Transmitted Drug Resistance Among Human Immunodeficiency Virus (HIV)-1 Diagnoses in the United States, 2014–2018

Abstract

Background Transmitted HIV drug resistance can threaten the efficacy of antiretroviral therapy (ART) and preexposure prophylaxis (PrEP). Drug resistance testing is recommended at entry to HIV care in the United States and provides valuable insight for clinical decision-making and population-level monitoring. Methods We assessed transmitted drug resistance-associated mutation (TDRM) prevalence and predicted susceptibility to common HIV drugs among U.S. persons with HIV diagnosed during 2014–2018 who had a drug resistance test performed ≤3 months after HIV diagnosis and reported to the National HIV Surveillance System and who resided in 28 jurisdictions where ≥20% of HIV diagnoses had an eligible sequence during this period. Results Of 50,747 persons in the analysis, 9,616 (18.9%) had ≥1 TDRM. TDRM prevalence was 0.8% for integrase strand transfer inhibitors (INSTI), 4.2% for protease inhibitors, 6.9% for nucleoside reverse transcriptase inhibitors, and 12.0% for non-nucleoside reverse transcriptase inhibitors. Most individual mutations had a prevalence <1.0% including M184V (0.9%) and K65R (0.1%); K103N was most prevalent (8.6%). TDRM prevalence did not increase or decrease significantly during 2014–2018 overall, for individual drug classes, or for key individual mutations except for M184V (12.9% increase per year, 95% CI=5.6–20.6). Conclusions TDRM prevalence overall and for individual drug classes remained stable during 2014–2018; transmitted INSTI resistance was uncommon. Continued population-level monitoring of INSTI and NRTI mutations, especially M184V and K65R, is warranted amidst expanding use of second-generation INSTI and PrEP.

Changing Proportions of HIV-1 Subtypes and Transmitted Drug Resistance Among Newly Diagnosed HIV/AIDS Individuals — China, 2015 and 2018

“…A study that included TDR prevalence data from 2001 to 2017 in China estimated that TDR prevalence was 4.1% ( 9 ), which is consistent with the results of this study. Reports on drug resistance testing from the WHO revealed that between 2014 and 2019, the median rate of transmission-resistant drugs was 4.1% in Southeast Asia, 6.0% in Sub-Saharan Africa, 9.1% in Latin America, 8.5% in Europe, and 14.2% in North America ( 10 ). Conversely, the prevalence of TDR was much higher in Europe and North America, which was consistent with the longer existence and variety of antiviral treatment.…”

“…Molecular monitoring results of newly diagnosed individuals in China showed that the most common mutations in patients’ resistance to NNRTI were E138G and V179E ( 12 ). Moreover, E138K was found to be the most common mutation in HIV-1 patients resistant to NNRTI in the US, according to an analysis of TDR from 2014 to 2018 ( 10 ). The impact of the combination of E138 and V179 on both NNRTI susceptibility and virologic outcome in patients deserves investigation.…”

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence

“…). The proportion of countries meeting the target of having at least 5% of patients on secondline ART increased from 45% (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) in 2017 to 56% (14 of 25) in 2020. Overall, most countries reported sub-optimal performance in preventing HIVDR, indicating the need to strengthen the quality and monitoring systems and implement sustainable solutions.…”

Impact of HIV-1 Resistance-Associated Mutations on Susceptibility to Doravirine: Analysis of Real-World Clinical Isolates

“…Within this population from the United States (US), TDR was more commonly attributable to nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) ( 9 ). A more recent study conducted in PLWH in the US from 2014 to 2018 estimated that the prevalence of NNRTI mutations was 12% ( 10 ). Studies have documented a progressive increase in the prevalence of TDR across several geographic regions ( 9 – 12 ).…”

“…A more recent study conducted in PLWH in the US from 2014 to 2018 estimated that the prevalence of NNRTI mutations was 12% ( 10 ). Studies have documented a progressive increase in the prevalence of TDR across several geographic regions ( 9 – 12 ). Moreover, changing practices in ART may contribute additional mutations to TDR, particularly for NNRTIs ( 13 ).…”