z/19/Z
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Funder identifier:
https://ror.org/0187kwz08
Grant:
NF-SI-0515-10056
CL-2022-13-005
MIC-2016-018
NIHR300105
More from this funder
Funder identifier:
https://ror.org/02wxr8x18


Preprint server:
medRxiv
Publication date:
2023-09-28
DOI:
Server owner:
Cold Spring Harbor Laboratory


Language:
English
Keywords:
Pubs id:
1557612
Local pid:
pubs:1557612
Deposit date:
2026-05-29
ARK identifier:

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