Optimizing Care for the

1
Optimizing Care for the HIV-Hepatitis
Coinfected Patient
Mark Holodniy, MD Professor of Medicine Stanford
University Stanford, California
Supported by an educational grant from Abbott
Sponsored by The Academy for Continued
Healthcare Learning
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Intended Audience This activity is intended for
HIV specialists from a wide range of disciplines,
including but not limited to internal medicine,
family practice, and infectious disease
physicians. Pharmacists, nurses and other
healthcare professionals focusing on HIV care are
also encouraged to attend. In accordance with
PhRMA guidelines, this program is intended for
healthcare professionals only. Activity
Purpose To update physicians, pharmacists,
nurses and other health care professionals, on
recent advances in HIV research and the
management of HIV infectious disease. Method of
Participation This activity will consist of a
lecture meeting with collateral slides, syllabus,
and interactive question and answer session.
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• Accreditation
• The Academy for Continued Healthcare
  Learning (ACHL) is accredited by the
• Accreditation Council for
  Continuing Medical Education (ACCME) to provide
  continuing medical education for physicians.
• Designation
• The Academy for Continued Healthcare
  Learning (ACHL) designates this
• educational activity for a
  maximum of 1.0 AMA PRA Category 1 CreditTM.
• Physicians should only claim
  credit commensurate with the extent of their
• participation in the activity.
• The Academy for Continued Healthcare
  Learning (ACHL) is accredited by the
• Accreditation Council for
  Pharmacy Education (ACPE) as a provider of
• continuing pharmacy education. In
  order to receive credit, pharmacists must
  complete the activity requirements and evaluation
  at the conclusion of the program. This activity
  has been approved for a maximum of 0.1 CEU.
• ACPE Universal Program Number
  (UPN) 396-000-06-013-L02
• Initial Release Date 01/20/06
• The Academy for Continued Healthcare Learning
  (ACHL) has been
• reviewed and approved as an
  Authorized Provider by the International
  Association of Continuing Education and Training
  (IACET). ACHL has awarded 0.1 CEU to participants
  who successfully complete this program. IACET
  CEU credit may be used toward nursing credits.
  Contact your local accrediting body for details.

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Disclosure Statements
The Academy for Continued Healthcare Learning
(ACHL) requires that the faculty participating in
a CME/CE activity disclose to the participant any
relevant affiliation or other financial
relationship (1) with the manufacturers of any
commercial product(s) and/or provider(s) of
commercial services discussed in an educational
presentation, and (2) with any commercial
supporters of the activity. The ACHL also
requires participating faculty to disclose when
unapproved/unlabeled uses of a product are
discussed in a CME/CE activity. Mark Holodniy,
MD, has no relevant affiliations or financial
relationships to disclose. The ACHL staff
members and others involved with the planning,
development, and review of the content for this
activity have no relevant affiliations or
financial relationships to disclose.  
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Disclaimer

• The content for this activity was developed
  independently of the commercial supporter. All
  materials are included with permission. The
  opinions expressed are those of the faculty and
  are not to be construed as those of the publisher
  or grantor.
• This educational activity was planned and
  produced in accordance with the ACCME Essential
  Areas and Elements, Policies, and Standards for
  Commercial Support as well as the ACPE Criteria
  for Quality and Interpretive Guidelines.
  Recommendations involving clinical medicine in a
  continuing medical education (CME/CE) activity
  must be based on evidence that is accepted within
  the profession of medicine as adequate
  justification for their indications and
  contraindications in the care of patients. All
  scientific research referred to, reported or used
  in CME/CE in support or justification of a
  patient care recommendation must conform to the
  generally accepted standards of experimental
  design, data collection and analysis.
• Participants are advised that one or more
  presentations in this CME/CE activity may contain
  references to unapproved or unlabeled uses of
  drugs or devices. Participants should note that
  the use of these agents outside current approved
  labeling is considered investigational and are
  advised to consult current prescribing
  information for these products.

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Housekeeping Information

• Please refer to the syllabus for complete CME/CE
  credit information
• Please return your completed enrollment/evaluation
  forms to the Meeting Host before you leave
• Please turn your cell phones to off or vibrate

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Learning Objectives

• Upon completion of this activity, participants
  should be able to
• Describe liver-related adverse events in
  HIV-Hepatitis coinfected patient
• Examine associated hepatotoxicity with different
  treatment modalities
• Review treatment options, taking into
  consideration hepatic safety

8
Liver-Related Adverse Events

• Liver-related adverse events are the most common
  grade 4 adverse events in HIV positive patients
• Hospitalizations for liver related events are
  more common than hospitalizations for
  opportunistic infections or for IDU related
  events
• Liver toxicity of ARV agents should be seriously
  considered before initiating therapy

9
Most Common Grade 4 EventsCPCRA Cohort
Liver 2.6
Incidence
Neutropenia 1.5
per 100 Person-Years
Anemia 1.1
CVD 0.9
Pancreatitis 0.9
Psychiatric 0.8
Renal 0.6
Hazard Ratio For Death by Grade 4 Event (95 CI)
3.49 (2.38-5.12) P.0001
1.02 (0.61-1.72) P.93
1.76 (0.99-3.09) P.051
7.08 (4.15-12.05) P.0001
3.40 (1.82-6.33) P.0001
1.91 (0.79-4.63) P.15
4.60 (2.45-8.66) P.0001
N2947 CPCRATerry Beirn Community Programs for
Clinical Research on AIDS.
Reisler RB, et al. JAIDS. 200334379-386.
10
Prevalence of HIV/HCV Coinfection
HIV/HCV Coinfection Prevalence by Risk Factor

• Johns Hopkins HIV clinic
• Urban setting
• Prospective, longitudinal database
• HCV-coinfection clinic established in 1997
• 1742 HIV-infected patients screened for HCV
  infection (1997-2000)
• HCV 798 patients

Prevalence of Antibody HCV,
IDU Hetero- Homo- Entire
sexual sexual Cohort
Sex Sex
Sulkowski MS, et al. Hepatology. 200032.
Abstract 204.
11
Impact of HIV Infection onHBV and HCV Disease
Progression
HBV or HCV Disease Course

• Impact of HIV infection
• Accelerates the course of HBV and HCV infection
• Liver disease associated with HBV or HCV
  infection
• A leading cause of morbidity and mortality among
  HIV-infected patients

HBV or HCV Infection
15
85
Chronic
Recovery
68
17
Cirrhosis
Stable
4
13
HCC ESLD
Slowly Progressive
Thomas DL, et al. JAMA. 2000284450-456.
Benhamou Y, et al. Hepatology.
1999301054-1058. Graham CS, et al. Clin Infect
Dis. 200133562-569. Bodsworth NJ, et al. J
Infect Dis. 19911631138-1140. Gilson RJ, et al.
AIDS. 199711597-606.
HCChepatocellular carcinoma.ESLDend-stage
liver disease.
12
Rapid Progression of Liver Disease in HIV/HCV
Coinfected Patients

• Prospective study of fibrosis progression in 67
  coinfected patients
• 2 biopsies, median time between biopsies was 2.84
  years

Patients With Mild Fibrosis (F1) on First Biopsy
gt25 of patients with mild fibrosis on initial
biopsy had 2 stage progression in fibrosis score
Change in Ishak Score From First to Second Biopsy
Sulkowski M, et al. 12th CROI. Boston. 2005. Oral
abstract 121.
13
Survival of Patients Coinfected WithHIV and
Hepatitis B or C Virus
HIV or Liver Mortality

• Cohort study
• 472 HIV patients followed for 8343 patient-months
• HIV alone (n126)
• HIV/HBV (n72)
• HIV/HCV (n256)
• HIV/HBV/HCV (n18)
• Variables associated with liver death in the
  cohort coinfected with HCV, HBV, or both (n346)
• 0 to 2 antiretroviral drugs
• CD4 lt200 cells/µL

Mortality,
HIV HIV/HBV HIV/HCV HIV
HBV/HCV
Bonacini M, et al. AIDS. 2004182039-2045.
14
Association Between CD4 Cell Count and
Liver-Related Death

• DAD Study
• Prospective study with 23 441 people with HIV
• 1248 deaths between 2000-February 2004
• Leading causes of death
• AIDS, 30
• Liver-related death 14 (79 associated with
  chronic hepatitis)
• Heart disease 9
• Non-AIDS malignancies, 8
• Relative risk of death for persons with CD4 lt50
  cells/mm3 as compared with persons with CD4 gt500
  cells/mm3

Weber, R, et al. 12th CROI. Boston. 2005.
Abstract 595.
15
HAART and the Impact of HIV RNA, CD4, or Both on
Liver Fibrosis
0.196
P.005
P.005
P.04
0.162
0.155
0.145
P.005
0.122
0.123
0.121
Ishak Fibrosis Units/Year
lt400 400-99K 100K
350 lt350 lt400
400
CD4 (cells/mm3)
HIV RNA (copies/mL)
HIV RNA (copies/mL) lt500 CD4 cells/mm3
Brau N, et al. 39th EASL. Berlin, 2004. Abstract
99.
16
HAART and Liver Fibrosis in HIV/HCV Coinfected
Patients

• HAART may slow fibrosis progression
• HIV/HCV coinfection versus HCV monoinfection
  post-HAART No difference in
• Fibrosis progression rate (P.29)
• Fibrosis stage (P.87)
• Necroinflammatory grade (P.89)
• Fibrosis progression rate (FPR) in Coinfected
  patients
• Strongly correlated with HIV RNA levels
• Coinfected patients with any HIV RNA gt400
  copies/mL had a faster FPR than coinfected
  patients with HIV RNA lt400 copies/mL (P.004)
• Coinfected patients with HIV RNA lt400 copies/mL
  had a similar FPR to HCV monoinfected patients
  (P.253)
• Increased with CD4 cell counts lt500 cells/mm3
  combined with HIV RNA gt400 copies/mL
  (P.005)

Brau N, et al. 39th EASL. Berlin, 2004. Abstract
99.
17
Impact of HAART and ART on Mortalityin HIV/HCV
Coinfected Patients

• Bonn cohort (1990-2002)
• 285 HIV/HCV coinfected patients
• Liver-related mortality rates per 100
  person-years
• HAART 0.45
• ART 0.69
• No therapy 1.70
• Predictors for liver-related mortality
• No HAART
• Low CD4 cell count
• Increasing age

Qurishi N, et al. Lancet. 20033621708-1713.
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Summary Clinical Implications of Liver Damage
and Benefits of HAART in Coinfected Patients

• Liver damage in HIV-infected patients causes
  significant morbidity and mortality
• HIV infection accelerates the course of viral
  hepatitis
• Patients with low CD4 cell counts have an
  increased risk of liver-related death
• HAART
• Can be tolerated by coinfected patients
• Controls HIV
• May slow the progression of fibrosis, especially
  PIs
• Improves immune status
• Improves survival

19
Balancing HAART and Hepatic Safety

• NRTIs

20
NRTI-Related Hepatotoxicity

• Syndrome of mitochondrial toxicity
• Mitochondria have their own DNA (mtDNA) that
  encodes 13 of mitochondrial proteins
• NRTIs inhibit mitochondrial DNA synthesis,
  causing mitochondrial dysfunction and cellular
  toxicity
• High-risk drugs
• Stavudine, didanosine, zalcitabine
• Low-risk drugs
• Abacavir, zidovudine, lamivudine

Fleischer R, et al. Clin Infect Dis.
200438e79-e80.
21
Association of Dideoxynucleoside Analogues With
Hepatic Steatosis

• Retrospective chart review of 179 HIV/HCV
  coinfected patients
• Univariate analysis
• Factors associated with steatosis
  Dideoxynucleosides (P.029) and the number of
  nucleoside analogues (P.042)
• Use of protease inhibitors was not associated
  with steatosis
• Multivariate analysis

McGovern B, et al. 12th CROI. Boston. 2005.
Abstract 950.
22
Balancing HAART and Hepatic Safety

• NNRTIs

23
NNRTI-Related Hepatotoxicity

• Incidence of ALT or AST elevations in randomized
  trials
• Grade 3 (gt5 x ULN) and 4 (gt10 x ULN) 8 to 16
• Hepatitis coinfection increases the risk of
  hepatotoxicity
• Nevirapine
• Fatal hepatic necrosis
• US FDA warning

Sulkowski MS, et al. Hepatology.
200235182-189. Reisler R, et al. 1st IAS
Conference. Buenos Aires, 2001. Abstract
43. Stern J, et al. JAIDS. 200334(suppl
1)S21-S33. Wit FW, et al. J Infect Dis.
200218623-31. van Leth F, et al. Lancet.
20043631253-1263. Gallant JE, et al. JAMA.
200429191-201.
24
Risk Factors for Severe, Life-Threatening
Hepatotoxicity With Nevirapine

• Women with CD4 cell counts gt250 cells/mm3
• Have a 12-fold higher risk versus women with lt250
  cells/mm3
• Can be fatal
• Greatest risk of severe and potentially fatal
  hepatic events often associated with rash
• Occurs in first 6 weeks of nevirapine therapy
• Close monitoring recommended. In some cases,
  hepatic injury progresses despite discontinuation
  of treatment
• Nevirapine should not be used for chronic therapy
  among women with CD4 gt250 cells/mm3 when other
  options exist

Viramune package insert. Ridgefield, CT
Boehringer Ingelheim Pharmaceuticals, Inc 2005.
25
Meta-Analysis of AACTG StudiesOdds Ratio of
Severe Hepatotoxicity

• Retrospective analysis of 21 AACTG studies
• 9003 patients
• Single and double NRTIs
• Triple regimens including NRTIs, NNRTIs, and PI
• Overall incidence
• Severe hepatotoxicity 10
• 23 discontinued due to severe hepatotoxicity
• Liver-related mortality 0.3
• NRTI-based regimen 0.46
• NNRTI or PI-based regimen 0.13

Grade 3 or 4 elevations (gt5 x ULN).
Reisler R, et al. 1st IAS Conference. Buenos
Aires. 2001. Abstract 43.
26
2NN Study Severe Hepatotoxicity in Patients
Receiving NNRTI-Based Regimens

• Treatment-naïve patients
• 1216 enrolled
• HBV coinfected 5.2
• HCV coinfected 9.5
• NNRTI d4T 3TC
• Nevirapine qd (400 mg)
• Nevirapine bid (200 mg)
• Efavirenz qd (600 mg)
• Nevirapine efavirenz qd (400
  800 mg)
• 2 nevirapine-attributed deaths
• Fulminant hepatitis, pancreatitis, renal failure
• Stevens-Johnson syndrome (recovered)
• Later developed septicemia due to a
  methicillin-resistant Staphylococcus aureus
  infection

Grade 3/4 Hepatotoxicity
13.6
9.1
8.3
Patients,
4.5
QD BID Efavirenz
Efavirenz (n220) (n387)
(n400) Nevirapine

(n209)
Nevirapine
van Leth F, et al. Lancet. 20043631253-1263.
27
Study 006 Patients WithHepatitis C and/or Hep B
Coinfection

• Seropositive for hepatitis B and C at study entry
• 137 patients treated with efavirenz-containing
  regimens
• 84 patients treated with indinavir 2 NRTIs
• Discontinuations due to liver or biliary system
  disorders were similar (2 to 3)

ALT and AST gt5 Times ULN
20
13
Patients ()
7
7
ALT AST
Sustiva package insert. Princeton, NJ
Bristol-Myers Squibb Company 2003.
28
Summary of NNRTIs and Hepatic Safety

• There appears to be a modest class effect of
  NNRTIs on abnormal liver enzyme levels
• Rate of serious clinical (symptomatic)
  hepatotoxicity, ALT and/or AST levels gt5 times
  ULN is relatively low
• May be significantly higher in patients
  coinfected with HBV or HCV
• Unique hepatic event associated with nevirapine
• Immune-mediated
• Associated with rash
• Occurs almost exclusively within the first 6
  weeks of nevirapine treatment

29
Balancing HAART and Hepatic Safety

• PIs

30
PI-Related Hepatotoxicity

• Incidence of ALT and/or AST elevations in
  registration trials
• Grade 3 (gt5 x ULN) and 4 (gt10 x ULN) 1 to 9
• Full-dose ritonavir
• Only PI identified as an independent risk factor
  for severe hepatic injury
• Boosting doses of ritonavir (200 mg/d)
• Not associated with significantly higher
  incidence of severe hepatotoxicity versus other
  PIs
• Less data on newer PIs
• Atazanavir or fosamprenavir

Sulkowski MS, et al. Clin Infect Dis.
200438(suppl 2)S90-S97.
31
Incidence and Risk Factors of HAART-Associated
Hepatotoxicity

• Retrospective cohort analysis (n560)
• Risk factors for grade 4 liver enzyme elevations
  (HR 95 CI)
• Female sex 2.8 1.3-5.8
• Baseline ALT levels (per 10 U/L increase) 1.05
  1.01-1.11
• Chronic HCV infection 5.0 2.3-10.7
• Chronic HBV infection 9.2 4.1-20.6
• Recent discontinuation of lamivudine 6.8
  2.1-22.7
• Recent start of nevirapine 9.6 3.2-28.3
• Recent start of full-dose ritonavir 4.9
  2.0-12.1
• No increased risk if ritonavir dose 200 mg bid

12-week period after start of drug. Patients
without NRTIs experience using first-line ARV
versus subsequent regimens.
Wit FW, et al. J Infect Dis. 200218623-31.
32
Hepatotoxicity Associated with PI-Based Regimens
Low-Dose Ritonavir Design

• Prospective study (n1161)
• Evaluate grade 3/4 AST/ALT elevations of PIs
• Median follow-up 211-365 days
• Baseline characteristics
• Age 37 years
• Male 73
• African American 77
• HCV 46
• HbsAg 10
• ALT 30 IU/L
• CD4 168 cells/mm3
• HIV RNA 4.7 log10 copies/mL

1st PI-Containing Regimen
Nelfinavir
Saquinavir/r
Indinavir/r
Indinavir
Lopinavir/r
median
Sulkowski MS, et al. Hepatology.
200338698A. Sulkowski MS, et al. AIDS.
2004182277-2284.
33
Risk Factors for PI-AssociatedDrug-Induced Liver
Injury

• No increased risk observed with lopinavir/r and
  nelfinavir
• Results consistent with data from the randomized
  control trial by Walmsley (Study 863)
• HIV/HCV-coinfected patients
• 84 had no drug-induced liver injury

Multivariate analysis
Sulkowski MS, et al. Hepatology.
200338698A. Sulkowski MS, et al. AIDS.
2004182277-2284.
34
Study 863 60-Week Safety of Lopinavir/r and
Nelfinavir by Hepatitis Status

• Hepatitis B/C-positive patients
• Patients with ALT/AST gt3x ULN were excluded at
  screening regardless of hepatitis status
• Lopinavir/r patients (n57) tended to have a
  lower incidence of grade 3/4 AST and ALT
  elevations compared with nelfinavir-treated
  patients (n68)
• AST lopinavir/r 4 versus nelfinavir 13
• ALT lopinavir/r 12 versus nelfinavir 17
• Similar incidence of discontinuations due to
  hepatic adverse events in both groups (4)
• No discontinuations due to elevated liver enzymes
  in either group
• No hepatic-related events resulted in death

Bernstein B, et al. 1st IAS Conference. Buenos
Aires. 2001. Abstract 525.
35
Study 863 Selected Adverse Events and Laboratory
Abnormalities
Plt.05 and Plt.001 vs hepatitis positive
Bernstein B, et al. 1st IAS Conference. Buenos
Aires. 2001. Abstract 525.
36
Study 863 Demographics of HIV/HCV Coinfected
Patients
All patients received lamivudine stavudine. HCV
Genotype 1 71 of patients.
Sherman KE, et al. 11th CROI. San Francisco.
2004. Abstract 811.
37
Study 863 HIV/HCV-Coinfected Patients CD4 Cell
Counts Through 48 Weeks
On-Treatment
234
Lopinavir/r d4T 3TC Nelfinavir d4T 3TC
184
CD4 Change From Baseline (cells/mm3)
P0.247
0 8
16 24 32
40 48 LPV/r (n29)

(n23)
(n20) Nelfinavir (n41)
(n34)

(n35)
Weeks
Sherman KE, et al. 11th CROI. San Francisco.
2004. Abstract 811.
38
Study 863 HIV/HCV-Coinfected Patients Time to
HIV RNA lt400 and lt50 Copies/mL
HIV RNA lt400 Copies/mL
HIV RNA lt50 Copies/mL
100 87
100 73
Lopinavir/r (n29) Nelfinavir (n41)
Patients,
Patients,
Lopinavir/r (n29) Nelfinavir (n41)
First evaluated at 24 weeks
P.274
P.308
Weeks
Weeks
All patients received lamivudine stavudine.
Sherman KE, et al. 11th CROI. San Francisco.
2004. Abstract 811.
39
Study 863 HIV/HCV-Coinfected PatientsMean ALT
Through 48 Weeks
On-Treatment


63

Mean ALT, IU/L
44
Lopinavir/r d4T 3TC Nelfinavir d4T 3TC
0 8
16 24 32
40 48 LPV/r (n29)

(n24)
(n21) Nelfinavir (n41)
(n37)

(n35)
Weeks
Plt.05 and Plt.01 vs LPV/r.
Sherman KE, et al. 11th CROI. San Francisco.
2004. Abstract 811.
40
Meta-Analysis of Lopinavir/Ritonavir Efficacy in
HIV/HCV Coinfected Patients

• 48-week exposure data from 8 clinical trials
• 819 adult HIV-infected patients
• Hepatitis positive 132 patients with HCV and/or
  HBV coinfection
• Hepatitis negative 687 patients
• 5-year exposure data from Study M97-720
• Lopinavir/ritonavir
• At least as safe as nelfinavir
• 6.9 to 12.8 experienced grade 3 ALT elevations
• Overall coinfected patients did have 3 to 4 fold
  higher risk of ALT and AST elevations versus
  those without hepatitis

da Silva, et al. 15th IAC. Bangkok, 2004.
Abstract MoPeB3285.
41
Meta-Analysis Virologic Outcomes With
Lopinavir/Ritonavir
All patients received lamivudine stavudine.
da Silva, et al. 15th IAC. Bangkok, 2004.
Abstract MoPeB3285.
42
Meta-Analysis Week 48 CD4 Cell Gain With
Lopinavir/Ritonavir by Hepatitis Status
All patients received lamivudine stavudine.
da Silva, et al. 15th IAC. Bangkok, 2004.
Abstract MoPeB3285.
43
Meta-Analysis Findings

• A higher percentage of HIV/HCV coinfected
  patients treated with lopinavir/ritonavir
  maintained HIV RNA levels lt400 and lt50 copies/mL
  compared with nelfinavir-treated patients
• Lopinavir/ritonavir appears at least as safe as
  nelfinavir in HIV/HCV coinfected patients
• A minority of patients (6.9 to 12.8)
  experienced grade 3 ALT elevations
• Lopinavir/ritonavir appears to be equally
  effective against HIV infection in HCV positive
  and negative patients

da Silva, et al. 15th IAC. Bangkok, 2004.
Abstract MoPeB3285.
44
Study 418 HIV RNA lt50 Copies/mL Through Week 48
by Baseline Hepatitis Status (ITT NCF)
Easterbrook P. et al. HIV7. Glasgow, UK. 2004.
Abstract 164.
45
Study 418 CD4 Count Mean Change From Baseline
by Baseline Hepatitis Status
Easterbrook P. et al. HIV7. Glasgow, UK. 2004.
Abstract 164.
46
Study 418 Incidence of Resistance Through Week 48
LPV/r 800/200 mg QD (n115)
LPV/r 400/100 mg BID (n75)
Patients eligible for resistance testing1
Genotypic results available Lopinavir
resistance2 Tenofovir resistance3 Emtricitabine
resistance4
11 8/11 0/8 0/8 2/8
11 7/11 0/7 0/7 1/7
1HIV RNA gt500 copies/mL any time during Weeks
12-24. All samples gt500 copies/mL were submitted
for testing 2LPV/r resistance emergence of
primary or active site mutation at protease
positions 8, 30, 32, 46, 47, 48, 50, 54, 82, 84,
90, with phenotypic LPV resistance FC gt 2.5 vs WT
3TDF resistance emergence of K65R or any TAM
(41, 67, 70, 210, 215, 219) in RT 4FTC
resistance emergence of M184V mutation in RT
Molina JM, et al. XV IAC. Bangkok, Thailand.
2004. Abstract WePe5701.
47
Summary of PIs and Hepatic Safety

• Rate of serious clinical (symptomatic)
  hepatotoxicity, ALT and/or AST levels gt5 times
  ULN is relatively low
• Boosting doses of ritonavir not associated with
  significantly higher incidence of severe
  hepatotoxicity versus other PIs
• Patients coinfected with HBV and/or HCV
• Greater risk of hepatotoxicity
• Lopinavir/ritonavir appears at least as safe as
  nelfinavir
• Boosted PIs can help suppress resistance to other
  ARV agents
• More data for atazanavir and fosamprenavir are
  needed in this patient population

48
Conclusions
49
Conclusions

• High prevalence of HIV-hepatitis coinfection
• HIV RNA and CD4 are correlated with fibrosis
  progression in coinfected patients
• Use of NNRTIs is associated with increased risk
  of hepatotoxicity
• For PI regimens, no increased risk if ritonavir
  dose lt200 mg bid

50
Conclusions, cont.

• Patients treated with boosted PIs tend to have a
  lower incidence of grade 3/4 AST and ALT
  elevations than patients treated with nelfinavir
• Boosted PIs tend to suppress HIV RNA better than
  nelfinavir in HIV/HCV coinfected patients
• Boosted PIs can help suppress resistance to other
  ARV agents (eg, tenofovir DF)

51
Recommended Regimens forTreatment-Naïve
Patients DHHS 2006
Preferred Regimens
Lopinavir/ritonavir (400/100 mg 2 tablets bid
or 800/200 mg 4 tablets qd) ZDV (3TC or
FTC)
Efavirenz (ZDV or TDF) (3TC or FTC)
Alternative Regimens
NNRTI-Based Efavirenz (3TC or FTC) (ABC or
ddI or d4T) Nevirapine (3TC or FTC) (ZDV or
d4T or ddI or ABC or TDF) Triple NRTI Abacavir
3TC ZDV (only when a preferred or an
alternative NNRTI- or PI-based regimen cannot or
should not be used)
PI-Based Atazanavir, fosamprenavir,
ritonavir-boosted fosamprenavir,
ritonavir-boosted indinavir, nelfinavir, or
ritonavir-boosted saquinavir All used in
conjunction with (3TC or FTC) (ZDV or d4T or
ABC or TDF or ddI) Lopinavir/ritonavir (3TC or
FTC) (d4T or ABC or TDF or ddI)
Not recommended for use in 1st trimester, or in
women with high pregnancy potential. Ritonavir
100 mg/day recommended when tenofovir DF is used
with atazanavir. Low-dose 100 to 400 mg/day as
a pharmacologic booster. Adult females and males
with CD4 cell counts lt250 and lt400 cells/mm3,
respectively. Soft-gel or hard gel capsules, or
tablets.
Available at http//aidsinfo.nih.gov/Default.aspx
.
52
Post PresentationCME/CE Information

• Please return the completed enrollment/evaluation
  forms to the Meeting Host before you leave
• Certificate will be mailed to you within 6 weeks
• Please refer to the syllabus for complete
  accreditation information
• Inquiries/concerns may be directed to the CME
  Administrator at [phone], ext. 114

53
Thank You!
54
Case 1- HCV Diagnosis in HIV Infected Patient

• 43 y/o WM, unemployed, h/o IDU, found to be HIV
  positive last year. No f/u until today when he
  presents to clinic for evaluation
• You obtain labs and determine that his CD4 count
  is 227 (14), HIV VL 84,000, Hemoglobin 13, ALT
  51 and HCV Ab, HBV sAg are negative. No current
  meds.
• Given his HIV VL and CD4 count ARV Rx is
  recommended.
• In your consideration about ARV regimens in this
  patient, you discuss potential liver toxicity.
• Despite negative hepatitis serologies is any
  further or repeat testing warranted?

55
Case 2- HIV Treatment in the HIV/HCV Coinfected
Patient

• 37 y/o AAF was diagnosed with HIV/HCV about 4
  years ago. Remote h/o IDU and minimal ETOH
  intake. Has ongoing depression. Works as a
  medical assistant. Current meds are Zoloft and as
  needed ibuprofen.
• Current Labs today HCV VL 7.1M genotype 1b, Chol
  220 (LDL 131), ALT 51
• CD4 count has been in the 400s, HIV VL 12,000,
  but over the last couple of years has drifted
  down to 300 (17) and the HIV VL is now 47,500.
• What type of ARV regimen would you consider using
  in this patient?

56
Case 3- HCV Treatment in the HIV/HCV Coinfected
Patient

• 51 y/o HM with HIV/HCV for over 10 years.
  Intermittently employed as a house painter. H/o
  HTN, smoker, on ARV Rx (Sustiva, Truvada) with an
  undetectable HIV VL and CD4 count 451 (21). His
  BMI is 29. Other labs include HCV VL 27.5M
  genotype 1a, ALT 67, Chol 247 (LDL 185), TG 97
• Liver biopsy 2 years ago showed grade 2 fibrosis
  and no cirrhosis.
• Although adherent to meds, he has missed a few
  appointments.
• Is this patient a candidate for HCV Treatment?
  What factors go into your decision?