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. 2023 Aug;99(5):303-310.
doi: 10.1136/sextrans-2022-055499. Epub 2022 Sep 5.

Determinants of adherence to daily PrEP measured as intracellular tenofovir diphosphate concentrations over 24 months of follow-up among men who have sex with men

Mark Am van den Elshout  1 , Elske Hoornenborg  2 , Liza Coyer  2 , Peter L Anderson  3 , Udi Davidovich  2   4 , Henry Jc de Vries  2   5 , Maria Prins  2   5 , Maarten F Schim van der Loeff  5 ; of the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative (H-TEAM)
Affiliations

Determinants of adherence to daily PrEP measured as intracellular tenofovir diphosphate concentrations over 24 months of follow-up among men who have sex with men

Mark Am van den Elshout et al. Sex Transm Infect. 2023 Aug.

Abstract

Objectives: Adherence is key to the effectiveness of oral pre-exposure prophylaxis (PrEP) to prevent HIV. Therefore, we aimed to explore factors associated with adherence to daily PrEP (dPrEP).

Methods: Men who have sex with men (MSM) using dPrEP (emtricitabine/tenofovir disoproxil) within the Amsterdam PrEP demonstration project at the Public Health Service of Amsterdam, provided dried blood spots (DBS) 12 and 24 months after PrEP initiation. From DBS, we determined intracellular tenofovir diphosphate (TFV-DP) concentrations to assess adherence; TFV-DP ≥700 fmol/punch was considered adequate. We assessed associations of sociodemographic, clinical and behavioural characteristics with TFV-DP concentrations using multivariable linear regression.

Results: Of 263 participants who attended 12-month or 24-month study visits while on dPrEP, 257 (97.7%) provided DBS at one or both visits (492 DBS in total). Median TFV-DP concentration was 1299 (IQR 1021-1627) fmol/punch (12 months: 1332 (1087-1687); 24 months: 1248 (929-1590]). Higher TFV-DP concentrations were associated with: older age (p=0.0008), condomless anal sex with a casual partner in 6 months preceding PrEP initiation (+166 fmol/punch; 95% CI 36.5 to 296) and using a mobile application providing visualised feedback on PrEP use and sexual behaviour (+146 fmol/punch; 95% CI 28.1 to 263). Lower TFV-DP concentrations were associated with longer duration of PrEP use (24 vs 12 months; -91.5 fmol/punch; 95% CI -155 to -28.1). Time-updated number of sex partners, diagnosed STIs and chemsex were not associated with TFV-DP concentrations.

Conclusions: Overall, TFV-DP concentrations were high among MSM using dPrEP, indicating excellent adherence. Especially older participants, those who reported condomless anal sex with a casual partner prior to PrEP initiation and those who used an app with visualised feedback showed higher levels of adherence. As TFV-DP concentrations had decreased slightly at 2 years of PrEP use when compared with 1 year, we emphasise the importance of adherence counselling to those who continue using PrEP.

Trial registration number: NL5413.

Keywords: HIV; cohort studies; pre-exposure prophylaxis; treatment adherence and compliance.

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Conflict of interest statement

Competing interests: The study medication was provided by Gilead Sciences based on unconditional grants. EH received advisory board fees from Gilead Sciences and speaker fees from Janssen‐Cilag, both paid to her institute. UD received unrestricted research grants and speaker’s fees from Gilead Sciences, paid to his institute. HJCdV received grants from Medigene, and advisory board and speaker fees from Gilead Sciences, Medigene, AbbVie, Janssen‐Cilag and Willpharma, paid to his institute. MP received unrestricted research grants and speaker’s fees from Gilead Sciences, Roche, AbbVie and MSD, paid to her institute. MSvdL served on an Advisory Board of MSD, paid to his institute. All other authors declared no competing interest.

Figures

Figure 1
Figure 1
Tenofovir diphosphate (TFV-DP) concentrations from dried blood spots of daily pre-exposure prophylaxis (PrEP) users in fmol/punch by study visit: 12 months and 24 months after PrEP initiation. The solid line indicates 700 fmol/punch, suggested by a previous study as the lower bound of protective drug levels. The dashed line indicates 1250 fmol/punch, corresponding to consistent adherence to daily PrEP. Box represents 25th–75th percentiles and median, whiskers upper and lower adjacent values and dots outside values. n (12 months)=246, n (24 months)=215. Amsterdam PrEP demonstration project study, Amsterdam, The Netherlands, 2016–2018.
Figure 2
Figure 2
Tenofovir diphosphate (TFV-DP) concentrations from dried blood spots of daily pre-exposure prophylaxis (PrEP) users in fmol/punch (dots) and age modelled as cubic splines (curve). The grey area represents the 95% CI around the modelled estimates. The solid line indicates 700 fmol/punch, suggested by a previous study as the lower bound of protective drug levels. The dashed line indicates 1250 fmol/punch, corresponding to consistent adherence to daily PrEP. Amsterdam PrEP demonstration project study, Amsterdam, The Netherlands, 2016–2018.
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