Sensitive sentinel mutation screening reveals differential underestimation of transmitted HIV drug resistance among demographic groups

Jin-fen Li, Laurie Linley, Richard Kline, Rebecca Ziebell, Walid Heneine, Jeffrey A. Johnson

To examine the association of majority- and minority-level transmitted HIV drug resistance (TDR) among diverse demographic populations in the United States and assess what different mutations may infer about TDR risk and engagement in care. Used sensitive assays to screen 1070 de-identified convenience plasma specimens from United States national HIV surveillance conducted in 2009-2011 on newly diagnosed persons with no evidence of antiretroviral drug use. We applied validated allele-specific PCR for five HIV reverse transcriptase mutations as sentinel markers of TDR. The total and minority-level prevalence of TDR by demographic characteristics was compared. Sensitive screening identified 72% more TDR than conventional sequencing for the five mutations assessed (13.6% vs. 7.9%, p < 0.0001), with K65R having the greatest increase (0% to 1.7%). One-third of K65R was in persons who also had ≥1 of the other mutations screened. The total TDR prevalence among whites (16.4%) and blacks (14.9%) was significantly higher than that among Hispanics/Latinos (6.4%) (p = 0.005 and 0.013, respectively). TDR prevalence was highest (23.1%) in those 13-19 years (85% black). TDR prevalence among females (72% black) was nearly as high as among MSM (47% black) (14.3% vs 15.1%, respectively). A significant proportion of TDR, primarily in older, white MSM, was undetected by conventional testing. The greatest underestimation was for rapid-decaying mutations typically associated with the source virus having recent exposure to ART. However, total TDR prevalence was highest in the <20 year age group who were predominantly black, underscoring the importance of prevention efforts for at-risk youth.