HIV/HCV Co-Infection

Objectives

• Introduction
• Why PLHIV are a priority population for HCV management
• HIV/HCV Clinical Trials
• HIV/HCV Interactions
• Dose Adjustments
 HIV/HCV Co-infection
 Shared rout of infection
• Exposure to infected blood (IDU, non-sterile tattoos, needle sticks, remote
recipient of blood products)
• Sexual Intercourse[ MSM(>>>HIV), comorbid STI, Trauma]
• Perinatal/Vertical transmission
 Poor HIV control/absence of ART associated with worse outcome
• Though effective ART doesn’t fully mitigate increased risk seen with coinfection
 HIV/HCV confected patients experience increased rate of advanced liver
diseases , liver related and all cause mortality, relative to HCV mono-
infected patient
 HCV screening & treatment is a priority in PLHIV
HIV/HCV coinfection……..
• Comparable efficacy of DAA regimens in HIV/HCV Coinfection, relative
to HCV mono infection
• Shorter course not advisable, no data for rare Genotypes(5,6)
• Increased potential to DDI with ART & DAAs
• ART for HIV shouldn’t be interrupted to pursue HCV treatment
•  change in ART may be
• Reasonable to defer HCV therapy until ART for HIV tolerability confirmed
• Increased risk of DDI & drug adverse effect in other OI (e.g- TB)
HIV affects the transmission and natural history of
HCV
• HIV negatively impacts HCV disease progression
PLHIV have higher rates of chronicity, higher viral loads and accelerated disease progression and mortality

Meta-analysis: Adjusted RR of advanced cirrhosis or

decompensated liver disease in co-infected patients
compared to HCV-mono-infected (J Hepatol 2008; 48:
353–67)

Relative risk of death in HIV/HCV co-infected ESLD patients is 2.26 greater than in HCV-monoinfected ESLD patients
Hepatology. 2005 Apr;41(4):779-89
• HCV is more efficiently transmitted in HIV-infected mothers
• MTCT rate is tripled for HIV positive mothers 17 – 25%, compared to HIV negative (5 – 8%)

J Infect Dis. 1998;177(6):1480–8, J Infect Dis. 2005;192(11):1880–9)

 HIV/HCV co-infection burden
• Global estimate of 6.2% (3.4 – 11.9%) HCV
prevalence in PLHIV
• Estimated 15-30(≈21)% of PLHIV in US have
evidence for prior HCV exposure/infection
• Co-infection prevalence varies across risk
groups(IDU> MSM> Hetroseual contacts)
• PLHIV & IDU  HCV coninfection ≈ 62-80%
• Spontaneous clearance of HCV is lower in
PLHIV
• Coinfection is associated accelerated rates of
liver fibrosis & cirrhosis
• Pre-DAA era, progression fibrosis 2x monoinfected
HCV on HIV: ↑risk of hepatotoxicity with ART
• Progression to cirrhosis est 12-16yrs earlier
in Coinfection relative to HCV moinfection
• 25% of coinfected patient develop cirrhosis
after 10-15yrs( vs 2-6% in monoinfection
• Incidence of hepatic decompasation > in
coinfected vs moninfected ( 7.4 % vs 4.8%
@ 10yrs)
• Pts with coinfection develop HCC at younger
age and have more aggressive tumors
relative to HCV monoinfected individuals
HCV prevalence in specific populations living with
HIV
2.4% in general population
(data from 2002
4% in – 2015)
pregnant women & those exposed
through heterosexual contact

6.4% in men who have sex with men (MSM) 82.4% in people who inject drugs

Platt L et al. Lancet Infect Dis (2016) http://dx.doi.org/10.1016/S1473-3099(15)00485-5

Treatment of HCV and HIV Infection in Persons
With Coinfection
• All persons with HIV should be
treated with potent ART,
especially those with HIV/HCV
co-infection[1]
• HIV infection is independently
associated with HCV disease
progression[2]
1. DHHS Guidelines. 2018. 2. AASLD/IDSA HCV Guidelines. 2017.
• HCV treatment should also be a priority
for persons with HCV/HIV coinfection[2]
• Efficacy and adverse event rates of HCV
DAAs among those with
HCV/HIV coinfection are similar to
those observed with HCV alone
• Co-treatment “requires continued
awareness and attention to the
complex drug–drug interactions that
can occur between DAAs and
antiretroviral medications”
 Disease Progression in HCV Mono-infection vs HCV/HIV Co-
infection With or Without HIV Suppression
Retrospective cohort study of HCV-infected, treatment-naive patients in the Veterans Health Administration (N = 10,359)

If CD4+ < 200/mm2: +203% excess risk

If HIV-1 RNA < 1000 copies/mL: +65% excess risk If CD4+ ≥ 200/mm2: +56% to 63% excess risk
If HIV-1 RNA ≥ 1000 copies/mL: +82% excess risk

Lo Re III V, et al. Ann Intern Med. 2014;160:369-379

 All PLHIV should be screened for HCV & all co-
infected patients should be prioritized for treatment

www.hcvguidelines.org
HIV/HCV Co-infected patients should be treated
using the same regimens as HCV mono-infected
patients

www.hcvguidelines.org.
 HCV DAAs Have Similar Efficacy in
Persons With and Without HIV Co-infection
Efficacy Across Separate Phase III Studies of GT1-6 HCV Infection With GLE/PIB, GZR/EBR, SOF/LDV, or SOF/VEL

*Most data reported for these studies are from treatment-naive patients with GT1/4 HCV infection receiving
12-wk regimens

1. Forns X, et al. Lancet Infect Dis. 2017;10:1062-1068. 2. Zeuzem S, et al. Ann Intern Med. 2015;163:1-13. 3. Afdhal N, et al. N Engl J Med.
2014;370:1889-1898. 4. Feld JJ, et al. N Engl J Med. 2015;373:2599-2607. 5. Rockstroh J, et al. IAS 2017. Abstract MOAB0303. 6. Rockstroh JK,
et al. Lancet HIV. 2015;2:e319-e327. 7. Naggie S, et al. N Engl J Med. 2015;373:705-713. 8. Wyles D, et al. Clin Infect Dis. 2017;65:6-12
 Efficacy……….
Regimen Phase Size Design SVR
FDA Approved
Daclatasvir + sofosbuvir III 168 RCT: 8 vs 12 (N=127) weeks 97%
Ledipasvir/sofosbuvir II 50 Single arm: 12 weeks 98%
Paritaprevir/r/ombitasvir + II 63 RCT: 12 vs 24 weeks 92%
dasabuvir + ribavirin
Simeprevir + sofosbuvir N/A 19/31 Observational 95/77%
Sofosbuvir + ribavirin III 497 Single arm: 12 or 24 weeks 81-91%
Grazoprevir + elbasvir III 218 Single arm: 12 weeks 95%

Osinusi et al, JAMA 2015; Naggie et al, NEJM 2015; Sulkowski et al, JAMA 2015;
Wyles et al, NEJM 2015; Rockstroh et al, Lancet HIV 2015 Abstract; Grant et al, CROI 2015 Abstract 649;
Gilmore et al, CROI 2015 Abstract 645
 AASLD/IDSA Recommendations for First-line HCV
Treatment in HCV/HIV Coinfection

*If GT1a with BL NS5A RASs for EBR, 12 wks not recommended; can increase duration to 16 wks with RBV (alternative). †Some data to support
8 wks in GT1, but 8 wks not recommended in HIV/HCV coinfection. ‡If decompensated cirrhosis, do not use HCV protease inhibitors. §If BL
Y93H RAS present in GT3, add RBV or consider SOF/VEL/VOX. ‖If also cirrhotic, increase duration to 12 wks .

AASLD/IDSA HCV Guidelines. 2017 Slide credit: clinicaloptions.com

Common Scenarios for the Co-treatment of
HCV and HIV Infection
1. Persons taking ART with HIV 2. Persons not taking ART who
RNA suppression who plan to plan to initiate HCV DAA therapy
initiate HCV DAA therapy • Decision:
• Decisions: • Which infection to treat first, or
• Selection of HCV DAA regimen whether to start both treatments
• Adjustment of ART to facilitate a simultaneously
specific DAA regimen
 HIV/HCV Drug–Drug Interactions

*Monitor for tenofovir toxicity if used with TDF. †No clinically significant drug interaction per prescribing information.
‡Guidelines recommend monitoring liver enzymes owing to lack of clinical safety data. §No information in prescribing
information.
DHHS Guidelines. 2018
 HIV/HCV Drug–Drug Interactions……..
Sofosbuvir Ledipasvir Daclatasvir Standard dose of DCV is
Inhibitor of
Substrate of
Inhibitor/
OATP1B1/3, BCRP,
60mg daily
DDI Substrate of P-gp
P-gp and BCRP
and BCRP
Substrate of P-gp *Decrease DCV dose to
and CYP3A4
ATV/r No data LDV ↑; ATV ↑ DCV ↑*
30mg daily
LPV/r No data No data ALLY-2 ↔ **Increase DCV dose to
TPV/r No data No data No data 90mg daily
EFV SOF ↔; EFV ↔ ION-4 ↔ DCV ↓**
NVP SOF ↔; EFV ↔ ION-4 ↔ No data** Combination of LDV and TDF
ETV No data No data No data** is safe with all antiretrovirals
RAL SOF ↔; RAL ↔ LDV ↔; RAL ↔ ALLY-2 ↔ except boosted protease
DLG No data LDV ↔; DOL ↔ ALLY-2 ↔
inhibitors (ex. ATV/r).
TDF SOF ↔; TFV ↔ LDV ↔; ↑TFV DCV ↔; TFV ↔
ABC No data No data ALLY-2 ↔ Renal monitoring is
3TC/FTC ↔ ↔ ALLY-2 ↔ recommended for all LDV +
TDF dosing
Slide courtesy of Jennifer Kiser
DDI b/n DAAs and ART………………..

Hcvguidelines.org
 DAA/ARV Interaction Score Card: Ethiopia
Specific
Standard dose of DCV is
Sofosbuvir Ledipasvir Daclatasvir
60mg daily
Inhibitor of *Decrease DCV dose to
Inhibitor/
DDI Substrate of Substrate of P-gp OATP1B1/3, BCRP, 30mg daily
P-gp and BCRP and BCRP Substrate of P-gp
and CYP3A4 **Increase DCV dose to
90mg daily
ATV/r No data LDV ↑; ATV ↑ DCV ↑*
LPV/r No data No data ALLY-2 ↔
Combination of LDV and TDF
EFV SOF ↔; EFV ↔ ION-4 ↔ DCV ↓** is safe with all antiretrovirals
NVP SOF ↔; EFV ↔ ION-4 ↔ No data** except boosted protease
TDF SOF ↔; TFV ↔ LDV ↔; ↑TFV DCV ↔; TFV ↔ inhibitors (ex. ATV/r).
ABC No data No data ALLY-2 ↔ Renal monitoring is
3TC/FTC ↔ ↔ ALLY-2 ↔ recommended for all LDV +
TDF dosing
Slide courtesy of Jennifer Kiser
 Co-treatment of HIV and HCV co-infection
• For many patients, initiation of ART should be prioritized; however,
HIV treatment and HIV-1 RNA suppression are not required before
HCV DAAs
• Treatment readiness for 8-12 wks of HCV DAAs may be different than for
lifelong ART
• HCV treatment and cure may serve to facilitate HIV care engagement
• SVR may reduce the risk of drug-induced liver injury
• If ART is initiated first, consider delaying HCV DAAs for 4-6 wks to
confirm tolerability and HIV-1 RNA response

AASLD/IDSA HCV Guidelines. 2017

Common DDIs With Non-ART, Non-DAA Co-
medications
• PPIs
• Statins
• Anti-seizure drugs
• Carbamazepine
• Phenytoin
• Herbals
• Over-the-counter medications (including antacids)
 HCV Care Continues Past Achievement of SVR

Falade-Nwulia O, et al. J Hepatol. 2017;66:267-269. AASLD/IDSA HCV Guidelines. 2017.

 Key Takeaways
• HIV and HCV affect similar at-risk populations and share transmission
routes
o All PLHIV should be screened for HCV
• HCV/HIV co-infected patients higher rates of chronicity, higher viral
loads and accelerated disease progression and mortality compared to
HCV mono-infected
• HCV/HIV co-infected:
o Should be prioritized for treatment
o Should be treated with the same regimens as HCV mono-infected
o May need to adjust drug dosage depending on ART regiment
o Achieve similar SVR rates as HCV mono-infected