Doctors in the US state of Maryland have issued preliminary
guidance for the use of hepatitis C protease inhibitors by patients co-infected
with HIV. Published in the online edition of Clinical Infectious Diseases, the provisional recommendations
support use of the protease inhibitors in selected groups of co-infected patients.
“The benefits of including these medications will outweigh
the risks for some individuals,” comment the authors.
In May 2011 the protease inhibitors boceprevir and
telaprevir were approved in the US for the treatment of chronic hepatitis C genotype
1 infection. In clinical trials, involving hepatitis C-mono-infected
individuals, the use of these drugs in combination with pegylated interferon
and ribavirin improved rates of sustained virological response by between 25%
Clinical trials into the safety and efficacy of these
hepatitis C protease inhibitors are currently underway involving patients
co-infected with HIV.
Hepatitis C is a leading cause of serious illness and death
in co-infected patients. There is therefore considerable interest in the
potential role of boceprevir and telaprevir in the hepatitis C therapy of
An opinion was therefore provided to the Maryland AIDS
Assistance Program on what is known about the safety and efficacy of these
drugs in co-infected patients, and which patients could be considered
candidates for their off-label use.
The authors believe the opinion “may be useful to others.”
Published data on the safety and efficacy of these drugs in
co-infected patients are scarce.
However, results of a phase 2 study evaluating telaprevir
are available. The study involved 59 individuals. These included 13 patients
not currently taking HIV therapy because their HIV infection was well controlled.
A further 13 patients treated with efavirenz (Sustiva) and FTC/tenofovir (Truvada)
and 24 individuals taking ritonavir-boosted atazanavir (Reyataz) and Truvada were
also recruited to the study.
All received standard hepatitis C therapy consisting of
pegylated interferon and ribavirin lasting 48 weeks. However, for the first
twelve weeks of therapy, the patients were randomised to receive either
telaprevir or a placebo. The dose of telaprevir was 750 mg, taken at intervals
of approximately eight hours. The drug was taken with food with a high fat
content. After four weeks of treatment, 70% of patients in the telaprevir arm
had an undetectable hepatitis C viral load compared to 5% of individuals taking
the placebo. Twelve-week outcomes also favoured telaprevir.
The treatment appeared safe and there were no unexpected
side-effects. HIV remained well controlled. However, two patients experienced
an increase in their hepatitis C viral load probably due to resistance.
Complete safety and efficacy results are expected in 2013.
Results of a phase 2 study evaluating boceprevir are also
available. The research involved 99 co-infected patients and lasted 48 weeks.
It had two stages. For the first four weeks, all the patients were treated with
pegylated interferon and ribavirin. They were then randomised on a 2:1 basis to
take either a thrice-daily 800 mg dose of boceprevir or a placebo.
Patients were ineligible for the study if they were taking
AZT, ddI (Videx), d4T (stavudine, Zerit), efavirenz (Sustiva), etravirine (Intelence),
or nevirapine (Viramune).
Ritonavir-boosted protease inhibitors and raltegravir (Isentress) were permitted.
Four weeks after randomisation, 38% of
patients in the boceprevir arm had an undetectable hepatitis C viral load compared
to 15% of those taking a placebo. Similarly, at week 24, some 71% of patients
taking the protease inhibitor still had suppressed hepatitis C viral load
compared to 34% of individuals taking the placebo. Rates of treatment discontinuation
were broadly similar between the two study arms. Complete results of the study
are expected in 2013.