TreatmentUpdate
213

February 2016 

Zepatier in HCV and HIV co-infection

Due to shared routes of infection, some people are infected with two viruses—HIV and HCV. This state is called co-infection. Researchers in North America, Western Europe, Australia and Israel recruited 218 participants who were co-infected with HIV and HCV to participate in a 12-week trial of Zepatier. Results showed that Zepatier had high rates of cure in co-infected people with HCV genotypes 1a, 1b, and 4.

Study details

The average profile of participants upon entering the study was as follows:

  • age – 49 years
  • 84% men, 16% women
  • the distribution of the main HCV genotypes was as follows: GT1a – 66%; GT1b – 20%; GT4 – 13%
  • cirrhosis was present in 16% of participants
  • CD4+ count – 568 cells/mm3
  • 97% of participants were taking potent combination anti-HIV therapy (commonly called ART)

Results

In an analysis that excluded participants who were cured with Zepatier but then became reinfected or who left the study for reasons unrelated to treatment, researchers found that, overall, 98% of participants were cured. That is, 203 out of 208 participants had an undetectable level of HCV both at 12 and 24 weeks after the cessation of Zepatier.

By genotype

Here are the rates of cure distributed by genotype:

  • GT1a – 97% (135 out of 139 people) were cured
  • GT1b – 100% (42 out of 42 people) were cured
  • GT4 – 96% (26 out of 27 people) were cured

Relapse and reinfection

A total of five participants relapsed; none of these participants had cirrhosis. Four of them had GT1a and one had GT4.

Four of the five participants who relapsed were taking ART, so their relapse is not likely due to a weakened immune system as a result of HIV infection.

Two participants were re-infected. The first entered the study having GT1a and after this was cured technicians detected a new strain—GT3.

The second participant was initially infected with GT1b and after this was cured technicians found that he was reinfected with GT3.

Resistance in HCV

If left untreated, HCV-infected cells produce many copies of the virus and a small proportion of these copies can have naturally occurring changes, or mutations, that may help them to at least partially resist the effect of treatment. At the start of the study, technicians assessed blood samples from many participants who were infected with GT1a, because this was the most common strain of the virus. In 63% of these cases (91 out of 141 participants), there were no cases of HCV with the ability to resist treatment. Furthermore, in these 91 participants, 98% were cured.

However, technicians found that the remaining 53 participants had HCV with the capacity to resist treatment with Zepatier. Yet when treated with this drug, 94% (50 out of 53 participants) were cured.

So, at least in this study, Zepatier may be sufficiently strong to overcome naturally occurring mutations in HCV that can confer some degree of resistance to therapy.

Adverse events

“Adverse events” is a term used in clinical trials that refers to a broad array of unfortunate events that can occur during a trial. Some adverse events may be related to exposure to the study medicines and are called side effects. Other adverse events may be unrelated to the study medicines.

Here are some common side effects that occurred:

  • lack of energy and/or unexpected tiredness – 13%
  • headache – 12%
  • nausea – 9%

No participants left the study due to side effects. During the study, one person developed a seizure and another person was diagnosed with pneumonia. It is not clear if either of these were related to exposure to Zepatier.

No one died while in the study.

HIV-related assessments

During the study, two participants developed elevated levels of HIV in their blood despite their use of ART. When nurses intervened and interviewed the participants, they determined that these participants were not taking all of their HIV medicines exactly as directed. The nurses provided education reinforcing the importance of adherence. The HIV viral loads in these two participants subsequently became undetectable.

Overall, CD4+ cell counts did not significantly change during the study.

Key points

The present study found that Zepatier was effective and well tolerated in patients with GT1 and GT4. Rates of cure were high, usually greater than 90%.

—Sean R. Hosein

REFERENCE:

Rockstroh JK, Nelson M, Katlama C, et al. C-Edge co-infected: final results from phase III study of elbasvir and grazoprevir in patients with HCV and HIV. American Association for the Study of the Liver Disease, 13-17 November 2015. Abstract 210.

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