Background
Data are limited on effectiveness of dolutegravir (DTG)-based regimens among people living with HIV who inject drugs (PWID) in sub-Saharan Africa. We longitudinally studied PWID in Kenya taking DTG and assessed viral non-suppression and drug resistance.
Methods
Kenyan PWID on DTG for >6 months were enrolled, and plasma HIV RNA viral load (VL) was measured every 6 months for 2 years (May 2021-September 2023). Non-parametric survival estimations of interval-censored data assessed covariates associated with time to non-suppression (VL>200 cp/ml) considering left and right-censored observations. Viremic plasma RNA was genotyped for resistance, including minority variants, using a lab-developed PacBio sequencing assay and was assessed using the Stanford HIV Database.
Results
Among 250 enrolled participants, 125 were on methadone, 70% were male and median age was 39. Four follow-up visits were completed by 194 (77%) participants over 2 years. Of those with complete follow-up, 118 (61%) were virally suppressed at all visits, 71 (37%) experienced intermittent suppression, including 32 who were left censored (non-virally suppressed at enrollment), and 5 (3%) were always not suppressed. The odds of non-suppression for those on methadone versus not on methadone were 0.53 (p<0.05), for those living in improvised shelter/in the open versus those living at home/with a relative were 2.72 (p <0.01) and were reduced by 6% (p <0.001) per year of increased age.
Genotyping of viremic samples was successful for 93/94 (99%). Resistance to NNRTIs was common (~30-45% at each visit), but major resistance to drugs in their DTG-based regimens was relatively infrequent, with resistance to tenofovir in 4/93 (4%), lamivudine in 7/93 (8%) and major DTG resistance in 2/93 (2%) participants only observed as minority variants – S153F and Q148K detected at 1% each. DTG-mutations classified as “accessory resistance mutations” were observed at higher frequency in 34/93 (37%), including T97A (n=7), E138K (n=7), and L74M (n=6).
Conclusions
This longitudinal study among PWID living with HIV in Kenya shows that more than 1 in 3 participants on DTG-containing regimens had viral non-suppression at least intermittently. Still, resistance to DTG-containing therapy was rare across two years of follow-up. Identifying ways to mitigate barriers that may hinder viral suppression among the marginalized population will help ensure adherence to HIV care and treatment.