Treating Opportunistic Infections Among HIV
Download
Report
Transcript Treating Opportunistic Infections Among HIV
Guidelines for Prevention and Treatment
of Opportunistic Infections in HIV-Infected
Adults and Adolescents
Hepatitis C Virus Disease Slide Set
Prepared by the AETC National Resource Center
based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes in
either content or attribution. Users are asked to honor
this intent.
-AETC National Resource Center
http://www.aidsetc.org
2
May 2013
www.aidsetc.org
HCV Disease: Epidemiology
HCV disease is a leading non-AIDS cause of death
in HIV-infected persons
20-30% of HIV-infected U.S. patients have HCV
coinfection
HCV is a single-stranded RNA virus
7 genotypes
Genotype 1: ~75% of HCV infections in United States; ~90% of
HCV infections in U.S. blacks
3
May 2013
www.aidsetc.org
HCV Disease: Epidemiology (2)
Transmission: percutaneous exposure, sexual
exposure, perinatal, contaminated blood products
or medical equipment
Percutaneous transmission:
HCV is 10 times more infectious than HIV through
percutaneous blood exposures
Injection drug use is most common risk in the U.S. (via
syringes or injection paraphernalia)
HCV can survive for weeks in syringes
Other risks: intranasal cocaine use, tattoo placement
4
May 2013
www.aidsetc.org
HCV Disease: Epidemiology (3)
Sexual transmission
HIV appears to increase risk of sexual transmission of
HCV
In HIV-infected MSM, multiple outbreaks of acute HCV
Risk factors: unprotected receptive anal sex, sex toys,
recreational drug use, concurrent STD
In HIV-uninfected MSM, HCV transmission inefficient
Heterosexual transmission uncommon; increased risk if
partner is HIV/HCV coinfected
5
May 2013
www.aidsetc.org
HCV Disease: Epidemiology (4)
Perinatal transmission
HIV appears to increase transmission risk
HCV incidence:
1-3% if HCV-infected mothers had detectable plasma HCV
4-7% if mothers had detectable plasma HCV RNA
10-20% if mothers had HIV/HCV coinfection
6
May 2013
www.aidsetc.org
HCV Disease: Epidemiology (5)
HIV infection speeds progression of HCV to
cirrhosis, especially if CD4 count is <200 cells/µL
HIV speeds progression from cirrhosis to endstage liver disease (ESLD) and hepatocellular
carcinoma (HCC)
7
May 2013
www.aidsetc.org
HCV Disease: Clinical Manifestations
Acute hepatitis C:
Usually asymptomatic or mildly symptomatic;
usually not recognized
<20% have symptoms of acute hepatitis (eg,
fever, right upper quadrant pain, nausea,
vomiting, anorexia, jaundice)
Liver transaminases may be elevated
Recognizing possible acute HCV is important, given
greater efficacy of treatment in early HCV
8
May 2013
www.aidsetc.org
HCV Disease: Clinical Manifestations (2)
Chronic hepatitis C:
Often asymptomatic
Fatigue is common
With progression, stigmata of portal
hypertension (eg, spider angiomata, temporal
wasting, splenomegaly, caput medusa, ascites,
jaundice, pruritus, encephalopathy)
May see skin abnormalities (leukocytoclastic
vasculitis, porphyria cutanea tarda), renal
disease
9
May 2013
www.aidsetc.org
HCV Disease: Diagnosis
Screen all HIV-infected patients for HCV at
entry into care: sensitive immunoassay
For at-risk HCV uninfected, retest annually or as
indicated by risk exposure
To confirm infection: HCV RNA by sensitive
quantitative assay
HCV RNA does not correlate with HCV disease;
should not be monitored serially unless on HCV
treatment
HCV RNA correlated with likelihood of response to
HCV treatment
10
May 2013
www.aidsetc.org
HCV Disease: Diagnosis (2)
False-negative HCV antibody results are possible
in HIV- infected persons with advanced
immunosuppression (<1%)
Negative HCV antibody result can occur during
acute infection
Window period before seroconversion is 2-12 weeks
Test for HCV RNA if risk of HCV, high ALT, but negative
or indeterminate serologic test
11
May 2013
www.aidsetc.org
HCV Disease: Preventing Exposure
Encourage injection drug users to enter substance
abuse treatment program
Advise IDUs not to share needles or drug
preparation equipment if unable to stop using
Needle exchange may facilitate access to sterile
equipment
Inform patients of risks associated with nonsterile
body piercing, tattooing
Encourage safer sex, especially condom use, to
reduce sexual transmission of HCV
12
May 2013
www.aidsetc.org
HCV Disease: Preventing Disease
No vaccine or recommended postexposure
prophylaxis
After acute HCV, treatment within 6-12 months
may prevent chronic infection; high rates of HCV
clearance
Acutely infected patients should be offered treatment,
unless contraindications
Peginterferon (PegIFN) +/– ribavirin (RBV)
Some experts recommend observation for ~3-6
months to see if HCV will clear spontaneously
13
May 2013
www.aidsetc.org
HCV Disease: Preventing Disease
Prevent liver damage:
Avoid alcohol consumption
Avoid hepatotoxins; limit acetaminophen intake
(<2 g/day)
Avoid iron supplementation unless iron
deficiency
Vaccinate against HAV, HBV if nonimmune
If cirrhosis, consult with specialist
Serial screening for HCC:
Optimal strategy unknown; some recommend ultrasound
every 6-12 months
AFP has poor specificity and sensitivity; should not be used
as the only screening method
14
May 2013
www.aidsetc.org
HCV Disease: Preventing Disease (2)
Liver transplant is not absolutely contraindicated in
HIV/HCV coinfection
May refer coinfected patients with well-controlled HIV
and liver decompensation or early HCC
ART associated with reduced risk of liver disease
progression
Treat with ART in accordance with usual ART guidelines
Dosage adjustment of some ARVs may be needed for
patients with decompensated cirrhosis
15
May 2013
www.aidsetc.org
HCV Disease: Treatment
Goal of HCV therapy: sustained virologic
response (SVR), absence of detectable viremia
≥6 months after discontinuation of HCV
treatment
SVR associated with decreased risk of endstage liver disease, HCC, death; may decrease
risk of ARV-related liver injury
16
May 2013
www.aidsetc.org
HCV Disease: Treatment (2)
HCV treatment should be considered for all
HIV/HCV patients
Assessments before HCV treatment:
Genotype (GT): should be done before treatment
Important determinant of likelihood of response
to IFN-based treatment
GT 2 or 3 disease has higher rate of response
to treatment than do GT 1 or GT 4
For GT 1, subtype (A or B) also may influence
treatment response
HCV NS3/4A protease inhibitors (PIs) approved
for GT 1 treatment only
17
May 2013
www.aidsetc.org
HCV Disease: Treatment (3)
Assessments before HCV treatment (cont’d):
IL28B genotype
C/C genotype associated with better treatment
outcomes (vs C/T or T/T)
Utility and cost effectiveness uncertain
Liver disease stage
Baseline and serial ALT and AST: higher levels
predictive of faster liver disease progression
Cirrhosis can be present in persons with normal ALT
Liver biopsy: preferred test to evaluate disease stage,
exclude other causes, and guide treatment decisions
Not required before treatment
18
May 2013
www.aidsetc.org
HCV Disease: Treatment (4)
Treatment Regimens
PegIFN + ribavirin recommended backbone of
treatment for HIV/HCV-coinfected patients,
regardless of HCV genotype
For GT 1, limited clinical trial data in HIV/HCV
coinfection show HCV NS3/4A PIs (boceprevir,
telaprevir) + PegIFN/ribavirin have greater efficacy
than PegIFN/ribavirin alone
Recommended if not on ARVs with significant drug
interactions with HCV PIs
Note: Many new agents for treatment of HCV are in development;
some are expected to be available in the near future.
19
May 2013
www.aidsetc.org
HCV Disease: Treatment (5)
For chronic HCV, decision to treat should involve
assessment of potential risks and benefits of
current therapy
Medical urgency for treatment based largely on
degree of fibrosis; if minimal liver disease (no or
mild portal fibrosis), may consider deferring
therapy in anticipation of availability of new HCV
drugs
20
May 2013
www.aidsetc.org
HCV Disease: Treatment (6)
Factors that favor treatment initiation:
High likelihood of SVR
HCV GT 2 or 3
HCV GT 1 and low-level HCV RNA (<400,000 IU/mL)
HCV GT 1 and favorable IL-28B (C/C)
Medical necessity
Advanced fibrosis (bridging fibrosis or cirrhosis)
Vasculitis (owing to HCV)
Membranoproliferative glomerulonephritis (owing to HCV)
Patient with high motivation for treatment
Note: Many new agents for treatment of HCV are in development; future HCV
regimens may include options with greater efficacy and less toxicity.
21
May 2013
www.aidsetc.org
HCV Disease: Treatment (7)
Factors that favor treatment deferral:
Untreated HIV with advanced immunosuppression (CD4 <200
cells/µL)
Hepatic decompensation
Severe concurrent medical conditions
Severe uncontrolled psychiatric illness
Current alcohol or substance abuse
Hgb <10 g/dL, ANC <1000/µL, platelets <50,000/µL
Pregnancy or breast-feeding
Women who may become pregnant, and their male partners:
unwillingness to practice contraception during treatment and for 6
months afterward
Sarcoidosis
Uncontrolled autoimmune disease
Hemoglobinopathies
22
May 2013
www.aidsetc.org
HCV Disease: Treatment (8)
Acute HCV:
PegIFN-2a 180 mg SQ weekly, or PegIFN-2b
1.5 mcg/kg SQ weekly
Plus
Ribavirin:
GT 1: 600 mg PO BID if weight ≥75 kg
(600 mg QAM, 400 mg QPM if weight <75 kg)
GT 2, 3, 4, 5, 6: 400 mg BID
Duration: 24-48 weeks
HCV PIs should not be routinely used: high
SVR rates with standard therapy; no data for
HCV PIs in acute HCV
23
May 2013
www.aidsetc.org
HCV Disease: Treatment (9)
Chronic HCV, GT 1
PegIFN-2a 180 mg SQ weekly, or PegIFN-2b
1.5 mcg/kg SQ weekly x 48 weeks
Plus
Ribavirin 600 mg PO BID if weight ≥75 kg (600
mg QAM, 400 mg QPM if weight <75 kg) x 48
weeks
Plus/minus
An HCV PI (based on ART use)
If unable to access HCV PIs or DAAs and
treatment cannot be deferred: PegIFN +
ribavirin as above, x 48 weeks
24
May 2013
www.aidsetc.org
HCV Disease: Treatment (10)
Chronic HCV; GT 2, 3, 4, 5, or 6
PegIFN-2a 180 mg SQ weekly, or PegIFN-2b
1.5 mcg/kg SQ weekly
Plus
Ribavirin: 400 mg BID
Duration: 48 weeks (some recommend
response-guided therapy)
HCV PIs should not be used
25
May 2013
www.aidsetc.org
HCV Disease: Treatment (11)
HCV PI use with concomitant ART
ART
HCV PIs
No ART or
raltegravir + 2
NRTIs
• BOC 800 mg PO TID with food, beginning
after 4 weeks of PegIFN + ribavirin; continue
for 44 weeks
• TVR 750 mg PO TID with 20 g of fat, for 12
weeks (with PegIFN + ribavirin); continue
PegIFN + ribavirin for total of 48 weeks
Atazanavir/ritonavir • TVR 750 mg PO TID with 20 g of fat, for 12
+ 2 NRTIs
weeks (with PegIFN + ribavirin continued for
total of 48 weeks)
Efavirenz + 2
NRTIs
• TVR 1,125 mg PO TID with 20 g of fat, for 12
weeks (with PegIFN + ribavirin continued for
total of 48 weeks)
Abbreviations: BOC = boceprevir; TVR = telaprevir
26
May 2013
www.aidsetc.org
HCV Disease: Treatment (12)
HCV PI use with concomitant ART (cont’d)
ART
HCV PIs
Other ARVs
• Defer HCV treatment (especially if no or
minimal fibrosis)
• PegIFN + ribavirin without HCV PI if good
prognosis for treatment response (eg, IL28B
CC or low HCV RNA (<400,000 IU/mL)
• If feasible, modify ART to a regimen listed
above to allow use of BOC, or
• If complex ART history or resistance to multiple
classes of ART, consult with experts; TVR may
be preferred HCV PI because of shorter
duration of use
Abbreviations: BOC = boceprevir; TVR = telaprevir
27
May 2013
www.aidsetc.org
HCV Disease: Treatment (13)
If ribavirin is contraindicated:
PegIFN-2a 180 mg SQ weekly, or PegIFN-2b 1.5
mcg/kg SQ weekly
Likelihood of SVR without ribavirin is markedly lower
HCV PI should not be given without ribavirin (high risk
of virologic failure)
If decompensated liver disease
PegIFN is contraindicated
Liver transplantation if feasible
28
May 2013
www.aidsetc.org
HCV Disease: Starting ART
Optimal timing of ART initiation relative to HCV
treatment has not been established
HIV disease should be clinically stable (with or
without ART) before HCV therapy
HCV treatment responses may be better if
pretreatment CD4 count is higher
Most patients with CD4 <350 cells/µL on ART should
receive ART x ≥6 months before HCV treatment
HCV treatment not routinely recommended if CD4 <200
cells/µL
29
May 2013
www.aidsetc.org
HCV Disease: Starting ART (2)
Concurrent treatment of HIV and HCV may involve
complex medical regimens, high pill burdens,
potential drug-drug interactions, and increased
toxicities
AZT: should be avoided with PegIFN/ribavirin because
of higher rate of severe anemia
Didanosine: strictly contraindicated for use with
ribavirin--increased didanosine toxicity including lactic
acidosis
Abacavir: conflicting data re association with lower
likelihood of SVR; routine discontinuation is not
recommended
30
May 2013
www.aidsetc.org
HCV Disease: Starting ART (3)
Substantial risk of drug-drug interactions between
ARVs and HCV PIs (BOC and TVR)
PK and/or clinical data available for some but not all
ARVs
BOC can be given with raltegravir (PK data show
significant bidirectional interactions with PIs)
TVR can be given with efavirenz (with dose increase of
efavirenz), ritonavir-boosted atazanavir, and raltegravir
If feasible, change to acceptable ART regimen before
treatment with BOC or TVR
For patients with CD4 >500 cells/µL, some experts
recommend completion of HCV PI phase of HCV
treatment before ART initiation
31
May 2013
www.aidsetc.org
HCV Disease: Monitoring of Response to
Therapy
Treatment response is determined by HCV RNA
response; monitoring required before, during, and
after treatment
Treatment week 4: change in HCV RNA gives early
assessment of likelihood of SVR
With PegIFN/ribavirin:
If <1 log10 decrease, <5% probability of SVR
If undetectable HCV RNA (rapid virologic response, RVR), 80%
probability of SVR
With PegIFN/ribavirin + TVR, stop treatment if HCV RNA
>1,000 IU/mL
Treatment week 8
With PegIFN/ribavirin + BOC:
If undetectable HCV RNA (RVR), greater likelihood of SVR
32
May 2013
www.aidsetc.org
HCV Disease: Monitoring of Response to
Therapy (2)
Treatment week 12:
With PegIFN/ribavirin:
Null virologic response: If <2 log10 reduction from baseline:
discontinue PegIFN/ribavirin as sole treatment
Partial early virologic response (EVR): ≥2 log10 decrease but
detectable
Complete EVR: undetectable HCV RNA: 60-65% probability of
SVR
With PegIFN/ribavirin + TVR, stop treatment if HCV
RNA >1,000 IU/mL
With PegIFN/ribavirin + BOC, stop treatment if HCV
RNA >100 IU/mL
33
May 2013
www.aidsetc.org
HCV Disease: Monitoring of Response to
Therapy (3)
Treatment week 24:
With PegIFN/ribavirin:
For patients with partial EVR, retest at week 24; if undetectable
HCV RNA, 20% probability of SVR
For all treatment regimens (including those with BOC or
TPV), stop treatment if detectable HCV
End of treatment (week 24 or 48):
End of treatment response: undetectable HCV RNA
24 weeks posttreatment
SVR: undetectable HCV RNA
34
May 2013
www.aidsetc.org
HCV Disease: Adverse Events
PegIFN:
Side effects common; severity variable
“Flulike” symptoms (fever, myalgia, headache),
fatigue, nausea, alopecia, depression (may be
severe), insomnia, cognitive dysfunction,
cytopenias including reversible CD4 decrease,
retinopathy, neuropathy, autoimmune disorders,
hypo- or hyperthyroidism (monitor TSH),
ophthalmic complications
May limit dosage or limit ability to complete therapy
35
May 2013
www.aidsetc.org
HCV Disease: Adverse Events (2)
Ribavirin:
Hemolytic anemia, cough, dyspepsia
Anemia may limit dosage
Teratogenic; women with potential for
pregnancy and men receiving ribavirin must use
contraception consistently during ribavirin
therapy and for 6 months after completion of
therapy
36
May 2013
www.aidsetc.org
HCV Disease: Adverse Events (3)
Boceprevir:
Anemia, neutropenia, dysgeusia
37
May 2013
www.aidsetc.org
HCV Disease: Adverse Events (4)
Telaprevir:
Rash (up to 56% of patients, may be severe),
pruritus, anemia, nausea, vomiting, diarrhea,
anal discomfort or burning, hyperbilirubinemia
(with atazanavir-ritonavir coadministration)
Patients with rash should be followed for
progression, or development of systemic
symptoms (SJS and DRESS have been reported)
If severe rash or systemic symptoms, discontinue
TPV; if no improvement in 7 days, discontinue
PegIFN and ribavirin
If SJS or DRESS, stop all medications and refer
for urgent care
38
May 2013
www.aidsetc.org
HCV Disease: Adverse Events (5)
Monitor with clinical and laboratory exams before
treatment and at least monthly (more frequently
during the initial 12 weeks of HCV PI therapy)
Pretreatment:
CBC, electrolytes, creatinine, ALT, AST, albumin, total
bilirubin, TSH, HIV RNA, CD4, pregnancy test for
women of child-bearing potential
Depression screen
During treatment:
Monthly: clinical visits, CBC, electrolytes, creatinine,
ALT, AST, albumin, total bilirubin, pregnancy test,
depression screen
Every 3 months: HIV RNA, CD4, TSH
39
May 2013
www.aidsetc.org
HCV Disease: Adverse Events (6)
If cytopenias: manage with dosage reduction of
IFN (neutropenia, thrombocytopenia) and/or
ribavirin (anemia)
Growth factors if dosage reduction is not sufficient
If adverse neuropsychiatric effects:
antidepressants, other mood stabilizers
40
May 2013
www.aidsetc.org
HCV Disease: Treatment Failure
Limited data in HIV/HCV coinfected patients with
treatment failure; with PegIFN/ribavirin, SVR rates
generally markedly lower than for treatment-naive
patients
Retreatment of HCV GT 1 monoinfected patients with
HCV PIs + PegIFN/ribavirin: SVR depends on
previous virologic response
SVR rates higher if previous virologic relapse or partial
virologic response, lowest if null response
Retreatment of coinfected patients with HCV PIs: few
data
Evaluate carefully for need for retreatment; refer for
studies of investigational DAAs when possible
41
May 2013
www.aidsetc.org
HCV Disease: Preventing Recurrence
No protective immunity after infection; reinfection
possible if new exposure to HCV (eg, via injection
drug use or unprotected sex)
Patients who achieve SVR should be counseled
to avoid reinfection
Methods that prevent sexual transmission of HIV
should prevent sexual transmission of HCV
42
May 2013
www.aidsetc.org
HCV Disease: Considerations in
Pregnancy
All HIV-infected pregnant women should be
tested for HCV
Evaluation, including liver biopsy, can be
delayed ≥3 months after delivery
(pregnancy-related changes in HCV activity
should resolve)
Hepatitis A and hepatitis B vaccination can
be given; should be given if not immune
43
May 2013
www.aidsetc.org
HCV Disease: Considerations
in Pregnancy (2)
HCV treatment with PegIFN and ribavirin is
contraindicated during pregnancy
IFN: has antigrowth and antiproliferative effects; is
abortifacient in monkeys
Ribavirin: FDA category X; teratogenic at low dosages
in many animal species
Both women and men must be counseled about risks and
need for consistent and effective contraception during
ribavirin therapy and for 6 months after completion of therapy
BOC, TPV: pregnancy category B, but must be used
with IFN and ribavirin, which are contraindicated
44
May 2013
www.aidsetc.org
HCV Disease: Considerations in
Pregnancy (3)
Perinatal HCV transmission: higher risk for HIVcoinfected women
Limited data on efficacy of medical or surgical
preventive measures
Cesarean delivery does not decrease risk of perinatal
HCV transmission, and may increase risk of maternal
morbidity in HIV-infected women
Cesarean delivery in HIV/HCV-coinfected women can
be considered based on HIV-related indications; data
insufficient to support routine use for prevention of HCV
transmission
45
May 2013
www.aidsetc.org
Websites to Access the Guidelines
http://www.aidsetc.org
http://aidsinfo.nih.gov
46
May 2013
www.aidsetc.org
About This Slide Set
This presentation was prepared by Susa Coffey,
MD for the AETC National Resource Center in May
2013
See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
47
May 2013
www.aidsetc.org