Dolutegravir resistance is rare, but some risk factors can up the odds

[Jim Allen]

Interesting read, although not surprising results.*

Aidsmap in article in full: https://www.aidsmap.com/news/dec-2023/dolutegravir-resistance-rare-some-risk-factors-can-odds

In Short:

No drug is immune to resistance, but dolutegravir, one of the most widely used HIV drugs, has so far shown an excellent barrier to resistance. Nevertheless, a large study that analysed data from several countries found that resistance was more common in people who took dolutegravir monotherapy or dual therapy with lamivudine, or who had resistance to NRTIs (the backbone drugs usually combined with dolutegravir).

In clinical and real-world studies, treatment failure on dolutegravir-based regimens is seen usually in fewer than 5% of participants. Even in case of treatment failure, very few people develop resistance to the drug which is why it is said to have a high barrier to resistance.

Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on 599 people who had detectable viral load on dolutegravir-based therapy and had resistance testing.  (540 of the ‘participants’ were included in the analysis)

Fourteen per cent of all participants had at least one integrase inhibitor resistance mutation and 3% had more than one. It is important to note that the presence of a resistance mutation does not directly translate into treatment failure, hence some mutations may be present without affecting viral suppression.

Monotherapy
Of all risk factors, being on dolutegravir monotherapy rather than triple therapy had the strongest association with dolutegravir resistance. While it is not surprising that monotherapy contributed to increased resistance, it is certainly surprising that there were 18 people on monotherapy as none of the existing HIV treatment guidelines supports its use.

Dual therapy
Dolutegravir-based dual therapy was also associated with an increased risk of dolutegravir resistance; particularly dual therapies comprising dolutegravir plus lamivudine (available as Dovato). Other dolutegravir dual therapies had a weaker association with resistance.

Despite other data giving reassurance about the efficacy of dolutegravir-based dual therapies, these findings warn that dual therapy, particularly with lamivudine, may still come with some level of increased risk of resistance.

Loosli T. et al. HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis. The Lancet HIV 10: e733-e741, 2023.

DOI: https://doi.org/10.1016/S2352-3018(23)00228-X

*

DOLUMONO failed DTG monotherapy
https://forums.poz.com/index.php?topic=66233.0

MONCAY failed DTG monotherapy
https://forums.poz.com/index.php?topic=70588.msg

https://i-base.info/htb/31289

Swiss cohort - Monotherapy success (Primary infection)
https://forums.poz.com/index.php?topic=77185.msg

[leatherman]

it is certainly surprising that there were 18 people on monotherapy as none of the existing HIV treatment guidelines supports its use.

monotherapy?!? Isn't that the very antithesis of what we know about HAART?

Without looking at the actual study, I notice this article doesn't even mention the biggest issue with resistance happening in the first place - non-compliance with daily treatment. That's not a fault of the drug; but of the patient. Neither is monotherapy is not the fault of the drug; but of the prescribing doctor.

[Jim Allen]

. Neither is monotherapy is not the fault of the drug; but of the prescribing doctor.

Yeah. Given the odds known of a shitty outcome down the line, it's concerning to see DTG monotherapy being prescribed.