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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