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. 2022 Apr 13:13:846943.
doi: 10.3389/fmicb.2022.846943. eCollection 2022.

Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters

Mafalda N S Miranda  1 , Marta Pingarilho  1 , Victor Pimentel  1 , Maria do Rosário O Martins  1 , Rolf Kaiser  2 , Carole Seguin-Devaux  3 , Roger Paredes  4 , Maurizio Zazzi  5 , Francesca Incardona  6   7 , Ana B Abecasis  1
Affiliations

Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters

Mafalda N S Miranda et al. Front Microbiol. .

Abstract

Background: The increased use of antiretroviral therapy (ART) has decreased mortality and morbidity of HIV-1 infected people but increasing levels of HIV drug resistance threatens the success of ART regimens. Conversely, late presentation can impact treatment outcomes, health costs, and potential transmission of HIV.

Objective: To describe the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in HIV-1 infected patients followed in Europe, to compare its patterns in late presenters (LP) vs non-late presenters (NLP), and to analyze the most prevalent drug resistance mutations among HIV-1 subtypes.

Methods: Our study included clinical, socio-demographic, and genotypic information from 26,973 HIV-1 infected patients from the EuResist Integrated Database (EIDB) between 1981 and 2019.

Results: Among the 26,973 HIV-1 infected patients in the analysis, 11,581 (42.9%) were ART-naïve patients and 15,392 (57.1%) were ART-experienced. The median age was 37 (IQR: 27.0-45.0) years old and 72.6% were males. The main transmission route was through heterosexual contact (34.9%) and 81.7% of patients originated from Western Europe. 71.9% of patients were infected by subtype B and 54.8% of patients were classified as LP. The overall prevalence of TDR was 12.8% and presented an overall decreasing trend (p for trend < 0.001), the ADR prevalence was 68.5% also with a decreasing trend (p for trend < 0.001). For LP and NLP, the TDR prevalence was 12.3 and 12.6%, respectively, while for ADR, 69.9 and 68.2%, respectively. The most prevalent TDR drug resistance mutations, in both LP and NLP, were K103N/S, T215rev, T215FY, M184I/V, M41I/L, M46I/L, and L90M.

Conclusion: Our study showed that the overall TDR (12.8%) and ADR (68.5%) presented decreasing trends during the study time period. For LP, the overall TDR was slightly lower than for NLP (12.3 vs 12.6%, respectively); while this pattern was opposite for ADR (LP slightly higher than NLP). We suggest that these differences, in the case of TDR, can be related to the dynamics of fixation of drug resistance mutations; and in the case of ADR with the more frequent therapeutic failure in LPs.

Keywords: HIV-1 infection; acquired drug resistance; late presenters; non-late presenters; transmitted drug resistance.

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Conflict of interest statement

FI was employed by IPRO—InformaPRO S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Gilead Sciences. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

Figures

FIGURE 1
FIGURE 1
Proportion of (A) overall transmitted drug resistance (TDR), (B) of protease inhibitors (PIs), (C) of nucleoside reverse transcriptase inhibitor (NRTIs) and (D) of non-nucleoside reverse transcriptase inhibitor (NNRTIs) in sequences from drug-naïve patients between three periods 1995–2002, 2003–2010, and 2011–2019. OR, Odds Ratio; p, p-value.
FIGURE 2
FIGURE 2
Proportion of (A) overall acquired drug resistance (ADR), (B) of protease inhibitors (PIs), (C) of nucleoside reverse transcriptase inhibitor (NRTIs) and (D) of non-nucleoside reverse transcriptase inhibitor (NNRTIs) in sequences from drug-experienced patients between three periods 1995–2002, 2003–2010 and 2011–2019. OR, Odds Ratio; p, p-value.
FIGURE 3
FIGURE 3
Proportion of transmitted and acquired drug resistance per country of follow-up in two different time periods. (A) Between 2008 and 2012; (B) between 2013 and 2018. TDR, Transmitted drug resistance; ADR, Acquired drug resistance; IT, Italy; DE, Germany; LU, Luxembourg; PT, Portugal.
FIGURE 4
FIGURE 4
ART-naïve mutations in Non-Late-Presenters (NLP) vs Late Presenters (LP). PIs, protease inhibitors; NRTIs, nucleoside reverse transcriptase inhibitor; NNRTIs, non-nucleoside reverse transcriptase inhibitor.
FIGURE 5
FIGURE 5
ART-experienced mutations in Non-Late-Presenters (NLP) vs Late Presenters (LP). PIs, protease inhibitors; NRTIs, nucleoside reverse transcriptase inhibitor; NNRTIs, non-nucleoside reverse transcriptase inhibitor.
FIGURE 6
FIGURE 6
Mutations in Non-Late presenters (NLP) and Late presenters (LP) in subtype B (A) and subtype non-B (B) for ART-naïve patients. PIs, protease inhibitors; NRTIs, nucleoside reverse transcriptase inhibitor; NNRTIs, non-nucleoside reverse transcriptase inhibitor.
FIGURE 7
FIGURE 7
Mutations in Non-Late presenters (NLP) and Late presenters (LP) in subtype B (A) and subtype non-B (B) for ART-experienced patients. PIs, protease inhibitors; NRTIs, nucleoside reverse transcriptase inhibitor; NNRTIs, non-nucleoside reverse transcriptase inhibitor.
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