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

Abstract

Background: Transmitted 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.

Methods: We 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).

Results: Among 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.

Conclusions: Moderate 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.

Keywords: HIV-1; Southeastern United States; antiretroviral therapy; drug resistance; molecular epidemiology.

Figure 1.

A, Overall transmitted drug resistance (TDR) prevalence by year among 1658 antiretroviral therapy (ART)–naïve patients from 1997 to mid-2014. Fitted linear model indicated an increasing trend in the percentage of ART-naïve patients with ≥1 surveillance drug resistance mutations. B, Prevalence of TDR broken down by drug class resistance (non-nucleoside reverse transcriptase inhibitor [NNRTI], nucleoside reverse transcriptase inhibitor [NRTI], protease inhibitor [PI]). C, Increasing prevalence of NNRTI-associated TDR among 1658 ART-naïve patients despite decreasing prevalence of NNRTI-containing regimen use among UNC and Duke patients on ART. ART regimen data were abstracted starting in 2001.

Figure 2.

Twenty-five transmission clusters illustrating resistance circulation among antiretroviral therapy (ART)–naïve and ART-unknown members. Each horizontal line of dots represents 1 cluster, and each dot indicates a single patient in the cluster by date of first sequencing. All clusters have at least 3 members, all with a surveillance drug resistance mutation (SDRM) and ≥1 members with transmitted drug resistance. Clusters are ordered by drug class resistance (non-nucleoside reverse transcriptase inhibitor [NNRTI], NNRTI/nucleoside reverse transcriptase inhibitor [NRTI], NRTI, protease inhibitor) based on the SDRM shared by the majority of sequences. Within each drug class, clusters are ordered by the most recent member’s sequencing date.