Article
Managing Drug Interactions in HIV/HCV-Coinfected Patients
Patients taking mediations for both HIV and HCV must be closely monitored for drug-drug interactions.
HIV and hepatitis C virus (HCV) are both serious health concerns, affecting more than 5 million individuals in the United States combined.
Both viruses can result in significant health consequences, especially when left untreated. HIV attacks the body’s immune system, specifically the CD4 cells, which fight off infection. Meanwhile, chronic HCV can lead to serious liver problems, including cirrhosis or liver cancer.
Because of similar transmission routes, HIV/HCV coinfection isn’t uncommon. In fact, about 25% of HIV-infected patients in the United States are coinfected with HCV. Additionally, about 80% of those with HIV who inject drugs also have HCV.
This is a major concern because HIV/HCV-coinfected patients experience more liver-related morbidity and mortality, nonhepatic organ dysfunction, and overall mortality than HCV-monoinfected patients.
Historically, HCV therapy uptake has been lower in the coinfected population due to lower response rates, comorbidities, patient and practitioner perceptions, and poor tolerability to interferon-based therapy. In recent years, however, HCV direct-acting antivirals (DAAs) have scaled some of these barriers.
Recent data suggests HCV/HIV-coinfected patients treated with newer DAA regimens have efficacy rates comparable to those of HCV-monoinfected patients in as little as 12 weeks. However, complex drug interactions between DAAs and antiretroviral therapy (ART) require close awareness and treatment adjustments.
Pharmacists may perform ART switches in collaboration with the HIV practitioner to allow compatibility of DAAs. Alternatively, HCV regimens should be chosen in such a manner that minimizes interactions with ART. Treatment interruption in HIV/HCV-coinfected individuals isn’t recommended.
Here are the major drug interactions for each DAA, with a helpful Table at the end:
Sofosbuvir (Sovaldi)
It’s not metabolized, and it doesn’t induce or inhibit any cytochrome (CYP) P450 enzymes. Drug interaction studies with ART (efavirenz, tenofovir, emtricitabine, rilpivirine, ritonavir-boosted darunavir, and raltegravir) showed no clinically significant interactions. Sofosbuvir isn’t recommended for use with tipranavir because of its potential to induce P-gp.
Ledipasvir/Sofosbuvir (Harvoni)
Ledipasvir undergoes minimal metabolism and doesn’t inhibit or induce CYP enzymes.
Harvoni can be used with most ART, as drug interaction studies didn’t identify clinically significant interactions with abacavir, dolutegravir, emtricitabine, lamivudine, raltegravir, or rilpivirine. Interactions with maraviroc and enfuvirtide wouldn’t be expected based on pharmacologic profiles.
Ledipasvir increases tenofovir levels, which may increase the risk of tenofovir-associated renal toxicity. When given as tenofovir disoproxil fumarate (TDF), concomitant use requires consideration of creatinine clearance (CrCl) rate and should be avoided in those with CrCl <60 mL/min. As this effect increases when TDF is used with ritonavir- or cobicistat-boosted regimens, Harvoni should be avoided with these combinations unless the ART can’t be changed and treatment urgency is high. Alternatively, tenofovir alafenamide (TAF) can be considered in place of TDF in those requiring ritonavir or cobicistat-containing ART.
Sofosbuvir/Velpatasvir (Epclusa)
Velpatasvir is metabolized by CYP3A4, CYP2C8, and CYP2B6. It doesn’t appear to inhibit or induce any CYP enzymes.
Epclusa can be used with most ART, with the exception of efavirenz or etravirine because of reduced exposure of velpatasvir with efavirenz and lack of study with etravirine.
Like ledipasvir, velpatasvir increases tenofovir levels when given as TDF. Concomitant use requires consideration of renal function and should be avoided in those with CrCl <60 mL/min. TAF should be considered in place of TDF in those requiring ritonavir or cobicistat-containing ART.
Paritaprevir/Ritonavir/Ombitasvir Plus Dasabuvir (Viekira Pak)
It has the greatest number of drug interaction among all DAAs. Additionally, ritonavir serves as an HIV protease inhibitor and can thus select for HIV protease inhibitor resistance. As a result, HIV/HCV-coinfected patients should have achieved HIV RNA suppression before initiating Viekira Pak, while those not taking ART should avoid it use.
Ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir are metabolized by, and inhibitors of, CYP3A4 and CYP2C8. The regimen should be avoided with darunavir, efavirenz, ritonavir-boosted lopinavir, ritonavir-boosted tipranavir, etravirine, nevirapine, cobicistat, and rilpivirine. The total daily dose of ritonavir must be carefully considered when using Viekira Pak with ritonavir-boosted HIV protease inhibitors.
Viekira Pak should be used with ART that it doesn’t substantially interact with, including atazanavir, dolutegravir, emtricitabine, enfuvirtide, lamivudine, raltegravir, and tenofovir. The ritonavir dose used for boosting HIV protease inhibitors may need to be adjusted or held when administered with Viekira Pak and then restored when HCV treatment is completed.
Simeprevir (Olysio)
It’s metabolized primarily by CYP3A4 and is therefore susceptible to drug interactions with inhibitors and inducers of this enzyme.
Drug interaction studies with ART showed simeprevir concentrations were reduced when used with efavirenz and substantially increased when dosed with ritonavir-boosted darunavir. Use with efavirenz, etravirine, nevirapine, cobicistat, or boosted HIV protease inhibitors isn’t recommended.
Simeprevir should be used with ART that it doesn’t substantially interact with, including abacavir, emtricitabine, enfuvirtide, lamivudine, maraviroc, raltegravir, dolutegravir, rilpivirine, and tenofovir.
Elbasvir/Grazoprevir (Zepatier)
Both are substrates for CYP3A4 and P-gp, so moderate and strong CYP3A and P-gp inducers (including efavirenz) aren’t recommended for coadministration with Zepatier.
Zepatier is incompatible with all ritonavir-boosted HIV protease inhibitors. Although it hasn’t been studied with etravirine or cobicistat-boosted elvitegravir, drug interactions are expected and these combinations should be avoided.
Zepatier should be used with ART that it doesn’t substantially interact with, including abacavir, emtricitabine, enfuvirtide, lamivudine, raltegravir, dolutegravir, rilpivirine, and tenofovir.
Daclatasvir (Daklinza)
It’s a substrate and a very weak inducer of CYP3A4, so moderate or strong inducers of CYP3A may decrease its plasma levels and therapeutic effect.
When used with moderate CYP3A4 inducers, including efavirenz, etravirine, and nevirapine, the dose should be increased to 90 mg daily. With strong 3A4 inducers, including ritonavir-boosted atazanavir, indinavir, nelfinavir, saquinavir, and cobicistat-containing regimens, Daklinza requires dose reduction to 30 mg daily.
Daclatasvir doesn’t have clinically significant interactions with tenofovir or dolutegravir. Although it hasn’t been studied with emtricitabine, abacavir, rilpivirine, raltegravir, cobicistat-boosted elvitegravir, or maraviroc, substantial interactions aren’t expected based on these agents’ pharmacology.
Ribavirin
It’s contraindicated with didanosine due to an increased risk of mitochondrial toxicity with hepatomegaly and steatosis, pancreatitis, and lactic acidosis. The combined use of ribavirin and zidovudine isn’t recommended due to an increased rate of anemia and the need for ribavirin dose reduction.
Table: Major Drug Interactions Between DAAs and ART
Sovaldi
Harvoni
Epclusa
Viekira Pak
Olysio
Zepatier
Daklinza
Nucleoside Reverse Transcriptase Inhibitors (NRTI)
TDF
√
√
Monitor for TDF toxicity
√
√
√
√
TAF
√
√
√
√
√
√
√
Emtricitabine
√
√
√
√
√
√
√
Lamivudine
√
√
√
√
√
√
√
Abacavir
√
√
√
√
√
√
√
Protease Inhibitors
Atazanavir
(unboosted)
√
√
√
√
↓ ATV dose to 300 mg
X
X
√
Atazanavir*
√
√
If used with TDF, monitor for toxicity
√
√
↓ ATV dose to 300 mg and D/C RTV or COBI in HIV regimen until therapy finished
X
X
√
↓ DCV dose to 30 mg/day
Saquinavir*
√
√
X
X
X
Lopinavir*
√
√
X
X
X
√
Darunavir*
√
√
X
X
X
√
Tipranavir*
X
X
X
X
X
X
?
Non-NRTIs
Efavirenz
√
√
If used with TDF, monitor for toxicity
X
X
X
X
√
↑ DCV dose to 90 mg/day
Etravirine
√
X
X
X
X
Nevirapine
√
√
X
X
X
Rilpivirine
√
√
X
√
√
√
Integrase Inhibitors
Dolutegravir
√
√
If used with TDF, monitor for toxicity
√
√
√
√
√
Raltegravir
√
√
√
√
√
√
√
Stribild
√
√
√
X
X
X
√
↓ DCV dose to 30 mg/day
Genvoya
√
√
√
X
X
X
CCR5 Antagonist
Maraviroc
√
√
√
X
√
√
√
Key:
√ = ART and HCV agents can be used concomitantly
X = Combination not recommended
? = Data limited or not available
* = Ritonavir/cobicistat-boosted regimen
