Background:
Kenya began rolling out DTG-based ART in late 2017 as both 1st- and 2nd-line treatment for adults and children living with HIV (PLHV). HIV drug resistance (HIVDR) data is limited in PLHIV failing DTG-based ART. We used the cyclical-acquired HIVDR (CADRE) methodology to assess the frequency of HIVDR mutations in PLHIV with detectable viremia on DTG-based ART between January and March 2023 in Kenya.
Methods:
The National AIDS and STI control program(NASCOP) collected remnant plasma from HIV viral load testing between January and March 2023 from PLHIV in 15 high/moderate HIV prevalence counties receiving DTG-based ART through the Kenya HIV Care and Treatment Program. We received 191 samples from PLHIV out of the expected CADRE-calculated sample size of 622. Plasma was genotyped using Thermo-Fisher Sanger pro/RT/int sequencing on samples >200 cp/mL and mutations were identified using Stanford HIVdb v9.5. Clinical and demographic data on treatment history and duration was obtained from viral load request forms.
Results:
Samples were available for 138 of 332 (42%) adults, median age 36 [IQR 26-45] years, and 52 of 290 (18%) children (median age 15 [IQR 12-16] years) with 1 of unknown age. 146 of 191 total (76%) received DTG as 2nd-line, with 141 on NNRTI-based ART and 5 on PI-based ART for a median of 5 [IQR 2-8] years before switching to DTG-based ART; the remaining PLHIV (45 of 191; 24%) received DTG as 1st-line. 56 of 191 (29%) had HIV-1 VL >200 cp/mL; 44 of 56 (79%) were successfully genotyped. 7 of 32 (22%) ART-experienced PLHIV had INSTI resistance with E138K alone or with up to three additional major INSTI mutations including T66I, G118R, G140A, S147G, Q148KNR, and/or N155H. All 7 also had multiple NNRTI and NRTI DRMs including 5 with thymidine analogue mutations. 1 of 12 (8%) PLHIV on 1st-line TLD had VL 296 c/mL after 17 months on ART and the INSTI DRM R263K with only K70Q and M184V in RT (Table).
Conclusions:
The frequency of INSTI HIVDR was high (22%) in ART-experienced PLHIV on DTG-based ART used as 2nd-line ART and lower (8%) in ART-naïve adults using DTG for 1st-line ART, suggesting the risk of failing DTG may be higher in a background of pre-existing mutations to NRTIs in the regimen. Our data emphasizes the importance of HIVDR monitoring in PLHIV on DTG-based ART given the anticipated introduction of long-acting cabotegravir for HIV prevention and the potential for transmission of INSTI-resistant virus from those on failing DTG-based ART to cabotegravir PrEP recipients.
