HCV/HIVCo-infection A case study by Dominic Côté, Nurse Clinician B.Sc Chronic Viral Illness Services McGill University Health Centre
Objectives By sharing a case study of a patient co-infected with HIV/HCV we will : Get a better knowledge of the impacts of HIV infection on the course of Hepatitis C Be able to discuss the impacts and efficacy of new treatments against Hepatitis C on co-infected patients. Identify the issues of hepatitis C treatment that the healthcare team is facing
Introduction HIV co-infection negatively affects HCV disease progression: Decreased rates of spontaneous clearance in those with existing HIV : only 10% clear acute infection Higher HCV loads, regardless of genotype Impacts of treatment response to Pegylated interferon and Ribavirin dual combination regimens.
Introduction HIV co-infection negatively affects HCV disease progression: Faster progression to cirrhosis in individuals with untreated HIV infection Management of HIV infection requires consideration of : Effects of ART on HCV disease progression Optimizing ART regimen selection : Risk of hepatotoxicity Potential effects on fibrosis progression (control of HIV viremia may lead to slower rates of fibrosis progression) Drug-drug interactions with HCV therapeutic agents
Sometimes we forget Frank is 46 yo, HIV + since 1991, works at the McGill University faculty. His weight is 95kg Risk factor : MSM. No History of i/v drug use He was seen in our clinic Sept 2012 Past history of depression History of cardiac anomaly for which he was operated at 16yo; WPW / Post ablation a-fib Tricuspid regurgitation and pulmonary hypertension HCV diagnosed in 1998, but no further analysis.
But all the signs were there Frank was seen by an hepatologist for gastro-intestinal bleed : gastroscopy shows no varices, but mild portal gastropathy hypertension. Had a depression in the past and has fully recovered since Presented gum bleed On the doctor s visit : tricuspid murmur, liver is hard and has a presence of splenomegaly. No jaundice or edema, ascites and encephalopathy. Lab tests show: AST 95; ALT 101; Bilirubin 24.3; INR 1.13; albumin 38; platelets 57000; hemoglobin 143; WBC 3.50
Investigation for HCV Genotype 1a HCV RNA : 2,951,209 IU/ml (6.47 log) IL-28b: CT/TG Abdominal Ultrasound : normal liver, mild splenomegaly Fibroscan : 21.5 KPa Non immune for HBV and Hep A
Frank s HIV history HIV + since 1991, MSM. Involved in a serodiscordant relationship. HIV treatment history : 1998 : AZT/ 3TC/ Invirase never became undetectable; CD4 were low (110 cells/ul) August 2004 : Tenofovir/ 3TC/ Kaletra Became HIV undetectable 2 months later April 2009 : Truvada/ Kaletra stays undetectable and his CD4 increased at 390 cells/ul
Frank also takes other medications On Metropolol, Furosemid and Omeprazole.
So, overall Frank is co-infected HIV-HCV Obviously cirrhotic with stable, but low platelets count Has never been treated against HCV before Doesn t have the easiest profile : G1a, HCV V/L high and presenting cirrhosis. Has Hx of depression Now his HIV is well controlled but has been exposed to few ARV s and is currently taking Kaletra
What do you think? Should we treat his HCV? Could we wait? If we treat him : What treatment should we use? Should we make some changes to his HIV therapy / if so, for which one? What are the risks and what are our responsibilities as nurses?
What did we decide? We will treat Frank with Peg/IFN Ribavirin and Incivek (Telaprevir) But before we start the therapy we will have to : modify his HIV regimen to decrease the possibilities of drug-drug interactions make some changes to other medication that Frank takes get a psychiatric evaluation to assess his psychological state.
Why Incivek? Reduces chances of drug-drug interaction Incivek is less likely to have interactions with some ARV s It will give better chances to keep the patient s HIV disease well-controlled It will facilitate the adherence of the patient on the therapy because of Incivek s duration
Web site for interaction
What about Frank Frank met with our pharmacists Because the patient had very good response in the past with this ARV regimen : It was decided for now to D/C Kaletra and to replace it by Atazanavir and Ritonavir As per the psychiatrist, a low dose of citalopram was added for the patient's history of depression We also changed Omeprazole for Ranitidine, to again, avoid interaction (for reflux) Citalopram is the best choice of anti-depressant when there s Incivek s use, because of the low risk of drug-drug interactions.
Algorithm for Frank s treatment Which one should be used? A) B) Response-guided therapy algorithm for telaprevir. Adapted from Shiffman ML, et al. Liver Int. 2012;32:54-60.[9]
2 weeks before we start We wanted to make sure Frank was tolerating his new ARV regimen well. We did a TDM testing (treatment dose monitoring) also to make sure that levels of medication were therapeutic. We also completed the teaching for the HCV therapy.
Here an example of TDM
Finally the big Day happens Frank started the therapy with : Peg interferon Alpha 2b 150mcg weekly Ribavirin 1200 mg QD Telaprevir 750 mg TID 1st IFN injection is given
After 4 weeks, how is Frank doing? Good news, Frank is already HCV PCR negative. Platelet levels lowered at 35 000. Hgb stable at 137. Liver enzymes back to normal. Very good adherence to the treatment, no missed doses. HIV V/L undetectable and CD4 count 369 cells/ul What are his side effects for now : some flu-like symptoms post IFN inj, more irritable, cries easily, decreased energy and increased fatigue, anal burn and itchiness, dry skin but no rash encouraged to apply skin cream, anti-hemorroidal and zinc creams prescribed. We ll reassess patient weekly for now, especially because of the psychological effects.
After 8 weeks of therapy Frank is surviving! Has increased fatigue, but still able to work full time. Emotionally stable; mentions being more irritable and sad. Platelets again decreased : 25000. No bleeding. Hgb stable 118. Anal region better. No Rash. It was decided to decrease the IFN at 135mcg weekly, to increase also Citalopram at 20mg QD and to continue assessment every week.
What s going on at week 11 Feels emotionally much better. Less stressed. Still tired but eats well. Platelets level stable again at 38000. But Frank is yellow : bilirubin very high at 124. And according to the TDM, the Atazanavir (ATV) level is over therapeutic. We kept same IFN dose but discontinued Ritonavir to continue ATV at 300 mg QD.
At week 12 Yea Telaprevir is finished! HIV V/L undetectable and CD4 : 246 cells/ul HCV PCR still negative. HGB lower at 99. Bilirubin hasn t changed much, now 115. No improvement of jaundice. Otherwise no new side effects, but extreme fatigue, problems staying focused at work. Missing lots of days at work. Ribavirin dose is decreased at 1000mg QD and, patient is given papers to go off work. Again reassessment weekly.
Week 16. Frank is still yellow Physically and mentally stable. No new side effects. But bilirubin again very high : 116. Consult with our pharmacist Recommends changing the ARV regimen because of interactions with the HCV therapy. Atazanavir is stopped. Truvada is continued and Darunavir is started.
What happened then? Pt s bilirubin came back to normal after only 1 week. TDM test was done and ARV levels are therapeutic. Patient's HCV PCR has stayed negative for the treatment duration, but IFN dose had to be decreased from 120 mcg at week 27 to 105 mcg weekly at week 35 because of recurrent decrease of platelet levels.
Finally Frank passed through the treatment, but not without any difficulties. He lost a total of 10kg. With the decreased interferon dose, we are hoping he will have a SVR 3 months. We found the good HIV regimen to keep Frank undetectable and to limit a significant decrease in his CD4 count.
February 3rd 2014 Already 3 months post HCV therapy. HCV PCR negative 1 month post treatment. Frank is doing very well. His Hgb is now back to normal and his platelet level is higher than before the therapy. He recuperated almost 100% of his physical state and now back to work full time. Still on Citalopram and has same ARV s for now. Do you think Frank has good chances of SVR 3 months?
Conclusion There are risks of many interactions between DAA and ARV, and with the medications prescribed by other doctors. And most of these interactions haven t been studied yet. We know that it could be a challenge to treat patients that are co-infected with HIV and HCV, particularly when the ART was already administered, with an aeging population and with the management of co-morbidities.
Conclusion What should we do for better chances of success with our co-infected population? We need to get as much information as possible about our patient. HIV genotyping, tropism, past history, medical condition, psycho-social assessment, Fibroscan, pharmacological profile. HIV Viral load should be undetectable for at least 3 months and CD4 count higher than 300 cells/ul.
Conclusion We need to minimize and take care of drug-drug interactions by : Making sure the medication list is up to date Making sure to involve the pharmacist to evaluate the possible med interactions and to choose the right regimen. Using the treatment dose monitoring (TDM) to administer the therapeutic ARV dose during the HCV therapy.
Conclusion It is important to assess the patient s state regularly: side effects, laboratories We need to be available for the patient
Conclusion We know that adding DAA s for treatment of HCV in people co-infected with HIV substantially improves SVR. Several studies are underway and include co-infection. The results are promising. For now we should treat those who need it most and can t wait (cirrhotic people). But we must understand that they represent a challenge to the success and safety of their therapy.
Thank you. Questions?