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Hepatitis C Virus (HCV)/HIV Co-infection

(Last updated:17/10/2017; last reviewed:17/10/2017)

Panel recommendations

  • All people with HIV should be screened for hepatitis C virus (HCV) infection. Patients at high risk of HCV infection should be screened annually and whenever HCV infection is suspected (AIII).
  • Antiretroviral therapy (ART) may slow the progression of liver disease by preserving or restoring immune function and reducing HIVrelated immune activation and inflammation. For most HCV/HIV-coinfected patients, including those with cirrhosis, the benefits of ART outweigh concerns regarding drug-induced liver injury. Therefore, ART should be initiated in all HCV/HIV-coinfected patients, regardless of CD4 T lymphocyte (CD4) cell count (AI).
  • Initial ART regimens recommended for most HCV/HIV-coinfected patients are the same as those recommended for individuals without HCV infection. However, when treatment for both HIV and HCV is indicated, the regimen should be selected with special considerations of potential drug-drug interactions and overlapping toxicities with the HCV treatment regimen (see discussion in the text below and in Table 12)
  • In patients with lower CD4 counts (eg, <200 cells/mm3), ART should be initiated promptly (AI) and HCV therapy may be delayed until the patient is stable on HIV treatment (CIII).
  • All patients with HCV/HIV coinfection should be evaluated for HCV therapy and have their liver fibrosis stage assessed to inform the length of their therapy, ribavirin need (a concern with some regimens), and subsequent risk of hepatocellular carcinoma and liver disease complications.
  • Persons with chronic HCV/HIV coinfection should be screened for active and prior hepatitis B virus (HBV) infection by testing for the presence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B surface (HBsAb) and core (HBcAb total or IgG). Persons who are not immune to HBV infection (HBsAb-negative) should receive anti-HBV vaccination (AIII).
  • HBV reactivation has been observed in persons with HBV infection during interferon-free HCV treatment. Accordingly, persons with HCV/HIV coinfection and active HBV infection (HBsAg-positive) should receive ART that includes two agents with anti-HBV activity prior to initiating HCV therapy (AIII).

Rating of Recommendations:
  A = Strong; B = Moderate; C = Optional
Rating of Evidence:  I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = expert opinion

#1837 HIV/Hepatitis C Virus Coinfection
June 2018 - Feedback

In Australia, the PBS now lists the following all-oral regimens for treatment of chronic hepatitis C infection in Australia, regardless of liver disease stage or ongoing drug and alcohol use:

For genotype 1 – sofosbuvir plus ledipasvir OR sofosbuvir plus daclatasvir ± ribavirin OR grazoprevir plus elbasvir ± ribavirin
For genotype 2 – sofosbuvir plus ribavirin
For genotype 3 – sofosbuvir plus daclatasvir OR sofosbuvir plus ribavirin
For genotype 4 – sofosbuvir plus PEG-IFN (and) ribavirin OR grazoprevir plus elbasvir ± ribavirin
For genotype 5-6 – sofosbuvir plus PEG-IFN (and) ribavirin

Guidelines and resources for the management of Hepatitis C are available at http://www.ashm.org.au/HCV/ and a treatment guideline is available at http://www.hepcguidelines.org.au 

Treatment with these regimens from clinical trials is expected to produce sustained virological response (SVR) rates similar to mono-infected patients.

Clinically significant Drug-drug interactions relevant to HIV treatments should be considered and a drug interaction search can be undertaken at http://www.hep-druginteractions.org/. An interaction between efavirenz and daclatasvir means that daclatasvir requires higher dosing (90 mg vs standard 60 mg once daily), while another interaction between ritonavir-boosted atazanavir and daclatasvir means that daclatasvir is dosed at a lower level (30 mg vs 60 mg once daily). Paritaprevir-ritonavir/ombitasvir/dasabuvir has significant drug-drug interactions, many resulting from the inclusion of ritonavir in the regimen and is uncommonly chosen because of pill burden and drug interactions. Sofosbuvir/daclatasvir has the advantage of being pangenotypic (activity against genotypes 1-6, although only PBS listed for genotypes 1 and 3), whereas sofosbuvir/ledipasvir has poorer activity against genotypes 2-3.

#1810 - When to start
October 2017 - Feedback  


The ASHM Sub-Committee for Guidance on HIV Management in Australia has developed clinical guidance for the Australian context in regards to this topic.  Please see "When to start antiretroviral therapy in people with HIV".

The treatment of hepatitis C virus (HCV) infection is rapidly evolving. Patients HCV/HIV coinfection are treated with all-oral, direct-acting antiviral (DAA) HCV regimens can achieve sustained virologic response (HCV cure) rates comparable to those of patients with HCV monoinfection.1-3 This section of the Guidelines focuses on hepatic safety and drug-drug interaction issues related to HCV/HIV coinfection and the concomitant use of antiretroviral (ARV) agents and HCV drugs. For specific guidance on HCV treatment, please refer to http://www.hcvguidelines.org/.

Among patients with chronic HCV infection, approximately one-third progress to cirrhosis, at a median time of less than 20 years.4,5 The rate of progression increases with older age, alcoholism, male sex, and HIV infection.6-9 A meta-analysis found that HCV/HIV-coinfected patients had a three-fold greater risk of progression to cirrhosis or decompensated liver disease than HCV-monoinfected patients.8 The risk of progression is even greater in HCV/HIV-coinfected patients with low CD4 T lymphocyte (CD4) cell counts. Although antiretroviral therapy (ART) appears to slow the rate of HCV disease progression in HCV/HIV coinfected patients, several studies have demonstrated that the rate continues to exceed that observed in patients without HIV infection.10,11 Whether HCV infection accelerates HIV progression, as measured by AIDS-related opportunistic infections (OIs) or death,12 is unclear. Although some older ARV drugs that are no longer commonly used have been associated with higher rates of hepatotoxicity in patients with chronic HCV infection,13,14 newer ARV agents currently in use appear to be less hepatotoxic.

Assessment of HIV/HCV Virus Coinfection

  • All HIV-infected patients should be screened for HCV infection using sensitive immunoassays licensed for detection of antibody to HCV in blood15. At-risk HCV-seronegative patients should undergo repeat testing annually. HCV-seropositive patients should be tested for HCV RNA using a sensitive quantitative assay to confirm the presence of active infection. Patients who test HCV RNA-positive should undergo HCV genotyping and liver disease staging as recommended by the HCV guidelines (see http://www. hcvguidelines.org/).
  • Patients with HIV/HCV coinfection should be counseled to avoid consuming alcohol and to use appropriate precautions to prevent transmission of HIV and/or HCV to others.
  • People with chronic HCV/HIV coinfection should be screened for active and prior hepatitis B virus (HBV) infection by testing for the presence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B surface (HBsAb) and core (HBcAb total or IgG).
  • Persons with evidence of active HBV infection (HBsAg) should be further evaluated and treated with ART that includes agents with anti-HIV and HBV activities (AIII).
  • Those who are not immune to HBV infection (HBsAb-negative) should receive anti-HBV vaccination.
  • HIV/HCV-coinfected patients who are susceptible to hepatitis A virus (HAV) or hepatitis B virus (HBV) infection should be vaccinated against these viruses.
  • All patients with HIV/HCV coinfection should be evaluated for HCV therapy.

Antiretroviral Therapy in HIV/Hepatitis C Virus Coinfection

When to start antiretroviral therapy

Initiation of ART for persons with HCV/HIV coinfection should follow the recommendations for all persons with HIV infection, taking into account the needs for concurrent HCV treatment with oral DAA regimens and the individual’s HBV status.

Antiretroviral Drugs to Start and Avoid

Initial ARV combination regimens recommended for most HIV treatment-naive patients with HCV are the same as those recommended for patients without HCV infection. Special considerations for ARV selection in HCV/HIV-coinfected patients include the folllowing:

  • When both HIV and HCV treatments are indicated, the ARV regimen should be selected with careful consideration of potential drug-drug interactions (see Table 12) and overlapping toxicities with the HCV treatment regimen.
  • HBV reactivation has been observed in persons with HBV infection during interferon-free HCV treatment.16,17 Therefore, persons with HCV/HIV coinfection and active HBV infection (HBsAg-positive) should receive ART that includes agents with anti-HBV activity (such as tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF] plus emtricitabine or lamivudine) prior to initiating HCV therapy (AIII).
  • Cirrhotic patients should be carefully evaluated by an expert in advanced liver disease for signs of liver decompensation according to the Child-Turcotte-Pugh classification system. This assessment is necessary because hepatically metabolized ARV and HCV DAA drugs may be contraindicated or require dose modification in patients with Child-Pugh class B and C disease (see Appendix B, Table 7).

Hepatotoxicity:

Drug-induced liver injury (DILI) following the initiation of ART is more common in HCV/HIV-coinfected patients than in those with HIV monoinfection. HVC/HIV coinfected individuals with advanced liver disease (eg, cirrhosis, end-stage liver disease) are at greatest risk for DILI.29 Eradicating HCV infection with treatment may decrease the likelihood of ARV-associated DILI.30 Alanine Downloaded from https://aidsinfo.nih.gov/guidelines on 7/8/2018 Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV J-8 aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be monitored 4 to 8 weeks after initiation of ART and at least every 6 to 12 months thereafter, and if clinically indicated. Mild to moderate fluctuations in ALT and/or AST are typical in individuals with chronic HCV infection. In the absence of signs and/or symptoms of liver disease or increases in bilirubin, these fluctuations do not warrant interruption of ART. Patients with significant ALT and/or AST elevation should be carefully evaluated for signs and symptoms of liver insufficiency and for alternative causes of liver injury (e.g., acute hepatitis A virus [HAV] or HBV infection, hepatobiliary disease, or alcoholic hepatitis).

Concurrent Treatment of HIV and Hepatitis C Virus Infection

Guidance on the treatment and management of HCV in adults with and without HIV can be found at http:// www.hcvguidelines.org/. Several ARV drugs and HCV DAAs have the potential for clinically significant pharmacokinetic drug-drug interactions when used in combination. Prior to starting HCV therapy, the ART regimen may need to be modified to reduce the drug-drug interaction potential. Table 12 below provides recommendations on the concomitant use of selected drugs for treatment of HCV and HIV infection. In patients on modified ART who have suppressed plasma HIV RNA, HIV RNA should be measured within 4 to 8 weeks after changing HIV therapy to confirm the effectiveness of the new regimen. After HCV treatment is completed, the modified ART regimen should be continued for at least 2 weeks before reinitiating the original regimen. Continued use of the modified regimen is necessary because of the prolonged half-life of some HCV drugs and the potential risk of drug-drug interactions if a prior HIV regimen is resumed soon after HCV treatment is completed.

Table 12. Concomitant Use of Selected HIV Drugs and FDA-Approved HCV Drugs for Treatment ofHCV in HIV-Infected Adults

The recommendations in this table for concomitant use of selected HIV drugs with FDA-approved HCV direct-acting antiviral (DAA) drugs are based on available pharmacokinetics interaction data or predictions based on the known metabolic pathway of the agents. In some cases, there are not enough data to make any recommendations, and these instances are indicated in the table. In all cases where HIV and HCV drugs are used concomitantly, patients should be closely monitored for HIV and HCV virologic efficacy and potential toxicities. As the field of HCV therapy is rapidly evolving, readers should also refer to the latest drug product labels and HCV guidelines (www.hcvguidelines.org/) for updated information.

 
 References

 

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