Changing Landscape of Changing Landscape of Hepatitis C Management in 2011: Hepatitis C Management in 2011: Focus on HIV/HCV Co-InfectionFocus on HIV/HCV Co-Infection

Jay Kostman, MDJay Kostman, MDDivision of Infectious DiseasesDivision of Infectious Diseases

Viral Hepatitis CenterViral Hepatitis CenterPerelman School of Medicine of the Perelman School of Medicine of the

University of PennsylvaniaUniversity of Pennsylvania

HCV Genotype Distribution – U.S.HCV Genotype Distribution – U.S.

HIV CoinfectionHIV Coinfection22

AACTG Cross-Sectional AnalysisAACTG Cross-Sectional Analysis(n=66)(n=66)

General PopulationGeneral Population11

NHANES IIINHANES III(n=250)(n=250)

174%

2 15%

37%

4 1%

6 3%

183%

39%

4 2%

1Alter MJ et al. N Engl J Med 1999;341:556-562.2Sherman KE et al. Clin Infect Dis 2002;34:831-837.

26%

Sources of Infection for PersonsSources of Infection for Personswith Newly Diagnosed HCVwith Newly Diagnosed HCV

Injection drug use, 60%Injection drug use, 60%

Sexual, 15%Sexual, 15%Transfusion, 10%Transfusion, 10%

(before 7/1992)(before 7/1992)

Other, 5%Other, 5%• OccupationalOccupational• HemodialysisHemodialysis• Mother-infantMother-infant

Source: Centers for Disease Control and PreventionSource: Centers for Disease Control and Prevention

Unknown, 10%Unknown, 10%

Goals of HCV TherapyGoals of HCV Therapy

Pearlman BL, Traub N. Pearlman BL, Traub N. Clin Infect DisClin Infect Dis 2011;52:889-900. 2011;52:889-900.

Target Virus

Target Disease

Prevent Complications

Eradication (Viral Cure)

Delay Cirrhosis

Prevent Hepatocellular

Carcinoma

Natural History of HCV InfectionNatural History of HCV Infection

AcuteAcuteHCVHCV

ChronicChronicHCVHCV

HepaticHepaticInflammationInflammation

HepaticHepaticFibrosisFibrosis

CirrhosisCirrhosis

HepatocellularHepatocellularCarcinomaCarcinoma

HepaticHepaticDecompensationDecompensation

55-86%55-86%

Alcohol, Alcohol, HIV, and HIV, and

hepatitis B hepatitis B may may

accelerate accelerate fibrosisfibrosis

SpontaneousSpontaneousResolutionResolution

14-45%14-45%

2 – 4% per yr2 – 4% per yr 2 – 5% per yr2 – 5% per yr

20% in 20 yrs20% in 20 yrs

Seeff LB. Seeff LB. Hepatology Hepatology 2002;36 (Suppl 1):S35-46.2002;36 (Suppl 1):S35-46.

Staging HCV Liver FibrosisStaging HCV Liver Fibrosis

• Important part of chronic HCV work-upImportant part of chronic HCV work-up

• Identify cirrhosis:Identify cirrhosis: hepatocellular ca risk: need to screenhepatocellular ca risk: need to screen– Monitor for hepatic decompensationMonitor for hepatic decompensation– Strongly consider antiviral therapyStrongly consider antiviral therapy– Consider liver transplant evaluationConsider liver transplant evaluation

• Determine cirrhosis by:Determine cirrhosis by:– Liver biopsyLiver biopsy– Non-invasive testsNon-invasive tests

HCV Treatment in 2011HCV Treatment in 2011

GenotypeGenotype Therapeutic OptionsTherapeutic Options DurationDuration

11 PEG-IFN-2b + ribavirin + boceprevirPEG-IFN-2b + ribavirin + boceprevir

PEG-IFN-2a + ribavirin + telaprevirPEG-IFN-2a + ribavirin + telaprevir

24-48 wks24-48 wks**

24-48 wks24-48 wks**

2, 32, 3 PEG-IFN-2a or -2b + ribavirin PEG-IFN-2a or -2b + ribavirin 24 wks24 wks

44 PEG-IFN-2a or -2b + ribavirinPEG-IFN-2a or -2b + ribavirin

PEG-IFN + ribavirin + nitazoxanidePEG-IFN + ribavirin + nitazoxanide^̂

48 wks48 wks

48 wks48 wks

** Duration may depend upon treatment response Duration may depend upon treatment response^̂ Off-label usage Off-label usage

Time Points for Assessment of Time Points for Assessment of HCV Virologic ResponseHCV Virologic Response

• Week 4Week 4: rapid (RVR) = undetectable HCV: rapid (RVR) = undetectable HCV

• Week 12Week 12::

– Early virologic response (EVR) = 2 log IU/mL Early virologic response (EVR) = 2 log IU/mL HCV HCV

– Extended RVR (eRVR) = undetectable at wk 4 and 12Extended RVR (eRVR) = undetectable at wk 4 and 12

• Week 24Week 24: undetectable HCV: undetectable HCV

• Week 48Week 48: end-of-treatment (undetectable): end-of-treatment (undetectable)

• Week 72Week 72: sustained (SVR) = cure: sustained (SVR) = cure

Telaprevir Telaprevir Response-Guided TherapyResponse-Guided Therapy

HCV RNA Result*

Recommendation^

Treatment Wk 4

Treatment Wk 12

Previously

Untreated

or Relapse

Undetectable Undetectable

Wk 12 Wk 24

Total 24 wks

Detectable(≤1000 IU/mL)

Detectable(≤1000 IU/mL)

Wk 12 Wk 48

Total 48 wks

Prior Null or Partial Response

– –

Wk 12 Wk 48

Total 48 wks

PEG+RBV

* * If HCV RNA >1000 IU/mL at Wk 4 or 12, stop therapy. If HCV RNA >1000 IU/mL at Wk 4 or 12, stop therapy. ^̂ If treatment-naïve and cirrhosis: Consider PEG/RBV x 36 wks, even if undetectable at Wk 4 and 12. If treatment-naïve and cirrhosis: Consider PEG/RBV x 36 wks, even if undetectable at Wk 4 and 12.

Telaprevir + PEG + RBV

PEG+RBV

Telaprevir + PEG + RBV

PEG+RBVTelaprevir + PEG + RBV

SVR Rates with Telaprevir SVR Rates with Telaprevir for HCV Genotype 1for HCV Genotype 1

Trial Arms* SVR

ADVANCE(Naïve)

TVR/PRx12 wk PR x 12 wk 89%

TVR/PRx12 wk PR x 36 wk 75%

PR x 48 wk 44%

PROVE-2(Prior Rx)

TVR/PRx12 wk PR x 12 wk 51%

TVR/PRx24 wk PR x 24 wk 53%

PR x 48 wk 14%* * Note: PEG-IFN alfa-2a used in all arms.Note: PEG-IFN alfa-2a used in all arms. TPV = telaprevir; PR = PEG-IFN + ribavirinTPV = telaprevir; PR = PEG-IFN + ribavirin Jacobson IM et al. Jacobson IM et al. N Engl J Med 2011N Engl J Med 2011;364:2405-16.;364:2405-16.

Zeuzem S et al. et al. Zeuzem S et al. et al. N Engl J Med 2011N Engl J Med 2011;364:2417-28.;364:2417-28.

SVR Rates with Boceprevir SVR Rates with Boceprevir for HCV Genotype 1for HCV Genotype 1

Trial Arms* SVR

SPRINT-2(Naïve)

PRx4 wk BOC/PRx24 wk PRx20 wk 63%

PRx4 wk BOC/PRx44 wk 66%

PR x 48 wk 38%

RESPOND-2(Prior Rx)

PRx4 wk BOC/PRx32 wk PRx12 wk 59%

PRx4 wk BOC/PRx44 wk 66%

PR x 48 wk 21%* * Note: PEG-IFN alfa-2b used in all arms.Note: PEG-IFN alfa-2b used in all arms. BOC = boceprevir; PR = PEG-IFN + ribavirinBOC = boceprevir; PR = PEG-IFN + ribavirin Poordad F et al. Poordad F et al. N Engl J Med 2011N Engl J Med 2011;364:1195-206.;364:1195-206.

Bacon BR et al. Bacon BR et al. N Engl J Med 2011N Engl J Med 2011;364:1207-17.;364:1207-17.

Predictors of SVRPredictors of SVR

Virus Factors

• Low HCV RNA level• HCV genotype 2, 3

• Absence of HIV

Host Factors

•Younger age• Female sex• Non-Black

• No hepatic steatosis• No insulin resistance

• Less fibrosis• Adherence

Genetics

• Interleukin-28b

SVRSVR

Interleukin-28b Polymorphism:Interleukin-28b Polymorphism:Strongest Predictor of SVRStrongest Predictor of SVR

• Genetic polymorphismGenetic polymorphism– Interleukin-28b geneInterleukin-28b gene

– Chromosome 19Chromosome 19

• Homozygous for C allele:Homozygous for C allele:– Predicts HCV clearance Predicts HCV clearance

after acute infectionafter acute infection

– Genotype 1: predicts SVRGenotype 1: predicts SVR

• 82% SVR, CC genotype82% SVR, CC genotype

– Genotype 2, 3: less clearGenotype 2, 3: less clear

Ge D et al. Ge D et al. NatureNature 2009;461:399-401. 2009;461:399-401.Thompson AJ et al. Thompson AJ et al. GastroenterologyGastroenterology 2010;139:120-9. 2010;139:120-9.

Toxicities of HCV TherapyToxicities of HCV Therapy

• Tend to dominate treatment of HCVTend to dominate treatment of HCV

• Adverse events affect:Adverse events affect:– Quality of lifeQuality of life

– Adherence to antiviral therapy, follow-upAdherence to antiviral therapy, follow-up

• Discontinuation rates in trials: 14% – 22%Discontinuation rates in trials: 14% – 22%– Higher in clinical practiceHigher in clinical practice

Key Toxicities of PEG-IFN + RBVKey Toxicities of PEG-IFN + RBV

Adverse Effect % ReportedFatigue 54%

Influenza-like symptoms 43%

Weight loss 39%

Depression 22%

Dermatitis 21%

Thyroid dysfunction 6%

Pegylated InterferonPegylated Interferon

Adverse Effect % ReportedHemolytic anemia 22%

RibavirinRibavirin

Fried MW. Fried MW. Hepatology Hepatology 2002;36 (Supple 1):S237-44.2002;36 (Supple 1):S237-44.

Anemia During HCV TherapyAnemia During HCV Therapy

• Due to:Due to:– Suppression of erythropoiesis (IFN)Suppression of erythropoiesis (IFN)

– Hemolytic anemia (ribavirin)Hemolytic anemia (ribavirin)

• Incidence of Hgb <10 gm/dL: 15% - 35%Incidence of Hgb <10 gm/dL: 15% - 35%

of ribavirin dose: of ribavirin dose: likelihood of SVR likelihood of SVR

• Use of erythropoietin:Use of erythropoietin:– Halt, reverse anemia during HCV therapyHalt, reverse anemia during HCV therapy

– Allows maintenance of ribavirin dosageAllows maintenance of ribavirin dosage

– Consider if Hgb <10 gm/dLConsider if Hgb <10 gm/dL

Mira JA et al. Mira JA et al. Antivir TherAntivir Ther 2007;12:1225-35. 2007;12:1225-35.

Important Toxicities of Important Toxicities of Boceprevir + PEG-IFN + RibavirinBoceprevir + PEG-IFN + Ribavirin

Adverse Effect % ReportedFatigue 57%

Anemia 49%

Dysgeusia 43%

Nausea 43%

Insomnia 33%

Anorexia 25%

Irritability 22%

Rash 17%

Dry mouth 11%

Poordad F et al. Poordad F et al. N Engl J Med 2011N Engl J Med 2011;364:1195-206.;364:1195-206.

Important Toxicities of Important Toxicities of Telaprevir + PEG-IFN + RibavirinTelaprevir + PEG-IFN + Ribavirin

Adverse Effect % ReportedRash 56% (severe, 3%)

Fatigue 56%

Pruritus 47%

Nausea 39%

Anemia 36%

Diarrhea 26%

Anorectal discomfort 11%

Dysgeusia 10%

Anal pruritus 6%

Jacobson IM et al. Jacobson IM et al. N Engl J Med 2011N Engl J Med 2011;364:2405-16.;364:2405-16.

Management of ToxicitiesManagement of Toxicities

• Close follow-up: call with concerning eventClose follow-up: call with concerning event

• Rash: evaluate; antihistamine, topical steroidRash: evaluate; antihistamine, topical steroid

• Flu-like symptoms: ibuprofen, hydrationFlu-like symptoms: ibuprofen, hydration

• Depression: refer; antidepressantDepression: refer; antidepressant

• Weight loss: appetite stimulantWeight loss: appetite stimulant

• Anal discomfort: topical steroid, lidocaineAnal discomfort: topical steroid, lidocaine

• Anemia: ribavirin dose reduction and Anemia: ribavirin dose reduction and erythropoietinerythropoietin

Boceprevir vs. Telaprevir:Boceprevir vs. Telaprevir:ConsiderationsConsiderations

BoceprevirBoceprevir TelaprevirTelaprevir

1. Lead-in: potential to 1. Lead-in: potential to avoid protease inhibitoravoid protease inhibitor

1. Potential for shorter 1. Potential for shorter treatment durationtreatment duration

2. More complex regimen, 2. More complex regimen, 4 capsules q 8hrs4 capsules q 8hrs

2. Simpler regimen, 2. Simpler regimen, 3 capsules q 8hrs3 capsules q 8hrs

3. Anemia, dysgeusia 3. Anemia, dysgeusia 3. Rash, anal discomfort3. Rash, anal discomfort

4. Drug interactions4. Drug interactions 4. Drug interactions 4. Drug interactions

5. Consider in treatment-5. Consider in treatment- naïve, CC genotypenaïve, CC genotype

5. Consider in patients 5. Consider in patients previously treatedpreviously treated

Impact of Chronic HCV in HIVImpact of Chronic HCV in HIV

• Chronic HCV is common in HIV pts:Chronic HCV is common in HIV pts:– Due to shared routes of transmissionDue to shared routes of transmission

– 1/3 of HIV patients coinfected with chronic HCV1/3 of HIV patients coinfected with chronic HCV

• Antiretroviral therapy (ART) has Antiretroviral therapy (ART) has HIV- HIV-related complicationsrelated complications– Prolonged survival of HIV patientsProlonged survival of HIV patients

mortality related to HCV in HIVmortality related to HCV in HIV

Lo Re V et al. Lo Re V et al. Clin Liver Dis Clin Liver Dis 2008; 12:587-609.2008; 12:587-609.

Impact of HIV on HCV InfectionImpact of HIV on HCV Infection

clearance of HCVclearance of HCV

HCV RNA levelsHCV RNA levels

fibrosis progressionfibrosis progression

risk of cirrhosis risk of cirrhosis

risk of end-stage liver risk of end-stage liver disease (ESLD)disease (ESLD)

risk of hepatocellular risk of hepatocellular carcinoma (HCC)carcinoma (HCC) Natural History of HCVNatural History of HCV

ChronicChronic

ESLDESLDHCCHCC

HCV ExposureHCV Exposure

CirrhosisCirrhosis

Benhamou Y et al. Benhamou Y et al. Hepatology Hepatology 1999;30:1054-1058.1999;30:1054-1058.Graham CS et al. Graham CS et al. Clin Infect Dis Clin Infect Dis 2001;33:562-569.2001;33:562-569.

RecoveryRecovery

HIVHIV

Which HIV Patients Should be Which HIV Patients Should be Treated With PEG-IFN/RBV?Treated With PEG-IFN/RBV?

Disease ProgressionDisease Progression

Treatment ResponseTreatment Response

VirologicVirologic

HistologicHistologic

Adverse Effects of Adverse Effects of HCV TreatmentHCV Treatment

Competing MortalityCompeting Mortality

SVR Rates for PEG-IFN + RBV Arms SVR Rates for PEG-IFN + RBV Arms of HIV/HCV Treatment Trialsof HIV/HCV Treatment Trials

Chung RT et al. Chung RT et al. N Engl J MedN Engl J Med 2004;351:451-9. 2004;351:451-9.Torriani FJ et al. Torriani FJ et al. N Engl J MedN Engl J Med 2004;351:438-50. 2004;351:438-50.

Red = Genotype 1Red = Genotype 1Blue = Genotype 2, 3Blue = Genotype 2, 3

Rare SVR Without EVRRare SVR Without EVRin HIV/HCV-Coinfected Patientsin HIV/HCV-Coinfected Patients

No. Peg + RBV No EVR SVR

APRICOT1 289 85 2

ACTG 50712 106 63 0

RIBAVIC3 205 68 1

11Torriani FJ et al. Torriani FJ et al. N Engl J MedN Engl J Med 2004;351:438-50.2004;351:438-50.22Chung RT et al. Chung RT et al. N Engl J MedN Engl J Med 2004;351:451-9.2004;351:451-9.

33Carrat F et al. Carrat F et al. JAMAJAMA 2004;292:2839-48. 2004;292:2839-48.

Telaprevir + PEG-IFN/RibavirinTelaprevir + PEG-IFN/Ribavirinfor Genotype 1 HCV/HIV Patientsfor Genotype 1 HCV/HIV Patients

EligibilityEligibility• Chronic genotype 1 HCVChronic genotype 1 HCV• HCV treatment-naïveHCV treatment-naïve• Liver biopsyLiver biopsy• HIV infectionHIV infection

– No ARTNo ART• CD4 CD4 500/mm 500/mm33

• HIV HIV ≤ 100,000 c/mL≤ 100,000 c/mL

– Stable ARTStable ART• ATV/RTV or EFV + TDF/FTCATV/RTV or EFV + TDF/FTC• CD4 CD4 300/mm 300/mm33

• HIV HIV ≤ 50 c/mL≤ 50 c/mL

PEG-IFN / RBVPEG-IFN / RBV

TelaprevirTelaprevir750 mg q8h750 mg q8h**

++PEG-IFN / RBVPEG-IFN / RBV

0 wks 12 wks 48 wks0 wks 12 wks 48 wks

PEG-IFN / RBVPEG-IFN / RBVPlaceboPlacebo

++PEG-IFN / RBVPEG-IFN / RBV

Trial DesignTrial Design

Sulkowski MS et al. 18Sulkowski MS et al. 18thth CROI. Abstract 146LB. CROI. Abstract 146LB.

Arm 1Arm 1

Arm 2Arm 2

*Telaprevir dose 1125 mg q8 with EFV*Telaprevir dose 1125 mg q8 with EFV

Telaprevir + PEG-IFN/RibavirinTelaprevir + PEG-IFN/Ribavirinfor Genotype 1 HCV/HIV Patientsfor Genotype 1 HCV/HIV Patients

59 subjects enrolled:59 subjects enrolled:• No ART, n=13No ART, n=13• On ART, n=46On ART, n=46

– EFV-based, n=22EFV-based, n=22– ATV/RTV-based, n=24ATV/RTV-based, n=24

Main telaprevir AEs:Main telaprevir AEs:• Pruritus: 35%Pruritus: 35%• Nausea: 35%Nausea: 35%• Anorexia: 19%Anorexia: 19%

Undetectable HCV RNA at Week 12Undetectable HCV RNA at Week 12

No ART EFV-Based ATV-Based ART ART

Blue = Telaprevir + PEG-IFN + ribavirinBlue = Telaprevir + PEG-IFN + ribavirinRed = PEG-IFN + ribavirinRed = PEG-IFN + ribavirin

Sulkowski MS et al. 18Sulkowski MS et al. 18thth CROI. Abstract 146LB. CROI. Abstract 146LB.

Telaprevir + Peg-IFN and RBV: Sustained Virologic Response (SVR12)

Dieterich D, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 46.

Dug-Drug Interactions:Dug-Drug Interactions:Telaprevir, Boceprevir, and ARVsTelaprevir, Boceprevir, and ARVs

• Phase 1 studies in healthy volunteersPhase 1 studies in healthy volunteers

• Telaprevir drug levels:Telaprevir drug levels: 50% w/ LPV/RTV50% w/ LPV/RTV 30% w/ DRV/RTV, FOS/RTV30% w/ DRV/RTV, FOS/RTV with EFV (requires with EFV (requires dosage, 1250 mg TID) dosage, 1250 mg TID)

• Boceprevir drug levels:Boceprevir drug levels: 40% with EFV40% with EFV– No change with PEG-IFN 2b, TDF, RTVNo change with PEG-IFN 2b, TDF, RTV

Kasserra C et al. 18th CROI. Abstract 118.Kasserra C et al. 18th CROI. Abstract 118.Van Heeswijk R et al. 18Van Heeswijk R et al. 18thth CROI. Abstract 119. CROI. Abstract 119.

Boceprevir + Peg-IFN and RBV: Sustained Virologic Response (SVR12)

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Sulkowski M, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 47.

Notable Adverse Events Seen inHCV PI Trials

Telaprevir1

TVR+P/R (N=38)

P/R (N=22)

Pruritus 39% 9%

Headache 37% 27%

Nausea 3% 23%

Rash 34% 23%

Pyrexia 21% 9%

Depression 21% 9%

Neutropenia 24% 23%

Anemia 18% 18%

Insomnia 13% 23%

Decreased Appetite 11% 18%

Weight Decreased 13% 23%

Boceprevir2

BOC+P/R(N=64)

P/R (N=34)

Anemia 41% 26%

Pyrexia 36% 21%

Asthenia 34% 24%

Decreased appetite 34% 18%

Diarrhea 28% 18%

Dysgeusia 28% 15%

Vomiting 28% 15%

Flu-like illness 25% 38%

Neutropenia 19% 6%

Erythropoietin use 38% 21%

1. Dieterich D, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 46; 2. Sulkowski M, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 47.

Significant Drug-drug interactions between Boceprevir

and HIV PIs

No significant drug-drug interactions between boceprevir and raltegravir2

PK Parameter GMPI/r or BOC

GMPI/r + BOC

GMR 90% CI

ATV/r + BOC

ATV AUC (ng●hr/mL) 39,900 26,000 0.65 (0.55, 0.78)

ATV Cmin (ng/mL) 693 357 0.51 (0.44, 0.61)

BOC AUC (ng●hr/mL) 4,840 4,610 0.95 (0.87, 1.05)

BOC Cmin (ng/mL) 106 86.6 0.82 (0.68, 0.98)

DRV/r + BOC

DRV AUC (ng●hr/mL) 60,300 33,500 0.56 (0.51, 0.61)

DRV Cmin (ng/mL) 3,220 1,320 0.41 (0.38, 0.45)

BOC AUC (ng●hr/mL) 5,350 3,650 0.68 (0.65, 0.72)

BOC Cmin (ng/mL) 94.7 61.5 0.65 (0.56, 0.76)

LPV/r + BOC

LPV AUC (ng●hr/mL) 117,000 77,000 0.66 (0.60, 0.72)

LPV Cmin (ng/mL) 6,730 3,800 0.57 (0.49, 0.65)

BOC AUC (ng●hr/mL) 6,040 3,310 0.55 (0.49, 0.61)

BOC Cmin (ng/mL) 91.9 39.8 0.43 (0.36, 0.53)

Hulskotte E, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 771LB; de Kanter C, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 772LB.

Options for Treating HIV/HCV Co-Infected Patients

• Dose modification of ARV agents– Limited Data (with efavirenz)– PK interaction may not entirely explain lack of effect– May not be practical (telaprevir “package”)

• Modify ARV regimen (raltegravir-no interaction)– Introduce new toxicity – Risk loss of HIV control

• Treat HCV without HIV therapy– Risk of HIV disease progression– Decrease chance of HCV response

HCV Re-infection Among MSM in Germany

•Retrospective analysis of cases of HCV re-infection in 4 German HIV and hepatitis centers•Re-infection defined as:

•Genotype switch•Detectable VL ≥6 month

after SVR following HCV therapy

•Detectable VL ≥6 month after spontaneous clearance

•45 cases among MSM, all thought to be sexually acquired

Patterns of Re-Infection

45 HIV + MSM with acute HCV infection

40 SVR40 SVR5 SC

3 SC 4 SC2 SVR

2 SVR 16 SVR16 SVR 12 CHC12 CHC

1 SC

1 SVR

1 SVR 2 SVR2 SVR 2 CHC2 CHC

1 SC

SC= spontaneous clearance, SVR=sustained virological response, CHC=Chronic HCV

Episode 4

Episode 3(1 pending)

Episode 2(8 pending)

Episode 1

Ingiliz P, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 752.