Prevalence of HIV-1 Transmitted Drug Resistance in Rhode Island From 2004 to 2020

Results of a statewide longitudinal study in Rhode Island found that the prevalence of HIV-1 transmitted drug resistance (TDR) increased between 2004 and 2020. These findings were published in Open Forum Infectious Diseases.

Investigators obtained all available data on HIV-1 sequences from patients with HIV infection who received clinical care in Rhode Island between 2004 and 2020; all patients were naïve to antiretroviral therapy (ART). Investigators collected HIV-1 protease and reverse transcriptase (PRRT) and integrase sequences from provider-ordered resistance testing performed at commercial laboratories that used Sanger sequencing. They used PRRT sequences to assess the association between TDR and molecular clusters. The TDR analyses included resistance to any class, dual-class, triple-class, class-specific, and individual surveillance drug-resistant mutation (SDRM) lists.

To assess the effect of TDR on ART, investigators used detected SDRMs to determine the prevalence of intermediate and higher predicted resistance levels to all relevant initial and subsequent ART options. They also used the Mann-Kendall statistic to quantify trends in TDR across time.

Among a total of 2674 adults diagnosed with HIV infection in 2019, 1123 (42%) had available sequencing data by the end of 2020 prior to ART initiation. Of these patients, 77% were men, 56% were aged between 25 and 44 years, 60% were White, 55% were men who have sex with men, and 58% were born in the US. In addition, the mean CD4⁺ T-cell count was 400 cells/µL, HIV-1 PRRT sequences were available for 1122 patients, and integrase sequences were available for 49 patients sampled between 2017 and 2020.

Of 1122 PRRT sequences assessed, 162 (14%) had TDR, showing a steady increase from approximately 8% in the mid-2000s to 26% in 2020 with annual fluctuations (Mann-Kendall test statistic, 0.47; 95% CI, 0.16-0.68). Although no integrase strand transfer inhibitor (INSTI) SDRMs were observed among the 49 available sequences, accessory INSTI mutations occurred among 5 patients with HIV-1 subtype B.

The median time from diagnosis to genotyping was 25 (IQR, 13-138) days for patients without SDRMs and 24 (IQR, 12-71) days for those with SDRMS (P =.54).

Stratification of individual SDRMs by ART class showed that among non-nucleotide reverse transcriptase inhibitor (NNRTI) SDRMs, K103N mutations were the most prevalent, increasing from 5% between 2004 and 2007 to 12% between 2016 and 2020.

Between 2004 and 2020, the prevalence of dual-class TDR remained less than 4%, with a slight increase over time (Mann-Kendall test statistic, 0.24; 95% CI, -0.022 to 0.46). There was no triple-class TDR observed on analysis of data captured after 2010. In patients (n=17) with dual- and triple-class TDR, 82% and 76% had NRTI and NNRTI SDRMs, respectively. Predicted resistance SDRM profiles and their dynamics over time mimicked individual mutation patterns, with high and increasing predicted resistance to NNRTIs and low and increasing resistance to NRTIs.

Of the 17 patients with dual- and triple-class TDR, 12 responded rapidly to their first-line regimen and 5 had delayed responses to their first-line regimens and/or subsequently failed treatment.

Among 376 patients, there were a total of 123 clusters identified, of which 91 (74%) included only those without TDR, 15 (12%) included those with and without TDR, and 17 (14%) included only those with TDR. pa the In addition, the proportion of patients with SDRMs was similar among those who were clustered vs unclustered (P =.56), and those in smaller clusters were more likely to have TDR (P =.025).

Study limitations were the inability to determine the prevalence of TDR among undiagnosed and unsampled patients, the potential inclusion of patients with undocumented use of ART, and that full treatment histories were limited.

According to the investigators, “these data suggest at least some [HIV-1] transmission with SDRMs within networks and support routine local and statewide TDR surveillance.” They concluded that “integrating TDR surveillance with real-time molecular epidemiology approaches…would allow statewide and regional analyses toward HIV and TDR prevention.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference

Novitsky V, Steingrimsson J, Gillani FS, et al. Statewide longitudinal trends in transmitted HIV-1 drug resistance in Rhode Island, USA. Open Forum Infect Dis. Published online December 7, 2021. doi:10.1093/ofid/ofab587