Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial

The Lancet Infectious Diseases, Early Online Publication, 12 June 2013

doi:10.1016/S1473-3099(13)70149-X

Prof Mark Sulkowski MD a, Prof Stanislas Pol MD b, Josep Mallolas MD c, Hugo Fainboim MD d, Curtis Cooper MD e, Jihad Slim MD f, Antonio Rivero MD g, Carmen Mak PhD h, Seth Thompson PhD h, Anita YM Howe PhD h, Larissa Wenning PhD h, Peter Sklar MD h, Janice Wahl MD h, Dr Wayne Greaves MD h , for the P05411 study investigators†

Summary

Background

Rates of sustained virological response (SVR) to peginterferon—ribavirin are low in patients with hepatitis C virus (HCV) genotype 1 and HIV. We aimed to assess efficacy and safety of triple therapy with boceprevir plus pegylated interferon alfa-2b (peginterferon) and ribavirin, which increases rates of SVR in patients with HCV alone.

Methods

In our double-blind, randomised controlled phase 2 trial, we enrolled adults (18—65 years) with untreated HCV genotype 1 infection and controlled HIV (HIV RNA <50 copies per mL) at 30 academic and non-academic study sites. We randomly allocated patients (1:2) according to a computer generated sequence, stratified by Metavir score and baseline HCV RNA level, to receive peginterferon 1·5 μg/kg per week with weight-based ribavirin (600—1400 mg per day) for 4 weeks, followed by peginterferon—ribavirin plus either placebo (control group) or 800 mg boceprevir three times per day (boceprevir group) for 44 weeks. Non-nucleoside reverse-transcriptase inhibitors, zidovudine, and didanosine were not permitted. The primary efficacy endpoint was SVR (defined as undetectable plasma HCV RNA) at follow-up week 24 after end of treatment. We assessed efficacy and safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00959699.

Findings

From Jan 15, 2010, to Dec 29, 2010, we enrolled 99 patients, 98 of whom received at least one treatment dose. 40 (63%) of 64 patients in the boceprevir group had an SVR at follow-up week 24, compared with ten (29%) of 34 control patients (difference 33·1%, 95% CI 13·7—52·5; p=0·0008). Adverse events were more common in patients who received boceprevir than in control patients: 26 (41%) versus nine (26%) had anaemia, 23 (36%) versus seven (21%) pyrexia, 22 (34%) versus six (18%) decreased appetite, 18 (28%) versus five (15%) dysgeusia, 18 (28%) versus five (15%) vomiting, and 12 (19%) versus two (6%) neutropenia. Three patients who received boceprevir plus peginterferon—ribavirin and four controls had HIV virological breakthrough.

Interpretation

Boceprevir in combination with peginterferon—ribavirin could be an important therapeutic option for patients with HCV and HIV.

Funding Merck.

Source

Am I Number 12 ?

Electron micrographs of hepatitis C virus purified from cell culture. Scale bar is 50 nanometers.
Courtesy of the Center for the Study of Hepatitis C, The Rockefeller University.
Pix - wikipedia

Sunday, Jun 23, 2013

Dr Th Dhabali Singh

When the fact that Hepatitis C deaths are more than HIV/AIDS related deaths in Manipur was revealed by the Opposition leader in Manipur Assembly a few days ago and the same was published in different morning dailies the next day, many people must have been caught unawares. The severity of the prevalence of Hepatitis C in Manipur was also previously made known through the 11th February 2013's edition of The Telegraph in its front-page news with the headline "Manipur worst hit by Hepatitis C".

In this news, besides highlighting Hepatitis C prevalence in Manipur, the Centre was urged to provide a separate budget for tackling Hepatitis C and also the inclusion of drugs used for the treatment on the list of National Essential Medicines. Because of the high number of intravenous drug users, Manipur has been the worst hit amongthe North-Eastern states. Second comes Nagaland and the third is Mizoram. Manipur's case is unique because of the high HIV/Hepatitis C co-infection rate and according to a recent survey conducted by the Indian Council of Medical Research, 98 percent of HIV-infected people in Churachandpur district were co-infected with Hepatitis C.

AM I NUMBER 12?

One in 12 people worldwide is living with either chronic Hepatitis B or C. The numbers are absolutely staggering and the prevalence is far higher than HIV or any cancer. While the public awareness about HIV is high mainly due to relentless campaigns and the media, the awareness of Hepatitis B or C is abysmally low and the majority of those infected are unaware. In 2008, the World Hepatitis Alliance launched the global awareness programme under the banner, 'Am I Number 12?' to communicate the fact that one in 12 people worldwide is living with either chronic Hepatitis B or C. The campaign encourages people to question themselves rather than stigmatise others and to GET TESTED if they think they could be at risk.

HEPATITIS B AND HEPATITIS C

Hepatitis B and Hepatitis C represent two of the major threats to global health. Because many people feel no symptoms, both Hepatitis B and C are 'silent' viruses, and one could be infected for years without knowing it. Both Hepatitis B and C can lead to liver cirrhosis where one is exposed to life-threatening complications such as bleeding, ascites, liver cancer and liver failure.

Hepatitis B virus is highly infectious and about 50-100 times more infectious than HIV. The virus is transmitted through blood and other body fluids like saliva, semen and vaginal fluid of an infected person. According to the World Health Organisation (WHO) estimates, two billion people have been infected with the Hepatitis B virus worldwide and approximately 350 million people are living with chronic infections. Unlike Hepatitis C, there is a vaccine that can prevent the infection.

Four out of five people infected with Hepatitis C develop chronic infection, which may cause cirrhosis and liver cancer after 15-30 years. Hepatitis C is spread mainly through blood-to-blood contact, and like Hepatitis B, usually, there are no obvious symptoms. WHO estimates that about three to four million people are newly infected with Hepatitis C every year.

DIAGNOSIS AND TESTS

For Hepatitis B: To diagnose the infection of Hepatitis B, the blood needs to be checked for the Hepatitis B surface antigen (HBsAg). The HBs is a part of the virus that mostly appear six to twelve weeks after infection. If the test is positive, it is very likely that one has Hepatitis B and further tests are required for confirmation, to check if the infection is new or old and, to see if one needs treatment or not.WHO recommends that all blood donations are tested for this marker to avoid transmission to recipients.Other tests include:

* Testing for antibodies to Hepatitis B surface antigen – A positive test indicates that one has naturally cleared the virus or has been vaccinated against it. Having antibodies to Hepatitis B (anti-HBs) is actually good because it means one is protected against future infection by the virus and is no longer contagious.

* Testing for antibodies to Hepatitis B core antigen –A positive test means one has had a recent infection or an infection in the past. A positive test for antibodies to Hepatitis B core antigen combined with a positive HBsAg indicates one has chronic infection.

* Hepatitis B virus DNA polymerase chain reaction (PCR) test – HBV DNA PCR is used for both Qualitative as well as Quantitative (viral load) testing.

For Hepatitis C: The blood is checked for HCV antibodies (anti-HCV). If the test is positive, it means either one is infected with it or was infected with it but has already cleared the virus. The test is mandatory for blood donations in almost all countries. Hepatitis C antibodies usually take seven to nine weeks to appear in the bloodstream after infection. Hepatitis C virus RNA testing is used to confirm the diagnosis. PCR detection of Hepatitis C virus-RNA in serum is mostly used to confirm acute Hepatitis C infection and also to identify viraemia in the chronic disease, particularly in anti-Hepatitis C virus antibody-negative individuals.

AWARENESS CAN CHECK THE SPREAD OF HEPATITIS B AND C

World Hepatitis Day is observed every year on July 28 and on this day, health authorities and NGOs across the world hold special programmes to make people aware of these viral infections. Hepatitis C has claimed more lives than HIV because the cost of medicines is very high, and presently, in India there is no government policy to help patients as in the case of HIV/AIDS. A patient has to spend six to eight lakh rupees annually for treatment. Unlike HIV/AIDS, there is no official data as there is no survey conducted to know the exact status of Hepatitis C or B in Manipur.

Spreading awareness remains the key to fighting against Hepatitis B and C. Like in one of the poster campaigns for World Hepatitis Day says, "The clock is ticking. Act now to protect a new generation."

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* Dr Th Dhabali Singh wrote this article for The Sangai Express
The writer is Senior Consultant Pathologist and Managing Director, BABINA Diagnostics, Imphal
This article was posted on June 22, 2013.