Statewide Longitudinal Trends in Transmitted HIV-1 Drug Resistance in Rhode Island, USA

Author:

Novitsky Vlad1,Steingrimsson Jon1,Gillani Fizza S1,Howison Mark2,Aung Su1,Solomon Matthew1,Won Cindy Y1,Brotherton Amy1,Shah Rajeev1,Dunn Casey3,Fulton John1,Bertrand Thomas4,Civitarese Anna4,Howe Katharine4,Marak Theodore4,Chan Philip14,Bandy Utpala4,Alexander-Scott Nicole4,Hogan Joseph1,Kantor Rami1

Affiliation:

1. Brown University, Providence, Rhode Island, USA

2. Research Improving People’s Life, Providence, Rhode Island, USA

3. Yale University, New Haven, Connecticut, USA

4. Rhode Island Department of Health, Providence, Rhode Island, USA

Abstract

Abstract Background HIV-1 transmitted drug resistance (TDR) remains a global challenge that can impact care, yet its comprehensive assessment is limited and heterogenous. We longitudinally characterized statewide TDR in Rhode Island. Methods Demographic and clinical data from treatment-naïve individuals were linked to protease, reverse transcriptase, and integrase sequences routinely obtained over 2004–2020. TDR extent, trends, impact on first-line regimens, and association with transmission networks were assessed using the Stanford Database, Mann-Kendall statistic, and phylogenetic tools. Results In 1123 individuals, TDR to any antiretroviral increased from 8% (2004) to 26% (2020), driven by non-nucleotide reverse transcriptase inhibitor (NNRTI; 5%–18%) and, to a lesser extent, nucleotide reverse transcriptase inhibitor (NRTI; 2%–8%) TDR. Dual- and triple-class TDR rates were low, and major integrase strand transfer inhibitor resistance was absent. Predicted intermediate to high resistance was in 77% of those with TDR, with differential suppression patterns. Among all individuals, 34% were in molecular clusters, some only with members with TDR who shared mutations. Among clustered individuals, people with TDR were more likely in small clusters. Conclusions In a unique (statewide) assessment over 2004–2020, TDR increased; this was primarily, but not solely, driven by NNRTIs, impacting antiretroviral regimens. Limited TDR to multiclass regimens and pre-exposure prophylaxis are encouraging; however, surveillance and its integration with molecular epidemiology should continue in order to potentially improve care and prevention interventions.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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