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Hepatitis B/C coinfection in women living with HIV Women for Positive Action is an educational program funded by AbbVie Contents Introduction Epidemiology of coinfection Risk factors for coinfection in women Coinfection outcomes: HIV/HCV coinfection Coinfection outcomes: HIV/HBV coinfection Coinfection in pregnancy Management of coinfection in women Under-representation of women in coinfection research Improving the care of women with coinfection Case study Introduction Women for Positive Action is an educational program funded by AbbVie An overview of Hepatitis C (HCV) HCV is a liver disease caused by the hepatitis C virus • The virus can cause both acute and chronic hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness • The incubation period for HCV is 2 weeks to 6 months Those who are acutely symptomatic may exhibit: 8 in 10 people remain asymptomatic after acute infection fever fatigue appetite jaundice nausea vomiting dark urine grey faeces joint pain abdominal pain WHO, 2014 An overview of Hepatitis C (HCV) 15–45% of people clear the virus naturally from their blood during the acute stage 55–85% of people will develop chronic infection Chronic HCV primarily affects the liver, with potential complications including chronic liver inflammation, liver cirrhosis and liver cancer The risk of cirrhosis of the liver is 15–30% within 20 years WHO, 2014 HCV: A worldwide epidemic Prevalence of HCV infection ˃3.0% 2.0%–2.9% 1.0%–1.9% <1.0% 130–150 million people globally have chronic HCV infection2 Not studied 1. Negro & Alberti, 2011; 2. WHO, 2014 HCV genotype distribution1,2 Types 1a and 1b account for about 60% of global infections3 1. Messina, 2015; 2. 3. WHO, 2014 An overview of Hepatitis B (HBV) HBV is a viral infection that attacks the liver and can cause both acute and chronic disease Most people do not experience any symptoms during the acute infection phase In those that do, symptoms can last several weeks: jaundice nausea fatigue dark urine vomiting abdominal pain In some people, chronic infection can cause chronic liver disease and increases risk of death from cirrhosis of the liver and liver cancer HBV vaccination is 95% effective in preventing infection and its chronic consequences WHO, 2014 Risk of chronic HBV infection depends on age at infection 80–90% of infants infected during the first year of life develop chronic infections 30–50% of children infected before the age of 6 years develop chronic infections <5% of otherwise healthy adults who contract HBV will develop chronic infection WHO, 2014 HBV prevalence Prevalence of HBV surface antigen ≥8.0% 5.0%–7.0% 2.0%–4.0% <2.0% Not studied >780,000 people die every year due to the acute or chronic consequences of HBV2 1. Ott, 2012; 2. WHO, 2014 The prevalence of HBV genotypes varies geographically HBV can be classified into eight genotypes (A to H)1–3 • Studies to date suggest that HBV genotypes/subgenotypes have important influences on the outcomes of chronic HBV infection3 • Genotype A is found mainly in Northern Europe, North America, and Africa3 Genotype B and C are prevalent in Asia3 Genotype E is found in West Africa and in small areas in the US, Vietnam and Southern Europe3 Genotype D is more common in Southern Europe, the Middle East and India3 Genotypes F and H are found in indigenous populations in Alaska and Central and South America3 Genotype G is found in Europe and the US4 Some studies suggest that genotype G is associated with a more severe liver fibrosis5 1. Lindh, 1997; 2. Norder, 1993; 3. McMahon, 2009; 4. Kato, 2001; 5. Lacombe, 2006 Hepatitis delta virus and superinfection • Superinfection is the hepatitis delta virus (HDV) infection of an individual chronically infected with HBV1 • HDV does not have the ability to replicate itself • Most patients with superinfection develop a progressive form of chronic hepatitis1 • Superinfection is often seen as a worsening clinical illness in an individual with previously stable chronic HBV1 • • Clinical illness with superinfection can be rapidly progressive The mortality rate for HDV infections lies between 2% and 20%2 • ten times higher than for hepatitis B 1. Negro, 2014; 2. Available at: http://web.stanford.edu/group/virus/delta/2005/ Common transmission routes for Hepatitis B and C Transmission route Hepatitis B Hepatitis C Intra-institutional (needle-stick injuries, contaminated medical equipment, tattooing) IV drug use Transfusion Haemodialysis Sexual Oral-oral contact X Household (e.g. razor, toothbrush) Mother-to-newborn Common Was common but now rare Infrequent X Never Adapted from: http://www.epidemic.org/thefacts/hepatitisc/transmission/ Epidemiology of coinfection Women for Positive Action is an educational program funded by AbbVie HIV and HCV coinfection Because of shared routes of transmission, HIV and HCV coinfection is frequent1 5 million individuals are estimated to be coinfected2 25–30% of people with HIV have HCV 1–12% of MSM2 Up to 95% of IDU2 9–27% of heterosexuals2 IDU, intravenous drug user; MSM, men who have sex with men 3 Although the risk of contracting HCV through sexual transmission is extremely low4, in recent years an active epidemic in MSM with highly risky sexual behaviour has been identified in several cities in the USA, Canada and Europe5 Implications for onward transmission to women? 1. Sulkowski, 2003; 2. Operskalski, 2011; 3. Alter, 2006; 4. Bradshaw, 2013; 5. van de Laar, 2007 HIV and HCV coinfection in women Women are more likely than men to report high-risk injecting behaviours, especially in the context of sexual and injecting relationships1 Among women reporting no history of IDU, women living with HIV are almost twice as likely as HIV-uninfected women to acquire HCV2 In a European study, 12% of pregnant women with HIV were coinfected3 Sex with a male IDU is independently associated with HCV2 IDU, intravenous drug user 1. Tracy, 2014; 2. Frederick, 2009; 3. Landes, 2008 HIV and HBV coinfection HIV and HBV have common routes of transmission and endemic areas, but HBV is more infectious1 ~100x 2–4 million 6–14% people with HIV are estimated to have chronic HBV infection2 people with HIV from Western Europe and the USA have chronic HBV infection overall2 In some settings, up to two-thirds of all people with HIV have a blood marker of past or present HBV infection1 9–17% of MSM2 7–10% of IDU2 4–6% of heterosexuals2 IDU, intravenous drug user; MSM, men who have sex with men 1. WHO, 2011; 2. Alter, 2006 HIV and HBV coinfection in women There is very little information on the prevalence of coinfection in women in general The prevalence of coinfection in pregnant women is 4–5%1–4 Women with HIV appear to have a lower level of viral activity than their male counterparts5 Higher proportion of men with advanced liver diseases compared to women (male:female ratio ~2.4)5 1. Landes, 2008; 2. Chikwuiekwu, 2014; 3. Eke, 2011; 4. Pirillo, 2007; 5. Jobarteh, 2010 Risk factors for coinfection in women Women for Positive Action is an educational program funded by AbbVie Risk factors for HCV coinfection Alcohol misuse1 Sharing straws used to snort drugs3 History of imprisonment2 IDU1 Risky sexual behaviour4,5 Violent sex5 Increased risk of HCV Use of ‘new’ drugs that require more frequent injection6 IDU, intravenous drug user 1. Simon, 2014; 2. Zahedi, 2014; 3. Aidsmap, 2008; 4. Frederick, 2009; 5. Taylor, 2012; 6. Aidsmap, 2013 Risky or traumatic sexual behaviour in non-IDU women puts them at risk of HCV • • Unprotected intercourse with IDU1 Unprotected intercourse with a coinfected partner2 • Those with HIV are less likely to spontaneously clear HCV, and their HCV RNA set point tends to be higher2 • More infectious to partners than HCV monoinfected individuals3 • Coinfected men are more likely than HIV-negative men to shed HCV RNA in semen4 • Unprotected intercourse that can be associated with mucosal trauma and bleeding2 • Anal intercourse, traumatic sexual practices, rape IDU, intravenous drug user 1. Frederick, 2009; 2. Taylor, 2012; 3. Sherman, 2005; 4. Briat, 2005 Risk factors for HBV coinfection Lower nadir CD4 T-cell count1 Heterosexual intercourse2 IDU1 Alcohol misuse1 Increased risk of HBV Postmenopause3 IDU, intravenous drug user 1. HIVandHepatitis.com, 2011; 2. Odunukwe, 2011; 3. Baig, 2009 The social context of drug use puts female IDUs at greater risk of coinfection Relationship • Women more frequently use drugs with individuals with whom with injecting they have a relationship, usually a sex partner partner Social network • Female IDUs' social networks tend to have more “hard drug” users and IDUs than male IDUs' networks Control over drug use • Women's access to drugs, injection paraphernalia, and other resources are often controlled or determined by their sex partners and/or others within their social network IDU, intravenous drug user Wagner, 2013 Prevention of coinfection in women with HIV Counselling on behaviour modification1 HBV vaccination4 Support for IDUs1-3 • Advice • Support • Recommended • Avoid • Advice • Response on safer personal care and sexual behaviours sharing toothbrushes, razors, limit number of sexual partners, use condoms • Support to stop or limit alcohol use HBsAg, hepatitis B surface antigen; antiHBs, anti hepatitis B surface antibody IDUs to start substance abuse treatment on use of sterile syringes and equipment • Needle exchange programmes • Interventions that focus on the mechanisms of cross-contamination to assist young IDUs in making educated decisions in all HIV patients who are negative for HBsAg and antiHBs to the vaccine varies - rates are ~25% in those with CD4-cell counts <200 cells/mm • In patients where HIV treatment is indicated ART should be initiated prior to HBV vaccination • Household and sexual contacts to HBV infected persons should also be offered vaccination 1. CDC, 2002; 2. Wagner, 2013; 3. Thomas, 2011; 4. WHO, 2011 Coinfection outcomes HIV/HCV coinfection Women for Positive Action is an educational program funded by AbbVie Impact of HIV on HCV outcomes • Lower rates of spontaneous HCV clearance • Only ~15–20% of individuals will clear acute HCV infection1 • Higher HCV viral loads, regardless of genotype2 • HCV progresses to cirrhosis >3x faster3 • Liver fibrosis is as advanced as in HIV-negative individuals who are 9.2 years older4 • Women with coinfection experience greater neurocognitive impairment than women with HCV alone5 1. Thomas, 2000; 2. Sherman, 1993; 3. Soto, 1997; 4. Kirk, 2013; 5. Giesbrecht, 2014 Impact of HCV on HIV outcomes (I) • • Survival is markedly lower in HCV/HIV coinfected individuals1,2 Liver disease is now the second leading cause of death among persons with HIV taking antiretroviral therapy1 (Age, years) Danish HIV Cohort Study, 2000-2005 data1 1. Thomas, 2011; 2 Lohse, 2007 Impact of HCV on HIV outcomes (II) • Evidence for the impact of HCV on HIV disease progression is conflicting • Large meta-analysis (30 studies and >100,000 individuals) • HCV increases the risk of overall mortality, but has little or no effect on immunological, virological or HIV-related clinical disease progression1 • Women’s Interagency HIV Study (WIHS) • Almost two-fold increased AIDS risk among coinfected women who never had a CD4 count <200 cells/μL or were ART-naïve2 • These findings suggest the need for earlier and more aggressive HIV and HCV treatment in coinfected individuals 1. Chen, 2009; 2. Kovaks, 2010 Impact of HCV on HIV outcomes (III) • High levels of t-cell activation are reported in coinfected individuals vs. those with HIV alone1 • Compared to those living with HIV alone, coinfected individuals have: >3x the risk of liver disease and liver failure2 Up to 9x the risk of liver-related death from HCV3 Increased risk of all-cause hospitalisation and hospitalisation for non-AIDS-defining infections4 1. Kovaks, 2010; 2. CDC, March 2014 3. Rockstroh, 2013; 4. Crowell, 2014 Gender differences in HCV coinfection outcomes: Disease outcomes There are a number of gender differences in the course of HCV coinfection1 Women experience a slower progression to cirrhosis and are less likely than men to develop hepatocellular carcinoma2 Women are twice as likely as men to spontaneously clear HCV without treatment3 Coinfection is associated with reduced bone mineral density (BMD) in women5 Onset of menopause is associated with the progression of liver disease, exposing women to a sudden worsening of their liver condition2,4 Alcohol overuse results in more deleterious effects in women6 Coinfected women may experience a greater level of psychiatric challenges compared to men1 Mortality rates may be higher in women vs. men1 1. Emery, 2010; 2. Burton, 2013; 3. Grebely, 2014; 4. Nasta, 2011; 5. Lawson-Ayayi, 2013; 6. Collazos, 2011 Impact of HCV coinfection on treatment • Individuals with HCV coinfection are more likely to be1-4: • ARV-naïve at recruitment than those with HIV infection only • Less likely to start ART subsequently • At increased risk of discontinuing ongoing regimens • Coinfected individuals are half as likely to respond to the same dose and duration of peginterferon and ribavirin therapy compared with those with just HCV5,6 • Initiation of ART is associated with increased risk of hepatotoxicity in individuals with coinfection7 • Data suggest that HIV/HCV-coinfected patients treated with new, alloral HCV regimens have SVR rates comparable to those of HCVmonoinfected patients 1. Sulkowski, 2002; 2. Cooper, 2006; 3. Rockstroh, 2005; 4. Mocroft, 2005; 5. Torriani, 2004; 6. Hadzivannis, 2004; 7. Nunez, 2010; 8. DHHS Guidelines 2014 Gender differences in HCV coinfection outcomes: Treatment outcomes Compared with coinfected men, coinfected women… …have a lower response to HAART (CD4 cell response)1 …experience some sideeffects of HCV treatment more frequently or more severely, thus requiring dose modification or treatment interruption2 … are significantly more likely to interrupt HIV treatment due to neuropsychiatric symptoms3 1. Palepu, 2006; 2. Bhattacharya, 2010; 3. Emery, 2010 Emotional and psychological impact of coinfection on women Dual stigma of HIV and HCV1,2 Women with HIV are at high risk of depression3 – exacerbated by coinfection and treatment1 Addition of HCV treatment to an already complex HIV regimen can be highly discouraging and emotionally challenging1 In IDUs withdrawal from illicit drug use and following a complex treatment regimen may lead to refusal to participate and non-adherence1 For some, especially young women, failure to respond to treatment can lead to self-blame, severe depression or misplaced rage1 IDU, intravenous drug user 1. Thomas, 2011; 2. Lekas, 2011; 3. Ickovics, 2001 Coinfection outcomes HIV/HBV coinfection Women for Positive Action is an educational program funded by AbbVie Impact of HIV on HBV outcomes • Reduced likelihood of spontaneous recovery from HBV infection1-6 • Increased progression to1-6: • • • • • Chronic disease Cirrhosis and its complications HBV sero-reversion HBV reactivation Occult B infection • Risk of death is 11x greater for coinfected individuals than those with HIV alone3 • Patients receiving HBV therapy have7: • Increased risk of hepatotoxicity when commencing HAART • Increased risk of hepatic flares when active treatment for both HIV and HBV is interrupted 1. Martin-Carbonero, 2001; 2. Bica, 2001; 3. Thio, 2002; 4. Bonacini, 2004; 5. Salmon-Ceron, 2005; 6. Thio, 2009; 7. WHO, 2011 Impact of HBV on HIV outcomes HBV status does not appear to have a significant impact on HIV virologic outcomes1 HOWEVER compared with individuals with HIV only, it has been shown to be related to: Significantly increased risk of AIDS/mortality1 Increased risk of all-cause hospitalisation and hospitalisation for non-AIDSdefining infections2 Impaired CD4cell recovery during ART3 1. Chun, 2014; 2. Crowell, 2014; 3. Wandeler, 2013 Gender differences in HBV outcomes • Very limited data are available on outcomes in HIV/HBV coinfection • In terms of HBV infection alone a systematic review reported that1: • Men are more likely to develop chronic HBV infection • Among those with HBV, the rate of clinical outcomes in terms of hepatocellular carcinoma (HCC), cirrhosis and mortality were consistently several fold higher in men than women • Most studies reported at least a two- to three-fold difference Taylor, 2009 Coinfection in pregnancy Women for Positive Action is an educational program funded by AbbVie HCV coinfection in pregnancy Prevalence of HCV coinfection in pregnant women in Europe is ~12%1 IDU history, maternal age and area of birth are independent risk factors for HCV coinfection in pregnancy1 HIV/HCV coinfection increases risk of vertical transmission of both HCV and HIV2 Around 1 in 10 children born to women living with coinfection have HCV3 IDU, intravenous drug user More than twice the rate of those born to women with HCV alone3 Coinfected women are twice as likely to have detectable HIV in the 3rd trimester/ delivery as women with HIV only1 1. Landes, 2008; 2. OHTN, 2010; 3. Benova, 2014 Pregnancy and breast-feeding in HIV/HCV coinfection Women of childbearing age should be educated about the risk of perinatal HCV transmission and any potential teratogenicity of treatment regimens1 Increased risk of MTCT reported in those with HIV/HCV coinfection1 Women with advanced disease are at increase risk of complications during pregnancy e.g. gestational diabetes, low birth weight and neonatal intensive care unit admission1 MTCT occurs in ~5% of cases where the mother is infected with HCV; evidence exists for both in utero and transvaginal transmission1 Cracked, bleeding or traumatised nipples could increase exposure of the infant to HCV. In this case the CDC propose temporary interruption of breast feeding1 Although HCV RNA has been detected in breast milk, breast-feeding does not appear to be a primary route of MTCT for HCV1 1. Burton, 2013 HBV coinfection in pregnancy There is no evidence of increased mother-to-child HBV transmission in coinfection over monoinfection1 • Compared with pregnant women without HIV, coinfected women are2: • 3x as likely to test positive for HBV DNA • 2x as likely to test positive for HBeAg (a signal of chronic infection) • Even with appropriate vaccination, 5–15% of infants born to mothers who test positive for HBV contract the disease3 • Up to 39% in women with high HBV DNA levels – often seen in HIV • Pregnant women with HBV coinfection have a higher risk of mild hepatoxicity • May lead to decreased initiation or discontinuation of ART4 1. BHIVA, 2012; 2. Hoffman, 2007; 3. Kourtis, 2012; 4. Andreotti, 2014 Management of coinfection in women Women for Positive Action is an educational program funded by AbbVie Supporting patients by providing education and support At screening, provide information on:1,2 • What is HCV • Transmission and risk reduction • Diagnosis • Vaccination After diagnosis, provide information on:1,2 • Reduction or stopping alcohol use • Drug use and risk reduction • Risks and benefits of treatment • Use of alternative therapies • Nutrition • Concurrent treatment of HIV and hepatitis When considering treatment, provide information on:1,2 • • • • Existing and new treatments Managing side effects Potential interactions with other medications Deferring treatments • Follow-up and development of a treatment plan • Emotional wellbeing and peer support • Chances of success or failure When undergoing treatment, provide information on:1,2 • Managing side effects • Follow-up and treatment efficacy • Adherence • Monitoring for drug interactions and toxicities • Ongoing monitoring of psychological and neurocognitive challenges 1. DHHS, 2006; 2. BHIVA, 2013 Regional HIV and hepatitis coinfection guidelines • A number of guidelines are available • However, apart from pregnancy, these are non-specific to gender and typically based on data extrapolated from predominantly male clinical trials Region HCV USA • AASLD/IDSA/IAS Guidelines, 20141 • AASLD Guidelines, 20092 • DHHS HIV Guidelines, 20143 • DHHS HIV Guidelines, 20114 • EACS HIV Guidelines, 2013*6 • EASL HCV Guidelines, 20147 • EACS HIV Guidelines, 2013*6 • EASL HBV Guidelines, 20118 • WHO Guidelines, 2011*9 Europe HBV Pregnancy • DHHS Guidelines for pregnant women with HIV, 2014*5 *HIV guidelines including a section on coinfection 1. AASLD/IDSA. HCV, 2014; 2. AASLD. HBV, 2009; 3. DHHS HCV/HIV, 2014; 4. DHHS HBV/HIV, 2011; 5. DHHS, 2014; 6. EACS, 2013; 7. EASL, 2014; 8. EASL, 2012; 9. WHO, 2011; 10. BHIVA, 2013. Local HIV and hepatitis coinfection guidelines Country UK HCV HBV • BHIVA Coinfection Guidelines, 20131 • BHIVA Coinfection Guidelines, 20131 Pregnancy • BHIVA HIV Guidelines in pregnancy, 2012*2 German • Deutsch-Österrreichische Leitlinie zur. HIV-Therapie in der Schwangerschaft und bei HIV-exponierten Neugeborenen3 • Aktuelle Empfehlung zur Therapie der chronischen Hepatitis C4 Spanish • Manejo de las hepatitis virales en pacientes infectados por el VIH Guía de Práctica Clínica de GeSIDA5 French • Prise en charge médicale des personnes vivant avec les VIH6 *HIV guidelines including a section on coinfection 1. BHIVA, 2013; 2. BHIVA, 2012; 3. German Guidelines, 2014; 4. German HCV Guidelines; 5. Spanish Guidelines, 2014; 6. French Guidelines, 2014. Screening All women with HIV should be screened for HCV and HBV at diagnosis and annually thereafter1–5 All pregnant women with HIV should be screened during pregnancy for HBV or HCV unless they are already known to be coinfected6 1. BHIVA, 2013; 2. EACS, 2013; 3. DHHS, 2014a; 4. WHO, 2011; 5. BHIVA, 2012; 6. DHHS, 2014b Diagnosis of HCV infection • Based on the detection of HCV RNA by a sensitive molecular method Acute infection • Since there is no serological marker, which proves that HCV infection is in the acute phase • the diagnosis of acute hepatitis C can only be confidently if seroconversion to anti-HCV antibodies can be documented Chronic infection • Detection of both HCV antibodies and HCV RNA in the presence of signs of chronic hepatitis, either by elevated aminotransferases or by histology EASL, 2014 HCV: A rapidly evolving treatment arena • HCV treatment requires a combination of drugs1 • Historically a combination of peg-IFN and ribavarin was the gold standard for HIV/HCV coinfection2 • Treatment uptake was very low, mostly due to the fear of high adverse event rates including a high rate of comorbid medical and psychiatric conditions • Subsequently protease inhibitors, telaprevir and boceprevir, were developed for use in combination with peg-IFN and ribavarin2 • Ongoing research has established a number of newer direct antiviral treatments e.g. sofosbuvir, daclatasvir or simeprevir1,2 • Decreased drug interactions and adverse events • A high success rate (SVR rates of >90% for 12 weeks of treatment) • Not necessary to combine with peg-IFN and ribavarin SVR, sustained virologic response 1. Petty, 2014; 2. Rockstroh, 2013 A large number of therapies are under investigation for the management of HCV Protease inhibitors •Telaprevir •Boceprevir •Simeprevir •Asunaprevir •Vaniprevir •Paritaprevir •Grazoprevir NS5A inhibitors •Daclatasvir •Ledipasvir •Ombitasvir •GS-5816 •Elbasvir Polymerase inhibitors NI’s •Sofosbuvir •Mericitabine NNI’s •Dasabuvir •Beclabuvir •ABT-072 Multi-class combination drugs Sofosbuvir + ledipasvir (Ombitasvir + paritaprevir + ritonavir) + dasabuvir Ombitasvir + paritaprevir + ritonavir Asunaprevir + daclatasvir + BMS791325 Grazoprevir + elbasvir Approved (as of February 2015) treatments are listed in red www.hepmag.com (last accessed 5 Jan 2015) EASL recommendations for treatment of HIV/HCV coinfection • • Indications for HCV treatment in HIV/HCV coinfected patients are identical to those who are monoinfected The same treatment regimens can be used, however the following combinations should be avoided due to drugdrug interactions • In those with HIV receiving simeprevir avoid: EFV, DLV, ETR, NVP, ritonavir, any PI/r • Daily daclatasvir dose should be adjusted to 30 mg and 90 mg daily in those receiving ATZ/r or EFV, respectively • No drug-drug interactions reported between sofosbuvir and ART EASL recommend collaborative clinical management including the hepatologist, the HIV physician, and the pharmacist EASL, 2014 Recommended assessments in those being treated for chronic HCV • Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy • The following laboratory tests are recommended within 12 weeks prior to starting antiviral therapy: • Complete blood count (CBC); international normalized ratio (INR) • Hepatic function panel (albumin, total and direct bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels) • Thyroid-stimulating hormone (TSH) if IFN is used • Calculated glomerular filtration rate (GFR) • The following laboratory testing is recommended at any time prior to starting antiviral therapy: • HCV genotype and subtype • Quantitative HCV viral load, except in the circumstance that a quantitative viral load will influence duration of therapy Patient warehousing • ‘Warehousing’ describes the phenomenon where physicians delay therapy until availability of newer more advanced treatment options which may offer a more favourable response to patients • Physicians should discuss warehousing with patients, giving special consideration to those with: • Advanced disease for which there is no therapy available • Mild-to-moderate disease c • Contraindications to IFN or those who failed triple therapy • The decision to defer treatment should be made jointly between physicians and patients, and based on: • Risk-benefit • Lifestage and risk of fibrosis progression • Pros and cons of current and future treatment options Peg-IFN, pegylated interferon Alberti, 2014 HCV treatment arena summary • Very active research and development with numerous new treatments in the pipeline and rapidly evolving developments in the area1–3 • In addition to clinical management EASL recommend focussing on service provision through dealing with challenges around1 • Patient warehousing • Accumulation of difficult-to-treat patients (e.g. those with liver or renal failure and coinfection • Access to treatment and availability of a range of DAA regimens • The latest EASL guidelines state that they cover drugs approved by EMA before the end of 20141 • AASLD/IDSA/IAS–USA HCV guidance is to be regarded as a regularly updated ‘living document’2 DAA, direct-acting antivirals 1. EASL, 2014; 2. Petty, 2014; 3. AASLD/IDSA. HCV, 2014 HBV vaccination in HIV • Vaccinate against HBV in those with no evidence of immunity or prior infection1,2,3 • HIV-positive individuals tend to have lower response rates and durability to vaccination4 • While immunocompetent individuals respond to HBV vaccination at rates >90%, those with HIV are reported to respond at rates of just 24–56%4 • If immunity is not achieved, revaccination using a double dose is advised1–3 • Although vaccination is important, patients need to be educated on transmission risks and avoidance of risky behaviours4 1. EACS, 2013; 2. BHIVA, 2013; 3. Mast, 2005; 4. Petty, 2014 EACS guidelines for the management of HIV/HBV coinfection • • • Screen all HIV+ individuals for HBV Screen for HDV antibodies in all HBsAg+ individuals Those with HIV/HBV coinfection benefit from early ART • liver fibrosis progression is reduced with immune reconstitution and suppression of HIV viral load • ART initiation with a TDF-based regimen is recommended • • • in all persons needing anti-HBV therapy irrespective of CD4 cell count in all HBsAg positive persons with <500 CD4 cells irrespective of disease status Stopping anti-HBV containing ART should be avoided in persons with HIV/HBV co-infection because of the high risk of severe hepatitis flares and decompensation following HBV reactivation hepatitis EACS, 2014 Emotional status in those with coinfection • • Higher levels of depression reported in coinfected patients vs those with HIV alone Coinfected individuals are more likely to experience emotional distress if they have lower levels of independence and spirituality ~ In many cases spirituality can often provide a positive channel for those faced with a long-term illness • Complexity of treatment plans and perceived risk of side effects can also increase emotional burden • The planning and implementation of tailored interventions is an important part of care Pereira, 2014 Counselling and support • Many women balance work and family commitments • The burden of side-effects can upset this balance • Counselling and emotional and practical support is recommended before and during treatment1,2 • Successful care programs offer counselling and education, beginning at the initial screening3 • Counselling and education must be an ongoing part of care, regardless of whether treatment is initiated3 1. HCV Advocate, 2014; 2. EASL HCV Guidelines, 2014; 3. TAG, 2006 Treating emotional health problems to improve health outcomes • Improve QOL1 Emotional health services Specialist education Patient education and peer support QOL, quality of life • Improve access to psychological services1 • Reduce stigma1 • Reduce distrust1 • Improve medication adherence1 • Reduce risky behaviour1 Whetten, 2008 Under-representation of women in coinfection research Women for Positive Action is an educational program funded by AbbVie Women remain under-represented in research into coinfection • • Gender differences in coinfection are largely unexplored1 and women are underrepresented in new studies3 A review by the OHTN highlighted that there is limited evidence specifically addressing the treatment, care, and support needs and gaps for HIV/HCV co-infected women4 OHTN , Ontario HIV Treatment Network Guidance from the NIH Office of Research on Women’s Health states2: ‘If gender differences have been shown to affect the course or impact of a treatment in early phases of research, then subsequent studies can be designed so that application of the treatment will benefit both men and women’ 1. Emery, 2010; 2. NIH, National Institute on Drug Abuse 2011; 3. Natap, 2013; 4. OHTN, 2010 Improving the care of women with coinfection Women for Positive Action is an educational program funded by AbbVie Access to care for coinfected patients • Improved treatment options for HCV are costly, posing a challenge for access to care ~ In resource-poor nations, HCV treatment will likely remain difficult ~ In developed nations, HCV may become a disease of those with difficult access to care and those more difficult to treat e.g. homeless, active IDUs, alcoholics and illegal immigrants • Awareness and advocacy is an important part of therapy to help improve treatment access to all those who require it Petty, 2014 Cost of therapy impacts on treatment access • • It is recommended that efforts be made to reduce costs and provide universal access in all HCV patients, independent of the severity of liver damage Assessment of the price of a course of therapy considers: ~ ~ ~ ~ ~ The cost of drugs The effectiveness of the treatment strategy Direct and indirect costs of the management of side-effects Impact of treatment on the natural history of the disease Impact of treatment on the costs of managing the disease over time Petta, 2015 Strategies to improve the care of women with coinfection: Healthcare professionals • Increase education to reduce misperception about treatment efficacy, necessity, feasibility and suitability for treatment • Establish a multidisciplinary team approach for the care of coinfected women • Ensure all women are screened for HCV/HBV on HIV diagnosis and offer universal referral for HCV care irrespective of perception of treatment candidacy • Encourage coinfected women to enter clinical trials to help determine gender differences in treatment Taylor, 2012 Strategies to improve the care of women with coinfection: Peer support groups • Improve knowledge using evidence-based and validated educational materials that are culturally sensitive and tailored to education/literacy levels • Improve motivation and mood through attendance at peer support groups; encourage initiation of peer-support groups based on learnings from similar experiences in HIV • Develop and implement evidence-based strategies to optimise treatment adherence e.g. reminder strategies such as mobile phone reminders • Enhance opportunities for integrated care, involving expert patients to optimise support Taylor, 2012 Initiatives to support women with or at risk of coinfection Women for Positive Action is an educational program funded by AbbVie iBASE: ‘Guide to hepatitis C for people living with HIV’ • Available for free download from the iBASE website http://i-base.info/guides/wp-content/uploads/2013/11/HIV-and-HCV-coinfection-Nov2013e.pdf Hepatitis/HIV Project • • Collaborates with activists, community members, scientists, governments and drug companies to make safer, more effective and less toxic treatment for viral hepatitis available The Project forges coalitions with activists worldwide to demand universal access care and treatment The priorities of people living with HIV and hepatitis are acted on All co-infected people have access to safe and effective treatment The Hepatitis/HIV Project aims to ensure: Availability of accurate and timely information on prevention, care and treatment Research on hepatitis is efficient, relevant and well-designed http://www.treatmentactiongroup.org/hcv/description Project inform • Offers information, inspiration and advocacy for people with HIV/AIDS and hepatitis C • Resources available include: “A Toolkit for Screening, Counseling and Patient Education: Hepatitis C Infection and People Living with HIV” ~ Includes materials for medical providers and other health care staff as well as patient fact sheets ~ Available for download on the website http://www.projectinform.org/hcvtoolkit/ REDUCE project • Aims to: ~ Understand the knowledge around transmission of HCV and the risk behaviours associated with HCV among female drug users ~ Develop and test an evidence-based group intervention to reduce HCV risk taking behaviours and increase HCV transmission knowledge among female IDU ~ Develop a support manual http://thereduceproject.imim.es/ Coinfection peer support groups Case study 1 Women for Positive Action is an educational program funded by AbbVie Case study: HIV/HCV coinfection • Coinfected woman with von willebrand syndrome ~ 42 years old • Contracted HIV/HCV coinfection in the early 1980s ~ Contaminated blood • Diagnosed with HIV/HCV coinfection 32 years ago ~ Receiving treatment for HIV ~ Undetectable viral load • Has previous tried older HCV therapies ~ Currently considering treatment with a newer DAA What challenges should be considered when initiating HCV treatment, as well as managing ongoing HIV treatment? Issues to consider Mental health and emotional wellbeing • Women with HIV are more likely to be diagnosed with mental health and emotional challenges than men • In addition, depression and anxiety are commonly observed in HCV • Coinfected women experience greater neurocognitive impairment than women with HCV alone • The challenges of forming lasting relationships, disclosure and the double stigma of HIV and HCV infection ~ Lack of awareness about HCV, how it is contracted and associated risks ~ Support may be required in forming lasting relationships and disclosure • Consider referral for counselling to provide emotional and practical support before and during treatment • Provide information on peer support groups Issues to consider Access to treatment • Newer treatment options for HCV are now available ~ However, pricing may be a limiting factor for treatment access in some countries • WHO recommend that national governments, international agencies, donors, civil-society organisations, and the pharmaceutical industry work together to help assure that HCV treatment is affordable and accessible for all those who need treatment • Organisations offering research and providing recommendations on access to treatment, include: Issues to consider Treatment choice, side effects and adherence • • • • Consider when therapy should be initiated - should she wait for the availability of newer regimens? If an older regimen is tried first what are the effects of potential treatment failure? Traditional HCV treatments are associated with a wide range of severe side effects Newer regimens have a better tolerability profile Consider the impact on adherence when adding another treatment to an already complex regimen • Women may need extra support and planning in this area, especially if there are practical or psychosocial issues that may impact adversely on adherence • Provide counselling and practical support around side effects both before and during treatment • Encourage patients to attend all clinic appointments to ensure appropriate monitoring • Support patients to adhere to the full course of treatment Case study 2 Women for Positive Action is an educational program funded by AbbVie Case study: HIV/HCV coinfection • IDU woman living with HIV ~ 25 years old • Diagnosed with HIV 6 years ago ~ Transmitted from partner at the time • • Received counselling and support to help cope with HIV diagnosis Recently diagnosed with HCV ~ Contracted through shared needles • Currently considering HCV treatment What challenges should be considered when initiating HCV treatment, as well as managing ongoing HIV treatment? Issues to consider Neurological and psychiatric challenges • Coinfected IDUs are more likely to experience psychiatric and neurological complications including cognitive impairment • There is also a risk of depression due to drug dependency and the chaotic lifestyle that is often associated with drug use • Coinfected women experience greater neurocognitive impairment than women with HCV alone • Provide advice of coping with the double-stigma of HIV/HCV coinfection • Consider referral for counselling • Offer monitoring of neurocognitive changes and referral to relevant teams as required • Provide information on peer support groups Issues to consider Adherence and continued care • Consider the impact on adherence in IDUs who may lead an unpredictable lifestyle • Accessing and maintaining care for HIV and HCV among drug users presents special challenges and the multidisciplinary team involved in care require • • • • a nonjudgmental attitude patience experience in the area Women may need extra support and planning with adherence • Highlight the importance of adherence for treatment success • Offer patients support to break the cycle of IDU and make changes to improve their lifestyle e.g. training, employment, housing, financial support options Issues to consider Treatment choice and drug-drug interactions • • • • Consider interactions between antiretroviral drugs and medications used for the treatment of drug addiction Consider the impact of treatment in a women who is an IDU with a chaotic lifestyle Offer education and suggestions on safe IDU practices Consider any potential drug-drug interactions with contraception and pregnancy including the impact on MTCT • Discuss the risk of drug-drug interactions between ART, HCV treatment and addiction treatment • Offer education and suggestions on safe IDU practices Thank you for your attention Any questions? Women for Positive Action is an educational program funded by AbbVie