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Low Failure Rate With Switch to Integrase
Inhibitor STR Despite Archived Mutations
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9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris
Mark Mascolini
Switching from a suppressive regimen to an elvitegravir or dolutegravir single-tablet regimen (STR) almost always preserved virologic control despite archived resistance mutations in a two-center French study [1]. Only 1 of 75 switchers (1.3%) had virologic failure. Almost everyone with one or more reverse transcriptase mutations had M184V, which confers resistance to lamivudine (3TC) and emtricitabine (FTC).
This retrospective analysis involved two patient groups in Rennes and Saint-Malo who traded a suppressive regimen for an STR including elvitegravir or dolutegravir: The first group had previous genotyping of virus in HIV RNA and/or cellular HIV DNA; the second group had no historical genotype available. The researchers defined virologic failure as two consecutive viral loads above 50 copies. They determined antiretroviral susceptibility and genotypic susceptibility score with the ANRS v26 algorithm. Thymidine analog mutations (TAMs) considered were 41L, 67N, 210W, and changes at position 215, which affect susceptibility to abacavir or tenofovir.
Participants switched to elvitegravir/cobicistat/tenofovir/emtricitabine or to dolutegravir/abacavir/lamivudine from two nucleos(t)ides plus a nonnucleoside (35%), a protease inhibitor (36%), or an integrase inhibitor (17%), or from a different regimen (12%). Fifty-one of 75 people (68%) had a previous genotype, while the remaining 24 (32%) did not. In the genotyped group, 24 switched to elvitegravir and 27 to dolutegravir; in the no-genotype group, 14 switched to elvitegravir and 10 to dolutegravir.
Time since HIV diagnosis was similar in the two groups (median 19 years overall), as was time on antiretroviral therapy (median 17 years overall). The genotyped group had a viral load below 50 copies for a median of 6 years, compared with 9 years in the no-genotype group. About two thirds of participants switched to the STR to simplify therapy, while most of the rest switched to avoid toxicity.
In the 51 people with previous genotyping, a median of 8.9 years elapsed between the last genotype and the current switch. Forty-six had HIV RNA genotyping only, 4 had HIV DNA genotyping only, and 1 had both RNA and DNA genotyping. Reverse transcriptase resistance data were available for 50 people, reverse transcriptase plus integrase data for 12 people, and integrase data for 1 person. Twenty-seven people genotyped for reverse transcriptase mutations (54%) had one or more mutations; 3 people genotyped for integrase mutations (23%) had one or more mutations. Two people with an archived T97A integrase mutation switched to elvitegravir, and 1 switched to dolutegravir.
The M184V mutation was by far the most frequent archived reverse transcriptase mutation detected, appearing in 88% of reverse transcriptase genotypes. M184V appeared alone or with fewer than two TAMS in 35% of genotypes, with two or more TAMs in 19%, with K65R (the tenofovir mutation) in 15%, with L74I/V and two or more TAMs in 15%, and with L74I/V alone in 4%.
Through a median 13 months of follow-up, 1 person in the genotyped group (2%) and none in the no-genotype group had virologic failure. Four people in the genotyped group (8%) and 2 in the no-genotype group (8%) interrupted their STR regimen without virologic failure. The overall success rate was 90% in the genotyped group and 92% in the no-genotype group. Five people (3 on elvitegravir and 2 on dolutegravir) stopped their STR because of toxicity. One person died of hepatocellular carcinoma. And one person stopped the elvitegravir STR for virologic failure 2.3 years after switching. The person with virologic failure had taken several previous antiretroviral regimens, had prior virologic failures, had a record of poor adherence, and had never taken an integrase inhibitor.
The researchers concluded that an integrase inhibitor STR can maintain virologic suppression in people with deep antiretroviral experience, including those with a record of archived reverse transcriptase or integrase resistance mutations.
Reference
1. Pronier C, Maillard A, Comacle P, et al. Successful switch to once-daily single-tablet regimen (STR) containing elvitegravir (EVG) or dolutegravir (DTG) in virologically suppressed HIV-1-infected patients despite archived resistant quasispecies. 9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris. Abstract MOPEB0320.
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