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become out of date quickly.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
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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
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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
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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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
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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.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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HCV Disease: Adverse Events (3)
Boceprevir:
 Anemia, neutropenia, dysgeusia
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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
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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
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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
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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
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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
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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
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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
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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
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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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
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