[12][13] In 2016, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America jointly published a recommendation for the management of hepatitis C. In this recommendation, sofosbuvir used in combination with other drugs is part of all first-line treatments for HCV genotypes 1, 2, 3, 4, 5, and 6, and is also part of some second-line treatments.

[14] Compared to previous treatments, sofosbuvir-based regimens provide a higher cure rate, fewer side effects, and a two- to four-fold reduction in therapy duration.

[20][21] For people who have experienced treatment failure with some form of combination therapy for hepatitis C infection, one of the next possible steps would be retreatment with sofosbuvir and either ledipasvir or daclatasvir, with or without weight-based ribavirin.

[23] It is recommended that sofosbuvir/ribarivin combinations be avoided in pregnant females and their male sexual partners in order to reduce harmful fetal defects caused by ribavirin.

Common side effects are fatigue, headache, nausea, rash, irritability, dizziness, back pain, and anemia.

Sofosbuvir (in combination with ledipasvir, daclatasvir or simeprevir) should not be used with amiodarone due to the risk of abnormally slow heartbeats.

[7] Sofosbuvir is a substrate of P-glycoprotein, a transporter protein that pumps drugs and other substances from intestinal epithelium cells back into the gut.

[27] Sofosbuvir is a prodrug of the Protide type, whereby the active phosphorylated nucleotide is granted cell permeability and oral bioavailability.

[30] Prior to the discovery of sofosbuvir, a variety of nucleoside analogs had been examined as antihepatitis C treatments, but these exhibited relatively low potency.

The design of sofosbuvir, based on the ProTide approach, avoids this slow step by building the first phosphate group into the structure of the drug during synthesis.

[11] Gilead submitted the New Drug Application for sofosbuvir in combination with ribavirin in April 2013, and in October 2013 it received the FDA's Breakthrough Therapy Designation.

[12][13] Following its approval by the FDA in 2013,[34] the price of sofosbuvir as quoted in various media sources in 2014 ranged from $84,000 to $168,000 depending on course of treatment in the U.S.[39] and £35,000 in the United Kingdom for a 12-week regimine,[40] causing considerable controversy.

[49][50][51] In April 2014, U.S. House Democrats Henry Waxman, Frank Pallone Jr., and Diana DeGette wrote Gilead Sciences Inc. questioning the $84,000 price for sofosbuvir.

[55] According to the California Technology Assessment Forum, a panel of academic pharmacoeconomic experts, representatives of managed care organizations, and advocates for people with hepatitis, a 46% discount would bring the average price of treatment to about $40,000, at which price sofosbuvir-based treatment regimens represent a "high value" for people and healthcare systems.

[56][57][58] Because of sofosbuvir's high price in the United States, by 2017, some states—such as Louisiana—were withholding the medicine from Medicaid patients with hepatitis until their livers were severely damaged.

[64] As of 2015, sofosbuvir is included on the list of essential medications in Croatia and its cost is fully covered by the Croatian Health Insurance Fund.

If the office of the controller general of patents had granted it, Gilead would have obtained exclusive rights to produce and sell sofosbuvir in the country.

[66][67] In the meantime, it[clarification needed] granted Indian companies voluntary licenses (VLs), which allowed them to make and sell in a selected few countries at a discounted price.

Gilead also said it would sell a name brand version of the product in India for $300 per course of treatment, approximately double a third party estimate of the minimum achievable cost of manufacture.

[46] The leader of one Indian activist group called this move inadequate,[46] but nine companies launched products, which "unleashed a fierce marketing war", according to India's The Economic Times.

[1] In Egypt, which had the world's highest incidence of hepatitis C, Gilead offered sofosbuvir at the discounted price of $900 to the Egyptian government.

[83] Due to the high cost of sofosbuvir in the U.S., as of 2016 increasing numbers of Americans with hepatitis C were traveling to India to purchase the drug.

Similarly, increasing numbers of Chinese were also traveling to India to purchase sofosbuvir, which had not yet been approved for sale in China by the country's State Food and Drug Administration (SFDA).

[84] Combinations of sofosbuvir with NS5A inhibitors, such as daclatasvir, ledipasvir or velpatasvir, have shown sustained virological response rates of up to 100% in people infected with HCV.

[89] At DEF CON 32, Mixæl Swan Laufer, a representative of the Four Thieves Vinegar Collective, presented a talk titled "Eradicating Hepatitis C with BioTerrorism."

The presentation argued that advancements in open-source tools and chemistry enable individuals to synthesize certain medications, such as Sovaldi, at home, potentially bypassing high pharmaceutical costs.

During the talk, Laufer demonstrated tools and techniques used by the collective to synthesize pharmaceuticals, showcasing examples of the medications created.

To illustrate the efficacy and accessibility of the process, he consumed a dose of Sovaldi onstage, despite not having Hepatitis C, as a symbolic gesture of the drug's claimed safety.