HIV/HCV co-infected people taking the experimental
hepatitis C virus polymerase inhibitor sofosbuvir (formerly GS-7977)
experienced a rapid decline in HCV viral load similar to that seen in
HIV-negative patients, researchers reported on Wednesday at the 52nd
Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San
Francisco. Side-effects were also similar and there was no sign of interactions
with antiretroviral drugs in this 14-day study.
people with hepatitis C tend to experience more rapid liver disease progression
than HIV-negative individuals and do not respond as well to interferon-based
treatment. Adding new direct-acting anti-HCV drugs can improve response, but
raises concerns about worsened side-effects and interactions with anti-HIV drugs. Furthermore,
many co-infected people are considered ineligible for interferon-based therapy
or cannot tolerate its side-effects, and await more effective interferon-free
is a once-daily nucleotide analogue HCV NS5B polymerase inhibitor active
against multiple HCV genotypes. Studies of HIV-negative people with hepatitis C
have shown that sofosbuvir alone or in combination with ribavirin or other
direct-acting HCV drugs is well tolerated and has a high cure rate.
Stephen Rossi from Gilead Sciences presented the first data on sofosbuvir in
HIV/HCV co-infected people. This phase Ib trial looked hepatitis C viral
kinetics (speed and slope of viral decline) while taking 400mg sofosbuvir
once daily for seven days. Researchers also assessed tolerability, effect on
HIV control and drug-drug interactions with antiretrovirals.
included 30 HIV/HCV co-infected people in Puerto Rico. About 80% were men, 57%
were white, 43% were black and the average age was 53 years. About 75% had
difficult-to-treat HCV genotype 1 (more than two-thirds with 1a), four had
genotype 2, three had genotype 3 and one had the uncommon genotype 4.
were on stable antiretroviral therapy for at least one month and all but one had
undetectable HIV viral load. They had well-preserved immune function with a
median CD4 cell count of 600 cells/mm3, a median CD4 cell
percentage of 31%, and had had no opportunistic infections or other HIV
complications during the past six months.
common antiretroviral regimen, taken by one-third of participants, was
efavirenz/tenofovir/emtricitabine (the drugs in the Atripla coformulation). Eight were taking ritonavir-boosted
atazanavir (Reyataz) plus
tenofovir/emtricitabine (the drugs in Truvada),
three were taking raltegravir (Isentress)
plus tenofovir/emtricitabine and the rest were on other regimens.
load declined rapidly after starting sofosbuvir, falling by more than 2 log10
IU/mL during the first 24 hours. The median decline was more than 4 log10
IU/mL at the end of the seven-day dosing period. HCV RNA continued to
drop for two days after stopping sofosbuvir, then began increasing, but did not
return to the baseline level by the end of follow-up at 14 days.
On the last
day of dosing, approximately 40% of participants had undetectable HCV viral
load. This proportion approached 60% two days after stopping the drug and
remained at about 15% on the last day of follow-up.
of decline was similar for all HCV genotypes, was generally consistent
regardless of antiretroviral regimen and also matched viral kinetics seen in
prior studies of HIV-negative patients with hepatitis C alone.
patients – who do not
do as well on interferon-based therapy – responded as well as white patients
to sofosbuvir. A comparison of responses according to participants' IL28B
status was not presented, but Rossi said a large proportion of people in Puerto
Rico have the unfavourable CC gene pattern and this analysis is forthcoming.
was generally well tolerated in this short study, with a safety profile similar
to that of HIV-negative hepatitis C patients. All adverse events were
mild to moderate, and no single side-effect was seen in more than one person.
There were no treatment-emergent grade 3-4 laboratory abnormalities and no
significant change in hematologic parameters– an important point as some HCV
drugs can cause anaemia or neutropenia.
of HIV breakthrough was observed and all participants who started with
undetectable HIV RNA maintained viral suppression. Four people experienced HIV
viral 'blips', but these subsequently fell below the level of detection. There
were also no clinically significant changes in absolute CD4 cell count or CD4
sofosbuvir interactions with antiretroviral therapy is underway, but the modest
side-effects and lack of changes in HIV parameters suggests major concerns are
HCV early viral kinetics was observed in HIV/HCV- and HCV- infected patients and support further
study of sofosbuvir in HIV/HCV co-infected patients," the researchers
Rossi noted that a phase III trial of sofosbuvir
for HIV/HCV co-infected people is currently enrolling in the US and will
start in Europe later this year. The sofosbuvir development program is one of
the first to test an HCV drug for co-infected people in parallel with HCV
monoinfected people. He projected that Gilead may file for US approval of
sofosbuvir by the middle of 2013.