March 16, 2015
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Optimized Tivicay shows early efficacy in patients with INSTI-resistant HIV-2

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Regimens that included Tivicay showed significant initial efficacy as salvage therapy in ART-experienced patients with HIV-2 who were resistant to first-generation integrase inhibitors, according to researchers in Paris.

Tivicay (dolutegravir, ViiV Healthcare) was approved in France in 2014. According to the researchers, dolutegravir retains activity against viruses resistant to the earlier integrase strand transfer inhibitors (INSTIs) Isentress (raltegravir, Merck) and Vitekta (elvitegravir, Gilead Sciences).

“Since December 2011, dolutegravir was available … for salvage therapy in patients infected with INSTI-resistant HIV-1 and HIV-2, and experiencing treatment failure without any treatment options,” the researchers wrote in Clinical Infectious Diseases.

The researchers evaluated 13 adult patients with HIV-2 who were enrolled in the French Named Patient Program (NPP). All patients had virological failure to a raltegravir-containing regimen, and had INSTI-resistance–related mutations. The patients had a median 15 years of infection duration and had been given 16 previous ART regimens.

The patients received a regimen of dolutegravir 50 mg open-label, twice daily, with optimized background ART combinations, based on previous treatment failures and/or genotypic resistance tests conducted at baseline. Their viral load was measured at 3 months and 6 months, and median follow-up occurred at 9 months.

The median baseline plasma viral load was 9,544 copies/mL, and the median CD4 cell count was 100/mm3. The following integrase genotypic resistance patterns were determined: Y143C/G/H/R (n = 5), Q148K/R/S (n = 2) and N155H (n = 4).

Optimized ART regimens included nucleoside reverse transcriptase inhibitors (tenofovir disoproxil fumarate [n = 3], zidovudine [n = 4], lamivudine or emtricitabine [n = 8], abacavir [n = 3] and didanosine [n = 1]), associated with ritonavir-boosted Prezista (darunavir, Janssen) 600/100 mg twice-daily DRV/r (n = 12), ritonavir-boosted Invirase (saquinavir, Hoffmann La Roche) 1,000/100 mg twice daily (SQV/r, n = 3) and Selzentry (maraviroc, ViiV Healthcare) 150 mg twice daily (n = 3).

At 3 months, plasma viral load could not be detected in six patients, and at 6 months, viral load was undetectable in all 13 patients. Median CD4 cell count was 161/mm3 at 3 months and 167/mm3 at 6 months. With the exception of one death due to progressive multifocal leukoencephalopathy at 4 months, no serious events were reported.

According to the researchers, further studies are warranted on the use of dolutegravir-containing regimens for salvage therapy in this patient population.

“These preliminary results demonstrated for the first time that dolutegravir containing regimens might provide a substantial initial efficacy rate for salvage therapy in heavily antiretroviral-experienced HIV-2–infected patients harboring virus without the Q148 or N155 integrase inhibitors mutation profiles,” they wrote. “Cross-resistance of first generation INSTI with dolutegravir seems to be higher in HIV-2 than in HIV-1. Larger patient numbers and longer follow-up are warranted in order to confirm these findings.” – by Jen Byrne

Disclosure: The researchers report no relevant financial disclosures.