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

Abstract

Objective: 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. Design: Used sensitive assays to screen 1070 deidentified convenience plasma specimens from United States national HIV surveillance conducted in 2009-2011 on newly diagnosed persons with no evidence of antiretroviral drug use. Methods: 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. Results: 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 (0-1.7%). One-third of K65R was in persons who also had at least one 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%) (P0.005 and 0.013, respectively). TDR prevalence was highest (23.1%) in those 13-19 years (85% black). TDR prevalence among women (72% black) was nearly as high as among MSM (47% black) (14.3 vs. 15.1%, respectively). Conclusion: 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 antiretroviral therapy. However, total TDR prevalence was highest in the less than 20-year age group who were predominantly black, underscoring the importance of prevention efforts for at-risk youth.