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Ting Tan created on 2008-11
Epsom & St Helier’s Healthcare Trust
HIV and HCV Co-Infection
Treatment Guidelines 2008
(Ting Tan, Clinical Nurse Specialist, Dr S. Moodie & Dr A. G. Lim
Consultants Gastroenterology)
Contents
1.
2.
3.
4.
5.
6.
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8.
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10.
11.
12.
13.
14.
15.
16.
17.
Background
Patient Selection - Inclusion Criteria, Exclusion Criteria
Assessment & initial work-up
Drug interactions
When to start treatment
Treatment options
Length of treatment
Dosage
Treatment side-effects
Treatment response and discontinuation
Patient Monitoring
Post treatment monitoring
Dosage Modification Guidelines
Counselling patients (see mono infection protocol 2004)
General monitoring for patient who NOT on treatment
Algorithm-BHIVA
References
Appendices
1. Patient Information Sheet - Combination treatment
2. Liver histology scores
3. Patient Monitoring Sheets
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1.Background
Primary Goal of therapy(2)

Viral eradication (sustained viral response (SVR) defined as negative HCV PCR
RNA 6 months after end of treatment).
Secondary Goal of therapy(4)

Improvement of fibrosis and necroinflammation and decreasing the risk of
hepatotoxicity
2.Patient Selection:
(i).Inclusion Criteria

Similar to those in mono HCV infected patient 2004
Note: Ideally include information on histology obtained from liver biopsy, for
accurate assessment of the stage and severity of disease
However, due to high degree of success rate, Genotype 2 and 3 does not required
biopsy (1)

CD4 count > 200cells/mm³
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(ii)Exclusion Criteria

HIV RNA > 100,000 copies/mL – Patient to initiate High Active Antiviral
Therapy (HAART first, for minimum of 4-6 weeks before initiating HCV
treatment (2)

See mono HCV infected patient protocol 2004

HIV/HCV coinfection patient with decompensated liver disease. Referred patient
to transplant centre
3.(i)Assessment:

Clinical History

Family History of liver disease

Personal History
-
Any Intravenous Drug use
-
Previous and current alcohol intake
-
Psychiatric illness
-
Previous test for HCV
-
Any indication of possible time of first infection e.g.
jaundice, tattoing, piercings, major operations, blood
transfusions, date of first injected drug use

Sex with a HCV-positive partner
Examine the patient for clinical stigmata of chronic liver disease i.e. jaundice,
spider angiomata, palmar erythema, splenomegaly and caput medusa
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3.(ii)Initial work-up (1, 2)
1. HBsAg, anti-HBs
2. anti-HAV IgG
3. FBC
4. Clotiing Studies
5. Liver function tests (including albumin and GGT)
6. TFT
7. random glucose
8. prothrombin time
9. lipid profile
10. Serum Ferritin, serum iron and TIBC
11. Liver autoantibodies
12. Liver ultrasound
13. HCV Genotype and Viral load (note- if repeated exposure to HCV is
suspected, genotype may change over time, hence need to be measure again
later)
14. CD4 absolute counts and percentage
15. HIV RNA
16. Counselling including discussion of routes of transmission, complications of
disease, treatment options and advise regarding alcohol intake
17. Opthalmologic evaluation (1,2)
18. Mental assessment
4.Drug Interactions (1,2)

AZT/d4T

Didanosine (ddl) (10)

Stavudine/Zidovudine (10)
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Concurrent administration of drugs as listed increases the risk of anaemia (16,17),
increased mitochondrial toxicity such as pancreatitis and lactic acidosis (6,12,13),
spontaneous hepatic decompensation (14,15)
5..When to start treatment

HCV should be treated first if the HIV infection is stable and not requiring
treatment (11)

HIV should be treated prior to HCV if the CD4 count is low (CD4 count <200
cells/microL) (2) or patient deemed to be at risk of HIV progression

Patient stabilized on HAART and has been on the medications for minimum of 46 weeks (2)
6.Treatment Options
This treatment options and regime was drawn up in line with BHIVA(1) and UptoDate(2)
recommendations. Note, that these are based upon higher SVR rate (5,7)

Standard interferon is not recommended

Pegylated Interferon (PegIFN) alpha and Ribavirin
7.Length of Treatment

Pegylated Interferon and Ribavirin for 48 weeks for ALL Genotypes (1,2,5,6,7)

For Genotype 1 with slow declining HCV RNA levels, and advanced liver
disease, treat for additional 9 months after a non detectable viral load is achieved
if patient is tolerating treatment.(21)
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8.Dosage

As per mono HCV infected patient protocol 2004 (pg 9)

NOTE: Weight based Ribavirin (10.6mg/kg) for Genotype 1 and 4 (2,18,19,20)
9.Treatment side-effects

Approximately 0.5 log fall in HIV viral load (5)

Drop in absolute CD4 count

CD4 percentage not affected (7)

Opportunistic infections (5)

See per mono HCV infected patient protocol 2004
10.Treatment response and discontinuation

As per mono HCV infected patient protocol 2004

Note: In individual failing to achieve HCV RNA less than 50iu, or less than a 2
log drop in HCV RNA at 12 weeks, treatment is to continue if the aim is to
achieve histological improvement rather than HCV eradiction (1)
11. Patients monitoring during treatment

FBC every 1-2 weeks for 2 months

TFT quarterly

HIV RNA and CD4 counts and percentage every quarterly

Lipid every 6mths

HCV RNA at 12 weeks (4)

Others as per mono HCV infected patient protocol 2004
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12. Post treatment monitoring

Late relapse or re-infection may occur and individuals who undergo SVR should
have PCR performed yearly post successful therapy.
13.Dosage modifications guidelines

As per mono HCV infected patient protocol 2004

Use growth factors (eg Neupogen or erythropoietin) to avoid dose decrements
14.Counselling patients

see per mono HCV infected patient protocol 2004

CD4 counts may improve after stopping alcohol(9)
15.General monitoring for patients NOT ON treatment

Cirrhotic patients (2)
- Diagnostic imaging every 6 -12 months
- Serum alphfetoprotein every 6-12 months
- Endoscopy for presence of cirrhosis

Note:Liver Biopsy (2)
- Every 3 years if treatment deferred in fibrotic patients
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17.References
1.BHIVA Guidelines-HIV and Chronic Hepatitis (2004): Co infection with HIV and
Hepatitis C virus infection
2.McGovern, B.H. et al (2008) Management and treatment of hepatitis C in the HIVinfected patient, UptoDate (www.uptodate.com)
3.Kelleher, T.B. et al (2008) Management of treatment induced side effects for chronic
hepatitis C, UptoDate (www.uptodate.com)
4.McGovern, B.H. (2007) Hepatitis in the HIV-infected patient, Journal Acquired
Immune Deficiency Syndrome; 45 suppl 2:S47
5.Torrriani, F.J., M. Rodriguez-Torres, J.K. Rockstroh, et al (2004) The Apricot Trial:
Peg interferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in
HIV-infected patients, New England Journal of Medicine; 351:438
6.Carrat, F. F. Bani-Sadr, et al, (2004) The Ribavic trial: Pegylated interferon alfa-2b vs
standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV infected
patients: a randomized controlled trail; JAMA, 292:2839
7.Chung, R.T., J. Andersen et al (2004) The AIDS Clinical Trial Group (ACTG) 5071:
Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for
chronic hepatitis C in HIV-coinfected persons, New England Journal of
Medicine; 351:451
8.Nunez, M., A. Marino et al, (2007) The Presco trial; Baseline serum hepatitis C virus
(HCV) RNA level and response at week 4 are the best predictors of relapse after
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treatment with pegylated interferon plus ribavirin in HIV/HCV coinfected
patients, J Acquir Immnune Defic Syndr; 45:439
9.Pol. S., P. Artu, et al (1996) Improvement of CD4 cell count after alcohol withdrawal
in HIV-positive alcoholic patients, AIDS; 10: 1293
10.Brinkman, K., J.A. Smeitink et al (1999) Mitochondrial toxicity induced by
nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the
pathogenesis of antiretroviral-therapy-related lipodystrophy, Lancet; 354:1112
11.Soriano, V (2006) Treatment of chronic hepatitis C
individuals:selection of candidates, J Hepatology; 44:S44
in
HIV-positive
12.Sulkowaski, M.S., D.L.Thomas et al (2002) Hepatotoxicity associated with nevirapine
or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections,
Hepatology; 35:182
13.Vento, S., T. Garofano et al (1998) Enhancement of hepatitis C virus replication and
liver damage in HIV-coinfected patients on antiretroviral combination therapy,
AIDS; 12:116
14.Mauss, S., W.Valenti et al (2004) Risks factors for hepatic decompensation in patients
with HIV/HCV coinfection and liver cirrhosis during interferon-based therapy,
AIDS; 18:f21
15.Bani-Sadr, F., F. Carrat et al (2005) Spontaneous hepatic decompensation in patients
coinfected with HIV and hepatitis C virus during interferon-ribavirin combination
treatment, Clinical Infection Disease; 41:1806
16.Fuster, D., J.A. Gomez et al (2005) Short communication. Baseline factors associated
with haematological toxicity that leads to a dosage reduction of pegylated
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interferon-alpha2a and ribavirin in HIV-and HCV-coinfected patients on HCV
antiviral therapy,Antiviral Therapy;10:841
17.Brau, N, M. Rodriquez-Torres et al (2004) Treatment of chronic alpha-2b+ full course
vs 16-week delayed ribavirin, Hepatology; 39: 989
18.Manns, M., J. McHutchinson et al (2001) Peginterferon alfa-2b plus ribavirin
compared with interferon alfa-2b plus ribavirin for initial treatment of chronic
hepatitis C: a randomized trial, Lancet; 358:958
19.Fried, M.W., M.L. Shiffman et al (2002) Peginterferon alfa-2a plus ribavirin for
chronic hepatitis C virus infection, New England Journal Medicine; 347:975
20.Hadziyannis, S.J., H.Jr, Sette et al (2004) Peginterferon-alpha2a and ribavirin
combination therapy in chronic hepatitis C: a randomized study of treatment
duration and ribavirin dose, Annal Internal Medicine; 140:346
21.Drusano, G.L. & S.L.Preston (2004) A 48 week duration of therapy with pegylated
interferon alpha 2b plus ribavirin may be too short to maximize long term
response among patients infected with genotype-1 hepatitis C virus, J Infect Dis;
189:964
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