What are DHHS guidelines for antiretroviral therapy of HIV infection with HCV coinfection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

Approximately 25% of persons with HIV infection are coinfected with HCV. [129]  HCV infection in the presence of HIV infection progresses to cirrhosis or end-stage liver disease twice as quickly as in HCV monoinfection. [130]  Although HIV disease progression has not been directly linked to HCV coinfection, it is significantly influenced by the lower rise in CD4 counts once antiretroviral therapy is initiated and the increased risk for hepatotoxicity with antiretroviral therapy. Historically, treatment outcomes, as measured by sustained virologic response 12 weeks after treatment completion (SVR12), were significantly lower in patients with HCV and HIV coinfection. [131, 132] However, with the approval and use of direct-acting antivirals, providers can expect similar SVR12 rates as those with HCV mono-infection. [133]

Because of its faster disease progression, HIV treatment is a greater priority than treatment for HCV; therefore, HIV suppression and antiretroviral regimen stability is achieved first. However, select patients may be unable to tolerate antiretrovirals and experience hepatic toxicity. In these cases, HCV is treated and then antiretrovirals can be initiated successfully.

Depending on the HCV genotype, presence of cirrhosis, and previous antiviral treatment, several highly effective regimens are available to treat HCV. Combination therapy is always used to target at least 2 of the 3 current drug targets: the NS5A, NS5B, and NS3/4A sites. In certain situations, ribavirin is still used; however, pegylated interferon has been phased out as a treatment option.

Drug interactions are now the greatest obstacle in treating HIV/HCV co-infected patients. In terms of safety outcomes, tenofovir DF used with ledipasvir or velpatasvir can lead to an increase in serum creatinine, particularly when combined with a pharmacokinetic booster. [134] The use of tenofovir DF should be avoided in these situations when the patient’s baseline estimated CrCL is under 60 mL/min; increased monitoring is sufficient when used in those with a CrCL > 60 mL/min. [133] Alternatively, tenofovir AF can be used without concern and can provide an easy switch option in these patients. The combination of protease inhibitors used to treat HIV (e.g., boosted darunavir and atazanavir) and NS3/4A protease inhibitors used to treat HCV (e.g. grazoprevir, pibrentasvir) can lead to increased risk of hepatic toxicity and should be avoided. Although ribavirin is generally avoided when possible due to increased toxicities and pill burden, situations arise which necessitate its use. Coadministration of zidovudine should be avoided due to increased hematologic toxicity risk. [133]

From an efficacy standpoint, the inductive effects of efavirenz and etravirine significantly reduce concentrations of elbasvir/grazoprevir, glecaprevir/pibrentasvir, and velpatasvir/sofosbuvir; therefore, these combinations should be avoided. [133] Numerous non-antiretroviral interactions are possible and must be considered when creating an HCV treatment plan as well.

In some situations, a patient may be unable to switch an antiretroviral regimen that has significant potential interactions with the recommended HCV treatment regimens. In such cases, daclatasvir combined with sofosbuvir is the preferred treatment. [133] Ribavirin may be added on, depending on the HCV genotype and presence of cirrhosis. Daclatasvir is a CYP3A4 substrate and will require dose adjustments when used with moderate 3A4 inducers (e.g., efavirenz, etravirine) and strong 3A4 inhibitors (e.g., atazanavir boosted with either ritonavir or cobicistat or elvitegravir boosted with cobicistat). Boosted darunavir and unboosted atazanavir are safe to use with standard dose daclatasvir. [135]

The duration of HCV treatment has decreased substantially with the updated direct-acting antivirals and ranges from 8 weeks to 12 weeks for the preferred regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, and velpatasvir/sofosbuvir) depending on the presence of cirrhosis. Mono-infected, non-black patients with a baseline HCVRNA under 6 million IU/mL qualify for an 8 week treatment duration; however, this regimen has not been studied in coinfected patients and, therefore, the treatment duration should remain 12 weeks. [133]

A final and significant consideration in HCV treatment is the potential for reactivation of HBV infection. A boxed warning was issued by the FDA in 2016 after reports of patients experiencing HBV reactivation leading to a liver transplant in one patient and death in two others. [136] No specific genotype, direct-acting antiviral, or patient characteristic has been identified as a risk factor for this complication. All patients should be tested for HBV prior to HCV treatment initiation and vaccinated when needed. Patients infected with HBV and HIV should already be on treatment for both infections; this should be continued throughout the duration of HCV treatment. [133]


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