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INTEGRASE AND OTHER TRANSMITTED HIV DRUG RESISTANCE: 23 US JURISDICTIONS, 2013-2016
Robert P. McClung1, Cheryl B. Ocfemia1, Neeraja Saduvala1, Alexandra M. Oster1, Walid Heneine1, Jeffrey A. Johnson1, Angela L. Hernandez1
1CDC, Atlanta, GA, USA
Drug resistance testing based on protease (PR) and reverse transcriptase (RT) gene mutations is recommended for all patients at entry to HIV care and should include testing for integrase (IN) mutations when transmitted resistance to integrase strand transfer inhibitors (INSTIs) is a concern. HIV sequence data from drug resistance tests are reported to the U.S. National HIV Surveillance System (NHSS) as a part of routine surveillance activities. We analyzed data from 2013−2016 to understand trends in HIV sequence reporting and the prevalence of transmitted drug resistance-associated mutations (TDRMs).
For persons with HIV infection diagnosed during 2013−2016 and no evidence of prior antiretroviral therapy use, we analyzed sequences collected within 3 months of diagnosis and reported to NHSS by 12/2017. We included states in which ≥20% of HIV diagnoses during the 4-year period had an analyzable sequence and defined TDRMs using the CDC HIV-1 surveillance mutation list. We examined reporting by sequence type, prevalence of TDRMs and temporal trends for sequence types reported and TDRMs detected from 2013−2016.
The 23 states reported sequences for 36,288 (32%) of 113,121 HIV diagnoses from 2013–2016. Among persons with eligible sequences, prevalence of IN sequences obtained increased from 3.7% in 2013 to 23.0% in 2016 while prevalence of PR/RT sequences decreased from 99.2% to 93.0%. TDRMs were detected for 6,880 (19.0%) sequences, including TDRMs to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (11.9%), nucleoside reverse transcriptase inhibitors (nRTIs) (6.8%), protease inhibitors (PIs) (4.3%), and INSTIs (0.8%). INSTI TDRM prevalence did not differ by sex, age group, or race/ethnicity. Prevalence was low for TDRMs to 2 drug classes (2.4%) or ≥3 drug classes (0.3%). TDRM prevalence increased from 2013 to 2016 for NNRTIs (11.3% to 12.4%, p=0.012) and INSTIs (0.8% to 1.1%, p=0.041) but not for other drug classes.
NNRTI TDRM prevalence continues to increase, outpacing all other HIV drug classes. During this period of increasing INSTI use (and IN sequence reporting) INSTI TDRM prevalence also increased. Though drug resistance testing based on PR/RT gene sequencing is recommended for all new HIV diagnoses, an increasing proportion have only an IN sequence reported, precluding detection of TDRMs for nRTIs, which remain a critical backbone of multidrug therapy.