Increasing Prevalence of HIV-1 Transmitted Drug Resistance in Portugal: Implications for First Line Treatment Recommendations

Abstract

Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR).

Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017.

Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression.

Results and discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001).

Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.

Keywords: HIV-1; Portugal; acquired drug resistance; transmitted drug resistance.

Figure 1

Proportion of (A) transmitted drug resistance (TDR) in sequences from ART-NP between 2003 and 2017 and (B) of acquired drug resistance (ADR) in ART-EP between 2001 and 2017. NRTI, nucleotide reverse transcriptase inhibitors; NNRTI, non-nucleotide reverse transcriptase inhibitors; PI, protease inhibitors; ART-NP, antiretroviral-naïve patients; ART-EP, antiretroviral-experienced patients.

Figure 2

Proportion of resistance mutations in sequences (A) ART-NP and (B) ART-EP and proportion of M184V, K103N and L90M mutations in (C) ART-NP and (D) ART-EP over time between 2001 and 2017. TAM, Thymidine analog mutation; NRTI, nucleotide reverse transcriptase inhibitors; NNRTI, non-nucleotide reverse transcriptase inhibitors; PI, protease inhibitors. ART-NP, antiretroviral-naïve patients; ART-EP, antiretroviral-experienced patients.

Figure 3

Predicted phenotypic resistance (Stanford scores) for antiretroviral drugs currently recommended as first line therapy in Portugal (A) for ART-NP (2003–2017) and (B) for ART-EP (2003–2017). Scores of low-level (score 2 and 3), intermediate level (score 4) or high-level (score 5) resistance were used to predict phenotypic resistance. Abbreviations: NRTI, nucleoside reverse transcriptase inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitors; PI, protease inhibitors; FTC, emtricitabine; TDF, tenofovir; 3TC, lamivudine; ABC, abacavir; EFV, efavirenz; RPV, rilpivirine; DRV/r, darunavir; LPV/r, lopinavir; ATV/r, atazanavir; ART-NP, antiretroviral-naïve patients; ART-EP, antiretroviral-experienced patients.