Transmitted HIV Drug Resistance Is High and Longstanding in Metropolitan Washington, DC

Abstract

Background: Washington, DC, has 2.5% human immunodeficiency virus (HIV) prevalence, 3.9% among African Americans. Antiretrovirals (ARTs) are the cornerstone for treatment and prevention. Monitoring changes in transmitted drug resistance (TDR) is critical for effective HIV care.

Methods: HIV genotype data for individuals enrolled in research studies in metropolitan Washington, D.C., were used to identify TDR using the World Health Organization mutation list [Bennett DE, Camacho RJ, Otelea D, et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PloS One 2009; 4:e4724]. HIV phylogenies were reconstructed using maximum likelihood and Bayesian methods. HIV transmission clusters were supported by 1000 bootstrap values >0.70 and posterior probability >0.95 of having a common ancestor.

Results: Among 710 individuals enrolled in 1994-2013, the median age was 38.6 years, 46.2% were female, and 53.3% were African-American. TDR was 22.5% among 566 treatment-naive individuals; 15.8% had nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance, 9.8% had nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance, and 4.2% had protease inhibitor (PI) resistance. Single class TDR was 10.0%, 5.1%, and 1.6% to NRTIs, NNRTIs, and PIs. Dual TDR to PI and NRTI was seen in 1.6%, NRTI and NNRTI in 3.4%, and triple class TDR in 0.9%. TDR frequency decreased from 1994-2006 (27.1%) to 2007-2013 (19.4%; P = .02). Only 6/79 (7.6%) individuals within transmission clusters had evidence of TDR.

Discussions: We identified high prevalence of TDR among HIV-infected individuals in metropolitan Washington, DC, regardless of gender. Active surveillance for TDR is needed to guide ART usage and analyses of risk group contributions to HIV transmission and resistance.

Keywords: HIV; HIV clusters; transmission dynamics; transmitted drug resistance; women.

Figure 1.

Time trends in the frequency of transmitted drug resistance–associated mutations, 1994–2013. Point estimates for each time period are shown with 95% confidence intervals.

Figure 2.

Frequency of transmitted drug resistance (TDR) across 3 time periods: (A) Overall frequency of TDR by drug class. (B) Frequency of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)–associated TDR over time. (C) Frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI)–associated TDR over time. (D) Frequency of protease inhibitor (PI)–associated TDR over time. *T215Y includes the following revertants: L215Y/F/D/S.

Figure 3.

Bayesian phylogenetic tree of 559 subtype B human immunodeficiency virus type 1 (HIV-1) sequences. Bayesian evolutionary analysis sampling trees [31] analysis was performed with the following specifications: HKY + G + I model, uncorrelated log-normal relaxed molecular clock, tree coalescent GMRF Bayesian Skyride, and run of 2 000 000 000 states to obtain an effective sample size of 203.6. FigTree [32] was used to plot the summary Bayesian phylogenetic tree and demonstrates the star-like phylogeny of subtype B HIV-1 sequences. Nodal support of 95% or greater was required to verify transmission clusters, and these are indicated with red lines and circles. These clusters consist of 2 to 3 individuals.