Hepatitis C Coinfection Studies

Boceprevir: SVR-12 Results in HIV/HCV Coinfection

SVR results at 12 weeks after treatment from a randomised double-blind, placebo controlled study of Merck’s boceprevir (BOC) with pegylated interferon (peg-IFN) + ribavirin (RBV) in 98 patients with HIV and HCV genotype-1 coinfection were presented by Mark Sulkowski. [2]

In this study, all patients were on stable antiretroviral treatment (not including NNRTIs, AZT or ddI) with suppressed viral load (<50 copies/mL). ART regimen included atazanavir/r (n=31), lopinavir/r (n=25), darunavir/r (n=17), other PI (n=7), raltegravir (n=10) and other (n=2).

Patients were randomised (2:1) ratio to receive boceprevir 800 mg every eight hours (n=64) or placebo (n=34) plus pegylated interferon-alfa-2b (Peg-Intron) and weight-based RBV (600 to 1400 mg/day). All patients also had a four-week lead-in phase with peg-IFN + RBV.

Baseline characteristics included: mean age of 45 years; 69% male; 82% white. 88% had HCV RNA >800,000 IU/mL and 65% were genotype 1a. Median CD4 counts were approximately 580 cells/mm3 (range 200 - >1,500). Only 4 patients had cirrhosis.

HCV RNA levels were undetectable in 59% vs 23% of patients at week 12 and 64% vs 29% at week 48 in the boceprevir vs control groups with SVR rates 12 weeks after the end of treatment of 61% vs 26% (see Table 2).

Table 2: Interim HCV RNA BLQ (%) Response Rates With Boceprevir in HIV/HCV Coinfection

B: boceprevir; P: peg-IFN; R: ribavirin.

Important Drug Interactions Between HIV PIs and Boceprevir

A late breaker poster was presented by researchers at Merck reporting significant drug interactions between boceprevir and HIV protease inhibitors (atazanavir, lopinavir and darunavir) in HIV negative volunteers. [3] This highlighted not just the complexity for future HCV treatment in people already on ART, but also the importance of conducting major drug-drug interaction studies prior to coadministration in new studies.

Boceprevir significantly decreased the exposure of the PIs by up to 41-75% for AUC0-last, Cmax, and Cmin [GMR (90% CI)]. Coadministration with boceprevir also decreased the exposure of ritonavir AUCt by 34%, 22%, and 27% in the atazanavir, lopinavir and darunavir groups, respectively. Co-administration with atazanavir/r did not alter boceprevir AUCt, but co-administration with lopinavir/r and darunavir/r decreased boceprevir AUCt 45% and 32%, respectively.

Table 3: Geometric Mean Ratio (90% CI) for Interaction Between Boceprevir and HIV PIs

Comment

These results are important for people with HCV genotype 1 who are in need of urgent treatment.

The interaction data between these HCV drugs and antiretrovirals in these studies was luckily not associated with high rates of treatment failure.

For further information on HCV drug interactions please see the excellent online resource produced by the pharmacology team at Liverpool University.

www.hep-druginteractions.org/

UK consensus guidelines for use of these new HCV drugs were recently published online with free access, and although are not HIV-specific, they include a reference to coinfection being a population where their use should be considered. [4]

References

Unless stated otherwise, all references are to the Programme and Abstracts for the 19th Conference of Retroviruses and Opportunistic Infections, 5–8 March 2012, Seattle.

1. Dieterich D et al. Telaprevir in combination with pegylated interferon-alfa-2a+RBV in HCV/HIV-co-infected patients: a 24-week treatment interim analysis. Oral abstract 46.

   www.retroconference.org/2012b/Abstracts/42969.htm

2. Sulkowski M et al. Boceprevir + pegylated interferon + ribavirin for the treatment of HCV/HIV-co-infected patients: end of treatment (week-48) interim results. Oral abstract 47.

   www.retroconference.org/2012b/Abstracts/44725.htm

3. Hulskotte E et al. Pharmacokinetic interaction between the HCV protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, lopinavir, and darunavir. Poster late breaker 771LB.

   www.retroconference.org/2012b/Abstracts/45463.htm

4. Ramachandran P et al. UK consensus guidelines for the use of the protease inhibitors boceprevir and telaprevir in genotype 1 chronic hepatitis C infected patients. Aliment Pharmacol Ther, 2012, 35(6): 647-662. Free full access.

   onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2012.04992.x/full

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