Prevalence and Transmission Dynamics of HIV-1 Transmitted Drug Resistance in a Southeastern Cohort

Abstract

BackgroundTransmitted drug resistance (TDR) compromises clinical management and outcomes. Transmitted drug resistance surveillance and identification of growing transmission clusters are needed in the Southeast, the epicenter of the US HIV epidemic. Our study investigated prevalence and transmission dynamics in North Carolina.MethodsWe analyzed surveillance drug resistance mutations (SDRMs) using partial pol sequences from patients presenting to 2 large HIV outpatient clinics from 1997 to 2014. Transmitted drug resistance prevalence was defined as ≥1 SDRMs among antiretroviral therapy (ART)–naïve patients. Binomial regression was used to characterize prevalence by calendar year, drug class, and demographic and clinical factors. We assessed the transmission networks of patients with TDR with maximum likelihood trees and Bayesian methods including background pol sequences (n = 15 246).ResultsAmong 1658 patients with pretherapy resistance testing, ≥1 SDRMs was identified in 199 patients, with an aggregate TDR prevalence of 12% (95% confidence interval, 10% to 14%) increasing over time (P = .02). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 8%) was common, followed by nucleoside reverse transcriptase inhibitors (4%) and protease inhibitors (2%). Factors associated with TDR were being a man reporting sex with men, white race, young age, higher CD4 cell count, and being a member of a transmission cluster. Transmitted drug resistance was identified in 106 clusters ranging from 2 to 26 members. Cluster resistance was primarily NNRTI and dominated by ART-naïve patients or those with unknown ART initiation.ConclusionsModerate TDR prevalence persists in North Carolina, predominantly driven by NNRTI resistance. Most TDR cases were identified in transmission clusters, signifying multiple local transmission networks and TDR circulation among ART-naïve persons. Transmitted drug resistance surveillance can detect transmission networks and identify patients for enhanced services to promote early treatment.

Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County

“…The low prevalence of PI TDR and the predominance of L90M among PI TDRMs is consistent with other US-based studies [7, 22, 28]. The low prevalence of PI TDR is likely attributable to the high genetic barrier of PIs [37, 38].…”

Genetic transmission networks of HIV-1 CRF07_BC strain among HIV-1 infections with virologic failure of ART in a minority area of China: a population-based study

“…Further, follow-up medical records are warranted to include more epidemiological information. Third, the phylogenetic analysis is limited by the impossibility of inferring the direction of transmission, and genetic linkage could not reflect direct transmission due to lack of behavioural information of participants [34]. Fourth, since we did not include the sequences of all PLWH for analysis, we could not draw a whole transmission network, which limited the representation of the PLWH in this area.…”

Clinical Impact and Cost-effectiveness of Genotype Testing at Human Immunodeficiency Virus Diagnosis in the United States

“…This choice may not be critical, as limited data suggest that regimens that include an NRTI pair and a later-generation INSTI, such as dolutegravir (DTG) or bictegravir (BIC), remain effective in the setting of most transmitted NRTI-R mutations [10][11][12]. The activity of DTG or BIC plus NRTIs is uncertain in the setting of high-level NRTI-R (ie, both K65R and M184V/I), but these mutations are rarely transmitted in the United States [13][14][15][16].…”

“…Under these circumstances, individuals are frequently virologically suppressed, so a genotype prior to regimen switch is infeasible. For these individuals, NNRTI-or PI-based regimens might not suppress transmitted NRTI-, NNRTI-, or PI-resistant virus [16,17].…”