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Major and Minor PI Mutations in MONET Darunavir Monotherapy Trial
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
This latest resistance update on people taking darunavir/ritonavir monotherapy or darunavir/ritonavir plus two nucleosides in the randomized MONET trial describes only one major protease inhibitor (PI) mutation in either arm and no concerning patterns in minor PI mutations [1].
MONET randomized 256 people with a viral load consistently below 50 copies and no history of virologic failure or PI resistance to darunavir/ritonavir with two nucleosides or to darunavir/ritonavir monotherapy [2]. The 48-week analysis demonstrated that monotherapy is virologically noninferior to continued triple therapy.
To date only one major PI mutation (defined by the IAS-USA list) has emerged in each study arm. One monotherapy patient had a viremic blip to 63 copies at study week 12 and emergence of the L33F darunavir-associated resistance mutation. Viral load fell back below 50 copies at the next measurement and has remained there through 96 weeks of follow-up. This person's virus remained fully sensitive to darunavir. No nucleoside mutations emerged in this person, and no major PI mutations or nucleoside mutations emerged in 26 other successfully genotyped people in the monotherapy arm.
Fourteen monotherapy patients had two or more sequential genotypes during sustained viremia, a median of 2 to 5 months apart. Each genotype detected a median of 3 minor IAS-USA mutations (range 0 to 5). Over time, the number or type of minor IAS-USA mutations did not change in 10 of these 14 people. In three people, one or more minor IAS-USA mutations disappeared over time, and in one person minor mutations disappeared and were replaced by others. Minor PI mutations did not differ between the monotherapy arm and the triple-therapy arm, except for the I93L/M mutation, which was significantly more frequent in the monotherapy arm (P = 0.01).
The investigators compared prevalence of each minor IAS-USA mutation with prevalence among PI-naive people in the Stanford resistance database. Prevalence of minor mutations at five protease positions was significantly more common in monotherapy-treated people than in the Stanford database: K20I/R/M/T/V, L33I/V, L63P, H69K, and I93L/M (P < 0.01). Minor PI mutations at two positions were more frequent in the triple-therapy arm than in the Stanford database: K20I/R/M/T/V and Q58E (P < 0.01).
References
1. Pulido F, Arribas JR, Hill A, van Delft Y, Moecklinghoff C. Analysis of major and minor IAS-USA PI mutations in the MONET trial of darunavir/ritonavir monotherapy versus DRV/r + 2 NRTIs. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract P131.
2. Arribas JR, Horban A, Gerstoft J, et al. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010;24:223-230.
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