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Sofosbuvir + daclatasvir demonstrates high cure rates for people with HIV and HCV co-infection
Liz Highleyman, 2015-10-21 08:10:00

Nearly all people with HIV and genotype 1-4 HCV co-infection treated for 12 weeks with an interferon-free regimen of sofosbuvir (Sovaldi) plus daclatasvir (Daklinza) achieved sustained virological response in the ALLY-2 trial, but 8 weeks did not work as well, according to a recent report in the New England Journal of Medicine. Sub-studies presented this month at IDWeek 2015 showed that this regimen is highly effective regardless of race or specific antiretroviral regimen.

The advent of direct-acting antiviral agents (DAAs) that can be used in all-oral regimens has revolutionised hepatitis C treatment, offering options that are shorter, better tolerated and more effective than interferon-based therapy. This is particularly beneficial for HIV-positive people co-infected with hepatitis C virus (HCV), who tend to have more rapid liver disease progression and do not respond as well to interferon.

David Wyles of the University of California at San Diego and fellow investigators with the ALLY-2 trial evaluated a combination of Gilead Sciences' HCV NS5B polymerase inhibitor sofosbuvir and Bristol-Myers Squibb's NS5A inhibitor daclatasvir without interferon or ribavirin. Results were previously presented in part at this year's Conference on Retroviruses and Opportunistic Infections (CROI).

This open-label study included 151 HIV/HCV co-infected participants who had not received prior hepatitis C treatment and 52 treatment-experienced patients. Nearly 90% were men, about 60% were white, about 35% were black and the median age was approximately 55 years; 14% had compensated liver cirrhosis. More than 80% had HCV genotype 1 (68% with harder-to-treat subtype 1a), while about 15% had genotypes 2 or 3 and a small number had genotype 4.

Almost all participants were on antiretroviral therapy (ART), mostly with undetectable HIV viral load, and the median CD4 count was above 500 cells/mm3. Those on ART were permitted to use a wide variety of antiretrovirals. About half were taking HIV protease inhibitors with most of the rest on NNRTIs or integrase inhibitors.

Previously untreated participants were randomly assigned to receive 400mg sofosbuvir plus 60 mg daclatasvir once-daily for either 8 or 12 weeks, while treatment-experienced patients were all treated for 12 weeks. Daclatasvir doses were adjusted when administered with specific antiretroviral medications based on prior drug interaction studies (down to 30mg when used with ritonavir-boosted HIV protease inhibitors or up to 90mg when used with most NNRTIs).

The primary study endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12).

Overall SVR12 rates were 97% for previously untreated people treated for 12 weeks, 76% for those treated for 8 weeks and 98% for treatment-experienced people treated for 12 weeks. Most relapses occurred in the 8-week treatment arm.

Looking at genotype 1 alone, cure rates were about the same: 96.4%, 75.6% and 97.7%, respectively. Everyone with genotypes 2, 3 or 4 achieved sustained response. People with cirrhosis had somewhat lower SVR12 rates in all treatment arms.

Sofosbuvir plus daclatasvir was generally safe and well-tolerated. Serious adverse events were uncommon (< 3% across treatment arms) and there were no adverse events leading to treatment discontinuation. The most common side-effects were fatigue, nausea and headache. Participants maintained HIV viral suppression and stable CD4 counts.

These findings show that sofosbuvir plus daclatasvir taken for 12 weeks is safe and effective for HIV/HCV co-infected people, the study authors concluded. These results support current hepatitis C treatment guidelines recommending that HIV-positive and HIV-negative people should be treated the same for hepatitis C after taking into account interactions with antiretrovirals.

As described in another study presented at CROI, Gilead's combination of sofosbuvir and its NS5A inhibitor ledipasvir (the drugs in Harvoni) was also highly effective for HIV/HCV co-infected people with genotype 1 in the ION-4 trial. Daclatasvir, however, is active against other HCV genotypes that are more common outside the U.S. (known as 'pangenotypic').

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