by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

July 13, 2021

Featured Literature:

Parienti JJ, Fournier AL, Cotte L, et al.  Forgiveness of dolutegravir-based triple therapy compared to older antiretroviral regimens: a prospective multicenter cohort of adherence patterns and HIV-RNA replication.  Open Forum Infec Dis.  2021 July 1; ofab316.  doi: 10.1093/ofid/ofab316.  

This international, multi-center prospective study aimed to assess dolutegravir adherence patterns associated with viremia.  Participants received triple therapy, and three subgroups were examined: (a) ARV-naïve PWH; (b) treatment-experienced PWH undergoing regimen modification due to virologic failure; and (c) virologically suppressed PWH undergoing regimen switch.  Participants were followed with electronic adherence monitoring; results were compared to raltegravir-, boosted PI-, or NNRTI-anchored combinations.  At 6 months, 92% of participants on dolutegravir had VL ≤50 copies/mL.  The proportion of subgroup participants with VL between 51 and 200 copies/mL were: 8% for ARV-naïve participants; 17% for participants with prior virologic failure; and 2% for the switch subgroup.  For participants with low-level viremia and successful genotype sequencing, no INSTI mutations were found.  Adherence pattern to dolutegravir-based therapy did not predict virologic suppression; this was in strong contrast to older regimens.  Further, dolutegravir use was significantly and independently associated with lower risk of viremia compared to other ARVs in participants with lower (≤95%) adherence levels.  Investigators concluded that dolutegravir-based triple therapy appears to be more forgiving [over the short-term] to missed doses, either by average adherence or treatment interruptions, compared to older ARVs.  Risk of viremia was consistent with the previously suggested >80% level of average adherence reported in other studies.

Author’s Commentary:

For various reasons, including high barrier to resistance, potency, low pill burden, and favorable tolerability and pharmacokinetic profiles, dolutegravir remains a preferred anchor agent among many HIV treatment guidelines.  This “real world” study of adherence using electronic drug monitoring devices helps characterize short-term virologic outcomes and dolutegravir’s “forgiveness” with missed doses.  Findings add to our current understanding of the durability and risk of HIV drug resistance development seen thus far with dolutegravir-based regimens and may be especially applicable for the care of PWH who may have less than high levels of medication adherence.  Further, as experience with dolutegravir-containing two-drug regimens increases, it will be important to understand whether and how varying adherence patterns with two-drug regimens affect virologic and resistance outcomes. 

The author has no conflicts of interest to disclose.

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