HCV treatment in people with HIV–HCV coinfection

The treatment regimens for HCV in people with HIV are the same as those used for HCV mono-infection and, as noted, the response rates are equivalent.[91-96],[102] Selection of DAA therapy for people with HIV–HCV coinfection should be as for HCV mono-infection, with the important caveat that ART increases the likelihood of clinically significant drug–drug interactions. A careful assessment of potential drug–drug interactions between DAAs and ART and drugs prescribed to manage HIV-related complications and comorbidities should be made before commencing HCV treatment, using the University of Liverpool’s Hepatitis Drug Interactions website.

Caution is warranted even for combinations of HIV ART and HCV DAAs where a specific drug–drug interaction issue is not expected or reported, as further information on interactions is likely to emerge. Due to extensive drug–drug interactions, tipranavir should be avoided with concurrent HCV DAA therapy.

Drug interaction studies with velpatasvir plus sofosbuvir have been performed in HIV and HCV seronegative volunteers. Tenofovir exposures are increased when velpatasvir is coadministered with tenofovir disoproxil fumarate (TDF), which may be problematic for individuals with eGFR values of less than 60 mL/min or in those receiving ritonavir- or cobicistat-containing ART with tenofovir. The use of tenofovir alafenamide (TAF) in place of TDF should be considered in those requiring ritonavir- or cobicistat-containing ART — the combination of velpatasvir with TAF is not expected to cause kidney injury. If the combination of TDF with a ritonavir- or cobicistat-containing ART is required, renal parameters should be checked at baseline and regularly thereafter while taking sofosbuvir plus velpatasvir.

Velpatasvir exposures are significantly reduced with efavirenz, and this combination is not recommended. Etravirine has not been studied with sofosbuvir plus velpatasvir but is also not recommended. Indirect bilirubin level increases have been reported when sofosbuvir plus velpatasvir is used in patients taking atazanavir–ritonavir, but these changes are not considered clinically significant.

Coadministration of glecaprevir plus pibrentasvir and OATP1B inhibitors, including all HIV protease inhibitors, is contraindicated because of markedly increased exposure to both glecaprevir and pibrentasvir and an increased risk of elevation in ALT level.

Coadministration with cobicistat-boosted HIV protease inhibitors has not been studied but is not recommended. Coadministration with elvitegravir–cobicistat–emtricitabine–TAF moderately increased glecaprevir exposure, but within acceptable limits.

Although it has not been studied, coadministration of glecaprevir plus pibrentasvir with HIV non-nucleoside reverse-transcriptase inhibitors, including efavirenz, etravirine and nevirapine, is not recommended due to drug–drug interactions leading to decreased exposure to glecaprevir and pibrentasvir.

Coadministration of voxilaprevir with HIV antiretrovirals has only been studied in a combination regimen including sofosbuvir and velpatasvir. Coadministration of sofosbuvir plus velpatasvir plus voxilaprevir and HIV protease inhibitors, excluding daily darunavir, is not recommended because of HIV protease inhibition of OATP1B and P-glycoprotein leading to markedly increased exposure to voxilaprevir and moderately increased exposure to sofosbuvir and velpatasvir.

Clinically significant drug–drug interactions are not considered likely with concurrent administration of sofosbuvir plus velpatasvir plus voxilaprevir and daily-dosed darunavir, including when it is boosted with either cobicistat or ritonavir. Concomitant twice-daily darunavir should be used with additional caution and avoided in patients with cirrhosis.

Coadministration of sofosbuvir plus velpatasvir plus voxilaprevir with cobicistat in combination with elvitegravir–emtricitabine–TAF did not lead to any significant changes in exposure to either regimen, but coadministration with cobicistat and atazanavir is not recommended.

Coadministration of HIV non-nucleoside reverse-transcriptase inhibitors and voxilaprevir has not been studied but is not recommended because of CYP3A4 inhibition leading to decreased exposure to sofosbuvir plus velpatasvir plus voxilaprevir. Patients receiving concurrent sofosbuvir plus velpatasvir plus voxilaprevir and TDF should be closely monitored for tenofovir-related adverse effects, such as acute kidney injury and bone mineral density loss.