Hepatitis C Report from the Retrovirus Conference: report 1
- (There are several interesting things in this report, but I found the
paragraph on HCV in brain tissue interesting in particular.)
NATAP - www.natap.org
9th Retrovirus Conference
Report from Jules Levin
Hepatitis C Report from the Retrovirus Conference: report 1
Several studies at Retrovirus reported HIV accelerates HCV
progression, and coinfected patients get sick more often: they more
often experience any grade 4 clinical event and grade 4 liver-related
events, and quicker death (abstract 657-M, Reisler; abstract 658-M,
Rimland). This is in part due to the populations infected with both
HIV and HCV.
HIV May Impair Immune Response to HCV
Several basic science in vitro (test tube) studies reported at
Retrovirus show HCV/HIV coinfected patients have an impaired immune
response to HCV, even though they can respond well to HIV and have
good CD4 counts and low HIV viral load (abstract 640-M, Lauer, Mass
General; abstract 121, Torriani, UCSD).
One study reported 20% of the 400 HCV/HIV coinfected patients at
Virginia Commonwealth University and Medical College of Virginia were
women. 86% were African-American, and 75% reported IVDU as the main
risk factor for getting HCV (abstract 664-M, Tsogas).
HCV May be in Brain & Cervical Lavage (CVL)
Nine HCV/HIV positive women from the WIHS (Women Inter-Agency HIV
Study) were tested for HCV RNA in plasma and cervical lavages (CVL).
HCV RNA was detected in the blood and plasma of 5/9 women (abstract
648-M, Nowicki, USC). The authors suggest there may be a separate
compartment for HCV in CVL and this may play a role in vertical
(pregnant women-to-newborn) and sexual transmission.
HCV-infected patients have reported experiencing fatigue, depression,
and emotional distress & anxiety. Several studies have suggested this
is true and that HCV may be able to enter the brain. A study at
Retrovirus reported that HCV RNA was found in autopsy brain tissue
samples from 3 of 6 patients tested (one patient was HIV+). (abstract
649-M, Laskus, Mayo Clinic). The type of HCV strain found suggested
that HCV could replicate in the brain. The findings suggested HCV
could be carried across the blood-brain barrier by HCV-infected
lymphoid cells in a process similar to that in HIV.
Poor Care For Coinfected: 40% coinfected in SF care system
Marion Peters and a group from UCSF reported on 4000 HIV+ patients
and hepatitis patterns in the San Francisco Community Health Network
from June 1996 to July 2000. Hepatitis test results were available
for 2900 patients (76%). 40% had HCV and 9% HBV. Many patients with
hepatitis had normal ALT (liver enzymes). High rates of persistently
elevated ALT levels among coinfected patients may predict advancing
liver disease. Doctors were providing HIV HAART treatment less often
to HCV-infected patients, regardless of their HIV disease status,
lifestyle, and ALT levels (abstract 662-M).
HCV/HIV coinfected patients are not receiving hepatitis A vaccines
and drink too much. The US Public Health service Guidelines recommend
hepatitis A vaccine for coinfected patients, and advises they abstain
from alcohol to avoid progression to liver failure. Teshale from the
CDC (abstract 665-M) analyzed data from 14,000 patients from the
Adult/Adolescent Spectrum of HIV Disease project (1998-2001). This is
an ongoing observational database of HIV+ patients in 11 cities. 13%
of patients were reported to be coinfected with HIV and HCV. I
suggest this is an underestimate, when compared to the many other
studies finding higher rates. The underestimate could perhaps be due
to not adequately testing all HIV+ persons. 26% of coinfected persons
were female. 45% were black, 28% were white, and 26% were Hispanic.
50% were IVDUs, 17% were men who have sex with men, and 34% were
IVDU/MSM. Perhaps most important, only 6% of the coinfected and 7% of
the HIV only-infected were vaccinated for hepatitis A. 36% of
coinfected patients used alcohol before being tested for HCV and 20%
reported drinking after learning they had HCV. The authors
recommended education and awareness programs be provided to doctors
regarding the need to vaccinate coinfected patients with the
hepatitis A vaccine, and to help coinfected patients stop using
Pegylated Interferon (Pegasys) plus Ribavirin Treatment in Coinfected
Patients: 80% had high viral load & genotype 1
ACTG study 5071 compares the effectiveness & safety of Pegasys +
ribavirin to standard interferon + ribavirin. Patients with
compensated cirrhosis were permitted into the study. As well patients
with CD4 >100 and HIV viral load <10,000 on stable ART were permitted
to enter study. But for patients who were HIV treatment-na�ve their
CD4 count had to be >300. 133 patients were randomized to receive
pegasys 180 ug once per week by subcutaneous injection or standard
interferon 6 MIU 3 times per week for 12 weeks followed by 3 MIU 3
times per week, also by subcutaneous injection. All study patients
started therapy with 600 mg of ribavirin per day and increased dose
to 1000 per day. This was done to limit the side effects during the
initial stages of therapy and to improve remaining on study drug.
Study treatment is for 48 weeks with a 24 week followup period. The
sustained virologic response is evaluated at the 72 week time-point.
80% of the study patients were men; 33% African-American; 14%
Hispanic; 49% White;45 years old; median CD4 count was 450-500; 60%
of patients had <500 copies/ml; 90% were on HIV therapy. The median
Karnofsky score was 90.
The average HCV viral load was 6.2 million; 83% of patients had >6
million viral load. And 78% had genotype 1; 68% had abnormal ALT;
median HAI score 5.0 (out of 18); median fibrosis score 2.5; 10% had
cirrhosis (fibrosis score 5-6). So, the two patient groups were
By intent-to-treat analysis, 15% patients receiving standard
interferon/ribavirin (10 of 67 evaluable patients) had <100 copies/ml
HCV RNA; this compared to 44% of patients receiving Pegasys/ribavirin
(29 of 68 evaluable patients) who had undetectable (<100 copies/ml)
of HCV viral load (p=0.0003).
Patients with genotype 1: 33% (17/51) of patients receiving
Pegasys/RBV had undetectable HCV RNA vs 7% receiving standard IFN/RBV
Non-genotype 1 patients: 80% (Pegasys/RBV) vs 40% (IFN/RBV) (p=0.06).
About 50% of patients were able to normalize their ALT.
About one-third to half of the viral nonresponders had a biopsy at
week 24 and 26-40% had histologic improvement. This is very
encouraging, suggesting that a viral response may not be necessary to
see improvement in the liver of coinfected patients.
There were 17 grade 4 AEs in the Pegasys group vs 4 in the interferon
group, but the discontinuation rate was only 12% and it was the same
for both groups. Leukopenia (low white blood cell count) was reported
more often in the Pegasys arm but was successfully managed by dose
reduction or GCSF or both. Both treatment groups reported about equal
numbers of grade 2 and 3 adverse events.
Absolute CD4 counts declined by 80 (from 450 to 370) in the
interferon group by week 24, and by 120 in the Pegasys group (500 to
380). But the CD4% did not decline.
There was no apparent effect on HIV viral load during therapy. Some
patients who had undetectable HIV before starting HCV therapy became
detectable (5%-10%), but some patients with detectable HIV viral load
before HCV therapy became undetectable (10%-18%).
The predictors of viral response (by multivariate statistical
analysis) were: receiving Pegasys (p=0.004); white race (p=0.016);
Karnofsky score = 100 (p=0.046); fibrosis score 0-2 (out of 6)
Dr Chung emphasized that it is important to identify patients with
HCV early in their disease stage (early testing). This is underscored
by the better response to therapy for patients in this study with low
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