Hepatitis C Virus

Actualizado Reviewed


Prevalence and Incidence Estimates

Hepatitis C virus (HCV) is an enveloped, single-stranded RNA virus of the Flaviviridae family with seven known genotypes and 84 subtypes, with genotypes 1 and 3 being most common worldwide.1-3 It is the most commonly reported bloodborne infection in the United States and is a leading cause of liver-related morbidity and mortality, particularly among people with HIV. In 2019, the estimated global prevalence of chronic HCV infection was 58 million (0.8% of general population), a decline from previous estimates of 71 million in 2015.4 In the United States, updated estimates for 2013 to 2016 are that approximately 4.1 million people were HCV antibody positive (past or current infection; 1.7% of all adults); 2.4 million were HCV RNA positive (current infection; 1% of all adults).5 Comparable data from 2003 to 2010 showed that 4.6 million people were antibody positive and 3.5 million were living with current HCV infection.6 These updated lower prevalence estimates reflect interval trends, including increased cures with new treatment options and increasing death rates due to aging. However, these may be offset by increases in incident cases due to the opioid crisis in vulnerable counties.7,8 Despite variable state-level surveillance practices,9 Centers for Disease Control and Prevention (CDC) surveillance data from 2019 show regional differences in incidence and prevalence, increasing rates in rural areas, ongoing racial/ethnic disparities, and changing demographics, including a bimodal distribution of infections with peaks at 29 years and at 59 years of age.10 Attributable mortality is highly variable among states and counties.11

Given the shared transmission routes between HIV and HCV, estimates of the burden of HCV infection in people with HIV (HIV/HCV coinfection) have been highly variable depending on the comprehensiveness of databases analyzed. A global systematic review and meta-analysis of studies published between 2002 and 2015 estimated that there were 2.3 million cases of coinfection worldwide, with 1.3 million (58%) attributed to persons who inject drugs; this translates to HCV coinfection prevalence of 6.2% among people with HIV.12 Compared with people without HIV, the odds of HCV infection in people with HIV are six times higher. The prevalence of HCV infection among people with HIV is distributed in the following subgroups: people who inject drugs (82.4%), men who have sex with men (MSM, 6.4%), and those who are pregnant or heterosexually exposed (2.4%).12 Estimates of HCV coinfection in the United States10 have been cited as 21% but have ranged from 6% to 30% with high variability based on the distribution of HIV transmission risk factors.13,14 In the United States, it is estimated that 62% to 80% of people who inject drugs who have HIV also have HCV infection.10

The availability of highly effective treatments for HCV infection has led to national and global initiatives aimed at HCV elimination in general and in high-risk persons, such as those with HIV coinfection. The World Health Organization has developed targets for countries to achieve HCV elimination by 2030: diagnosing 90% of those with chronic infection and curing 80% of those diagnosed.4 The CDC Division of Viral Hepatitis 2025 Strategic Plan aims to increase HCV cure to >85% by 2030.15 The use of an HCV cascade of care has shown that there are ongoing gaps to attaining cure encompassing screening, initiating and completing treatment, and preventing reinfection.16,17 Worldwide, 15.2 million (26.2%) out of an estimated 58 million people knew their HCV status by the end of 2019.18 With progress in direct antiviral treatments, 9.4 million people received HCV treatment, with the vast majority cured, between 2015 and 2019.18 Micro-elimination efforts to scale-up treatment as prevention among people with HIV have successfully demonstrated that such efforts can decrease hepatitis C incidence.19-24

Transmission Routes

Both HIV and HCV can be transmitted by percutaneous exposure to blood or blood products, sexual intercourse, and perinatal transmission; however, the relative efficiency of transmission by these routes varies substantially.25 HCV is approximately 10 times more infectious than HIV through percutaneous blood exposures and has been shown to survive for weeks in syringes.26,27 Transmission via injection drug use remains the most common mode of acquisition in the United States, while transmission through contaminated blood products is now rare. Health care–associated transmission of HCV also can occur because of improper reuse of parenteral medications and equipment.28 Other factors that have been associated with HCV infection include accidental occupation-related needlestick injuries, intranasal cocaine use, chronic hemodialysis, and tattoo placement.

Multiple outbreaks of acute HCV infection in MSM demonstrate that sexual transmission is an important mode of acquisition in this population. Risk factors include unprotected receptive anal intercourse, use of sex toys, non-injection recreational drug use, and concurrent sexually transmitted infections (STIs).29-32 Evidence for increasing HCV incidence and prevalence in HIV-negative men seen in HIV pre-exposure prophylaxis (PrEP) clinics has led to current recommendations to monitor for acute HCV infection and routinely test for HCV as part of PrEP care.33-35 Heterosexual transmission of HCV is uncommon but more likely in those whose partners have HIV/HCV coinfection.16,36-38

Perinatal transmission of HCV infection occurs in approximately 7% and 12% of infants born to HCV-seropositive and RNA-positive mothers without and with HIV,39-41 respectively, with possible decreased transmission risk for women with HIV receiving antiretroviral treatment.42

Clinical Manifestations

Both acute and chronic HCV infections are usually minimally symptomatic or asymptomatic. Fewer than 20% of patients with acute infection have characteristic symptoms, including low-grade fever, mild right-upper-quadrant pain, nausea, vomiting, anorexia, dark urine, and jaundice. Unexplained elevations in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels may be the only laboratory finding during acute and chronic infection. Recognition of acute HCV infection in patients with new-onset liver enzyme elevations is clinically important; early initiation of HCV treatment can lower the likelihood of poorer outcomes and prevent transmission to others (treatment as prevention).43-45

Cirrhosis develops in 20 to 40% of patients with chronic HCV infection within 20 years after infection, although the risk for an individual is highly variable.46-48 Risk factors for development of significant liver disease include older age at the time of infection, male sex, obesity, and concomitant alcohol use.47,49 HIV coinfection adversely affects the course of HCV infection, resulting in significantly accelerated progression of liver disease to cirrhosis, particularly in those with advanced immunodeficiency50,51 (CD4 T lymphocyte [CD4] count <200 cells/mm3). Further, coinfected patients with cirrhosis progress more rapidly to life-limiting outcomes—such as end-stage liver disease and hepatocellular carcinoma (HCC)—than those who are HCV mono-infected,52,53 even if they are virally suppressed.54 Because of its high prevalence and accelerated progression, HCV infection was a leading non-AIDS cause of death in people with HIV before the advent of highly effective direct-acting antivirals.55-57 In addition to liver disease, HCV may be associated with symptomatic vasculitis due to cryoglobulinemia (largely affecting the skin or joints), renal disease (membranoproliferative glomerulonephritis), and porphyria cutanea tarda.


On entry into HIV care, all patients should undergo routine HCV screening (AII). Initial testing for HCV should be performed using a U.S. Food and Drug Administration (FDA)-approved immunoassay licensed for detection of antibody to HCV (anti-HCV) in blood.58,59 For at-risk HCV-seronegative individuals, specifically MSM or persons who inject drugs, HCV antibody testing, using an FDA-approved immunoassay, is recommended annually or as indicated by clinical presentation, risk activities, or exposure (AII). Concordantly, both the American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA) HCV guidance and CDC PrEP guidelines also recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and people who inject drugs.59,60 Nucleic acid testing for HCV RNA is recommended in settings where acute infection is suspected or in persons with known prior infection cleared spontaneously or after treatment (AIII).

False-negative anti-HCV antibody results are possible among people with HIV but uncommon (2% to 4%), and more likely to be seen in patients with advanced immunosuppression61 (CD4 cell count <200 cells/ mm3). HCV RNA testing should be performed in those patients with risk factors or unexplained ALT elevation. In addition, negative anti-HCV antibody results can occur during acute infection. Following acute HCV infection, the duration of the window period prior to seroconversion is highly variable, ranging from 2 weeks to more than 24 weeks,62,63 with antibody response in most persons detectable at 8 to 12 weeks. Serum ALT levels are frequently elevated early in the course of HCV infection, and high ALT levels should prompt testing for HCV RNA if serologic test results are negative or indeterminate in individuals at risk of HCV infection.64

Individuals who test positive for HCV antibody should undergo additional diagnostic testing by using a sensitive quantitative assay to measure plasma HCV RNA level and confirm current infection (AI). This should preferentially be done as an automatic reflex to HCV RNA testing of the leftover serum from the blood draw for antibody testing to facilitate diagnosis.65 Reinfection can occur in both seropositive individuals who spontaneously clear their infection or those who achieve a sustained virologic response to treatment. Diagnosing a new active infection will require HCV RNA testing in such individuals (AII).

Preventing Exposure

The primary route of HCV transmission is blood-to-blood contact, most commonly from sharing drug-injection equipment or paraphernalia (i.e., “cookers,” filters, or water) previously used by an infected person with HCV. Prevention approaches for persons who inject drugs include harm-reduction encompassing opioid agonist therapy and syringe services programs to avoid the reuse or sharing of syringes, needles, water, cotton, and other drug preparation equipment.66,67 Both needle and syringe exchange programs and opioid substitution therapy have been shown to reduce the risk of HCV acquisition in people who inject drugs.67,68 HCV also can be transmitted sexually, especially among MSM with HIV.69 Risk factors for sexual HCV acquisition include unprotected anal receptive intercourse, fisting, sharing of sex toys, ulcerative STIs, and use of methamphetamine or other sex-enhancing drugs (injection or otherwise).70,71

Patients should be counseled regarding the risk of sexual HCV acquisition (AII). Those with multiple sex partners or STIs should be advised to use barrier protection to reduce their risk of STIs including hepatitis C infection (AII).

Preventing Disease

There is no available vaccine or recommended post-exposure prophylaxis to prevent HCV infection.72,73 Following acute HCV infection, chronic infection can be prevented within the first 6 to 12 months after infection through antiviral treatment; high rates of viral clearance have been observed with HCV treatment during the acute phase of infection.74,75

Because most patients with acute HCV infection may transmit to others and are at risk for loss to follow-up, immediate treatment with the same regimens recommended for chronic HCV should be offered (AIII).44,76 Specific treatment regimens in acute infection are the same as those recommended for chronic HCV infection and are detailed in the Treating HCV section.

People with HCV infection should be tested for previous or concurrent hepatitis B virus (HBV) infection because coinfection with HBV is associated with increased morbidity (AII). Those without evidence of immunity to HBV infection should be vaccinated (see the Hepatitis B Virus Infection section) (AII). Likewise, because acute hepatitis A virus (HAV) infection is more likely to be fulminant in persons with HCV infection,77 these patients should be screened for immunity (HAV immunoglobulin G or antibody total) and non-immune persons should be vaccinated (AII).

People with HCV infection should be counseled about methods to prevent liver damage by avoiding any alcohol consumption (because alcohol accelerates progression of liver disease), limiting ingestion of potentially hepatotoxic medications (e.g., acetaminophen should be limited to <2 g/day for those with acute infection or bridging fibrosis/cirrhosis), and avoiding iron supplementation in the absence of documented iron deficiency.78

People with HIV/HCV coinfection with cirrhosis are at risk of life-threatening complications and should be managed in consultation with a gastroenterologist or hepatologist. In particular, individuals with cirrhosis should undergo serial screening for HCC; current guidelines recommend performing ultrasonography at 6‑month intervals, although the optimal screening strategy is unknown (AIII).79 Because of its relatively poor specificity and sensitivity, serum alfa-fetoprotein is an adjunct to ultrasonography but should not be the sole screening method.79 HIV infection is not a contraindication to liver transplantation; accordingly, coinfected patients with decompensated liver disease and/or early HCC may be considered for transplantation at specialized transplant centers.

Although earlier studies focused on the potential for antiretroviral (ARV)-associated liver injury with certain agents, more recent studies have found that effective HIV treatment is associated with reduced risk of liver disease progression, though not to levels of persons with HCV infection without HIV.54,80 Coinfected patients should be treated in accordance with the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV.

Treating HCV Infection


Direct-acting antiviral (DAA) regimens for HCV infection have become standardized with one of two pangenotypic, highly efficacious and well-tolerated antiviral treatment regimens, which are the preferred therapy for HCV infection for almost all persons with HIV and HCV. Clinicians can refer to the most recent AASLD/IDSA HCV treatment guidance.

The goals of therapy, treatment regimen, and monitoring parameters for patients with HIV/HCV coinfection are similar to those recommended for patients with HCV mono-infection. However, people with HIV were historically considered a “special population” with regard to HCV treatment. This designation was rooted in inferior responses to interferon-based treatment for those with HIV.81,82 The arrival of initial DAA regimens narrowed the gap in response to treatment but continued to present significant drug–drug interaction considerations and, in some circumstances, warrant extended treatment durations.

Simplified approaches to HCV treatment have emerged as a means to facilitate treatment by non-specialist providers and increase treatment uptake for the majority of persons with HCV infection. In general, simplified approaches to HCV treatment apply to treatment-naive persons without cirrhosis and encompass minimal baseline testing (with omission of genotype), standardized treatment approaches using pangenotypic regimens, no on-treatment testing or in-person follow-up, and limited follow-up to confirm sustained virologic response (SVR).

Several factors now allow the inclusion of people with HIV in simplified HCV treatment recommendations. The emergence of unboosted integrase strand transfer inhibitor (INSTI)-based ARV regimens has eliminated clinically significant drug interactions with current first-line DAA regimens. Additionally, the improved safety profile of tenofovir alafenamide (TAF) combined with safety data in the setting of boosted ARV regimens during coadministration with DAAs obviate the need for enhanced toxicity monitoring for people with HIV in most instances. Finally, accumulation of clinical efficacy data and the necessity of expanding treatment access support the use of simpler standardized treatment approaches initially validated in HCV mono-infected populations for those with HIV. Based on these developments and the emergence of pangenotypic DAA regimens, treatment of HCV can be approached using simplified protocols for the majority of people with HIV.

Published clinical trial data directly support a simplified approach to HCV treatment, including for people with HIV. The AIDS Clinical Trial Groups (ACTG) A5360 study (MINMON) evaluated an approach consisting of limited baseline testing and supply of the entire 84-tablet (12-week) sofosbuvir/velpatasvir treatment regimen in 399 participants, including 166 with HIV.83 All participants were HCV treatment-naive, compensated cirrhosis was allowed, and no pre-treatment HCV genotyping was performed. No on-study laboratory monitoring or in-person follow-up was conducted. The SVR after 12 weeks post-treatment (SVR12) was 95% overall (95% CI, 92.4% to 96.7%) and 95% in the subset of people with HIV (157/166).

The SMART-C study randomized participants to either a standard 8-week treatment with glecaprevir/pibrentasvir (n = 127), which included in-person follow-up at weeks 4 and 8 with medication refill required at week 4, or to a simplified approach (n = 253) that omitted the on-treatment visits with all medication dispensed at initiation.84 Persons with previous HCV treatment or cirrhosis were excluded and only a small number of people with HIV (n = 27) were included. A modified intention-to-treat analysis (excluding lost to follow-up and missing SVR12 results) established non-inferiority of the simplified approach with SVR12 of 97% (233/241) compared with 98% (121/123) in the standard-approach arm. No difference in response was seen by HIV status.

Staging and Monitoring

While a pre-HCV treatment assessment of patient readiness for therapy should be completed, with an indication that reasonable adherence can be expected, HCV DAA therapy should not be withheld solely due to perceived lack of adherence with HIV therapy or untreated HIV infection (BIII). Evidence suggests the level of adherence needed for HCV cure is more modest than that required to maintain HIV viral suppression.85-87 In addition, despite a lack of HIV control, patients may be uniquely motivated by the potential for HCV cure, thereby increasing the likelihood of successful treatment.

Additional fibrosis stage assessment may be indicated in people with HIV with an indeterminate FIB-4 (1.45–3.25) score, particularly if cirrhosis is suspected (BIII). Additional blood- or serum-based assays for fibrosis staging are not recommended because they provide little benefit over FIB-‍4 (BII).88,89

Non-invasive ultrasound-based (e.g., shear wave elastography or vibration controlled transient elastography) or imaging-based (e.g., magnetic resonance elastography) modalities are recommended if available (BII). Liver biopsy is no longer recommended for liver fibrosis staging related to HCV infection unless there is another indication to obtain one (AII). Treatment should not be withheld if access to additional staging modalities is not readily available (AIII).

Simplified Approach to HCV Treatment

The current AASLD/IDSA HCV guidance for simplified HCV treatment of treatment-naive adults (without cirrhosis or with compensated cirrhosis) excludes persons with HIV. The Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV recommends an approach that allows most people with HIV to qualify for simplified HCV treatment. This simplified approach is appropriate except in certain people with HIV with conditions noted in Box 1. Such exclusions highlight the importance of particular ARV regimens with significant drug–drug interactions with ARVs (see below).

Box 1. Characteristics of People with HIV for Whom Simplified Hepatitis C Virus Treatment Is Not Recommendeda
  1. Prior HCV treatment (Reinfection after prior successful therapy is not an exclusion.)
  2. Decompensated cirrhosisb
  3. TDF-containing regimen with an eGFR <60mL/min
  4. On efavirenz, etravirine, nevirapine, or boosted HIV-1 protease inhibitorsc
  5. Untreated chronic HBV infection
  6. Pregnancy
a People with HIV and HCV infection who meet these exclusion criteria should be treated for HCV following standard approaches (see the AASLD/IDSA HCV Guidance).

b Including, but not limited to, current or prior variceal bleeding, ascites, or hepatic encephalopathy

c People with HIV on boosted protease inhibitors are not eligible for treatment with glecaprevir/pibrentasvir and may require on-treatment monitoring.
Key: eGFR = estimated glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; TDF = tenofovir disoproxil fumarate

A limited pre-treatment assessment for people with HIV is essentially the same as for people without HIV who qualify for a simplified approach (Box 2) (AIII). Key components are documentation of active HCV infection and initial assessment of liver fibrosis stage. Determination of HCV genotype prior to treatment is not necessary in treatment-naive patients, with the exception of persons with compensated cirrhosis who are planned for treatment with sofosbuvir/velpatasvir. In this case, if genotype 3 HCV infection is identified, additional testing for resistance-associated substitution (RASs) is required before treatment with sofosbuvir/velpatasvir. Notably, HIV parameters (i.e., HIV RNA or CD4 count) are not required to determine eligibility for a simplified approach. The efficacy of HCV DAA treatment for people does not appear to be compromised at lower CD4 counts.90-92

Box 2. Pre-treatment Assessment Under Simplified Approach
  1. Creatinine, liver function tests, and complete blood count
  2. HCV RNA
  3. Hepatitis B surface antigen
  4. Initial fibrosis staging with FIB-4 (FIB-4 calculator)a
  5. Medication and drug interaction review
  6. HCV genotype required if cirrhosis is present
a Additional testing may be required if results are indeterminate (see text).

Key: HCV = hepatitis C virus

Drug–Drug Interactions

Drug interactions with ARVs pose less of a constraint on DAA use to treat HCV infection in people with HIV given the prominence of unboosted INSTI and TAF among first-line ARV regimens.93 A comprehensive review of drug interactions between ARVs and antivirals for hepatitis C can be found within the Hepatitis C Virus/HIV Coinfection section of the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Interactions of clinical significance pertaining to the recommended DAA regimens are highlighted here and in Table 4.

Efavirenz coadministration results in a significant decrease in glecaprevir, pibrentasvir, and velpatasvir exposures.94,95 People with HIV on an efavirenz-containing regimen are not eligible for simplified DAA treatment approaches (Box 1) and generally require an ARV switch prior to DAA treatment (AII).

Given similar pharmacologic profiles, including cytochrome P450 (CYP) enzyme induction, nevirapine and etravirine are also not recommended for coadministration with HCV DAAs, including glecaprevir/pibrentasvir and sofosbuvir/velpatasvir (AII).

Ritonavir- or cobicistat-boosted protease inhibitors significantly increase glecaprevir and pibrentasvir exposure94; people with HIV on boosted protease inhibitor (PI)–based ARV regimens were not included in registrational trials of glecaprevir/pibrentasvir and coadministration is not recommended (BII).96 Boosted protease inhibitors also increase velpatasvir exposure, which in turn increases tenofovir plasma exposure particularly when administered as TDF.95 People with HIV on boosted ARV regimens were included in sofosbuvir/velpatasvir registrational trials, and the combination was not associated with increased adverse events.97

Given these considerations, sofosbuvir/velpatasvir can be co-administered with boosted ARV regimens (AII); TAF-based regimens are preferred. People on TDF-containing boosted ARV regimens are not eligible for simplified HCV treatment if their estimated glomerular filtration rate is <60 mL/min because monitoring on treatment is recommended (AII).

Summary of Major Drug Interactions Between HIV and HCV Antivirals
HIV Antivirals Glecaprevir/Pibrentasvir Sofosbuvir/Velpatasvir
EFV, ETR, NVP, and other strong CYP 3A4 and P-gp inducers Significant decrease in glecaprevir and pibrentasvir concentrations
Significant decrease in velpatasvir concentrations
PI/r, PI/c, unboosted ATV Significant increase in glecaprevir and pibrentasvir concentrations

Boosted PIs may increase velpatasvir concentrations, but no significant adverse events in clinical trial

Coadministration allowed

TDF, TAF Coadministration allowed

TAF preferred

If TDF is used with boosted PIs if GFR <60 mL/min, monitoring is recommended.

RPV, DOR, EVG/c, RAL, BIC, DTG, ABC, FTC, 3TC, MVC Coadministration allowed Coadministration allowed
Key: 3TC = lamivudine; ABC = abacavir; ATV = atazanavir; BIC = bictegravir; CYP = cytochrome P450; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG/c = elvitegravir/cobicistat; GFR = glomerular filtration rate; FTC = emtricitabine; MVC = maraviroc; NVP = nevirapine; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; P-gp = p-glycoprotein; RAL = raltegravir; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

HCV Treatment Regimens

In HCV treatment-naive persons without cirrhosis, the recommended DAA regimens are either—

  • Glecaprevir/pibrentasvir fixed dose combination (FDC) (100-mg/40-mg tablet), three tablets daily for 8 weeks (AI)


  • Sofosbuvir/velpatasvir FDC (400-mg/100-mg tablet), one tablet daily for 12 weeks (AI)

As noted in Box 1, these recommendations do not apply to HCV treatment–experienced patients because some of these individuals may require other DAA combinations and/or consultation with an expert. Persons meeting other criteria listed in Box 1 should be treated according to standard approaches. Clinicians can refer to the most recent HCV treatment guidance for recommendations.

Primary data supporting the efficacy and safety of the two recommended treatment regimens in people with HIV come from registrational trials. In the ASTRAL-5 study, 12 weeks of sofosbuvir/velpatasvir without ribavirin was given to 106 people with HIV, including 19 with cirrhosis.97 The SVR12 was 95% by intention-to-treat analysis with only two of five failures due to confirmed viral relapse. All participants with cirrhosis were cured. The EXPEDITION-2 study evaluated glecaprevir/pibrentasvir 300 mg/120 mg in 153 people with HIV with duration determined by cirrhosis status, with 137 non-cirrhotic participants treated for 8 weeks and 16 with cirrhosis treated for 12 weeks.96 By intention-to-treat analysis, SVR12 was 98%, including 135 out of 137 participants without cirrhosis and 15 out of 16 participants with cirrhosis. The only confirmed virologic failure was virologic breakthrough at week 8 in a participant with genotype 3 and cirrhosis. Both regimens were well tolerated with low rates of discontinuation and no severe treatment-associated adverse events.

If compensated cirrhosis is present and sofosbuvir/velpatasvir is the planned regimen, then pre-treatment HCV genotyping is recommended (AII). If HCV genotype 3 is identified, NS5A resistance testing and modification of the sofosbuvir/velpatasvir regimen or selection of an alternative therapy may be necessary (for a full discussion, see the HCV treatment guidance). For all other genotypes or if glecaprevir/pibrentasvir is being used (regardless of genotype), no modification to the treatment regimen is required in the setting of compensated cirrhosis (AIII). The lower-strength recommendation for use of 8 weeks of glecaprevir/pibrentasvir in the setting of cirrhosis stems from a lack of prospective trials evaluating this duration in people with HIV and cirrhosis; 12 weeks of glecaprevir/pibrentasvir may be used in this setting (CI). The EXPEDITION-8 trial evaluated 8 weeks of glecaprevir/pibrentasvir in 343 participants with compensated cirrhosis and without HIV.98 The intention-to-treat SVR12 was 98% and >99% in a per protocol analysis. The lone virologic failure was in genotype 3 infection yielding a per protocol SVR12 in this group of 98% (60/61). Data from real-world experience of use of 8 weeks of glecaprevir/pibrentasvir in the setting of cirrhosis were recently presented and included a small number of people with HIV.99 Of the 20 people with HIV treated for 8 weeks, 19 out of 20 achieved SVR with no confirmed virologic failures.

Specific Treatment Situations

Acute HCV Infection Treatment

People with HIV are at risk for acute HCV infection. Given the public health implications in reducing onward transmission, in addition to benefit for the individual, HCV treatment should be started as soon as possible in this population (AIII).21,44,100 The simplified treatment regimens outlined above are recommended in acute HCV infection (AII); shorter durations of therapy are currently being investigated. Patients who achieve viral clearance either spontaneously or after treatment should be counseled about the potential for reinfection.

Prior DAA Failure Retreatment

Despite the high cure rates associated with current DAA regimens, the large number of DAA treatments will inevitably result in an appreciable number of DAA failures. Persons with HIV were not included in the registrational trial of sofosbuvir/velpatasvir/voxilaprevir for retreatment of HCV infection101; nor were they included in initial prospective trials of either glecaprevir/pibrentasvir or sofosbuvir plus glecaprevir/pibrentasvir for HCV treatment of prior NS5A inhibitor containing DAA failures.102,103 A follow-up prospective study comparing 12 weeks versus 16 weeks of glecaprevir/pibrentasvir for genotype 1 sofosbuvir plus NS5A inhibitor failures did include a small number of people with HIV (~5%).104 Similarly, published real-world experiences with retreatment of prior DAA failures are underrepresented with respect to people with HIV (all <5% except one with 15%).105-108

Drawing on the experience with initial DAA therapy of HCV infection, where people with HIV have nearly identical outcomes to persons with HCV infection alone, treatment approaches for DAA failures should be the same as those for persons with HCV mono-infection (AIII). Clinicians should refer to the most recent HCV treatment guidance for up-to-date recommendations.

Laboratory Monitoring and Post-Treatment Follow-Up

Laboratory monitoring while on treatment is not required for patients qualifying for the simplified treatment approach. However, documentation of HCV RNA levels at week 4 of therapy may be required by some payors prior to providing additional refills needed to complete therapy.

Effort should be made to document SVR (HCV RNA less than lower limits of quantification) at least 12 weeks after completion of therapy (AI). Patients without cirrhosis who achieve SVR do not require continued liver disease monitoring.

Periodic assessment for HCV reinfection should be done via HCV RNA testing on an at least yearly basis for those with ongoing risk behaviors or more frequently as dictated by clinical circumstances (e.g., new STI diagnosis or elevated liver enzymes) (AII).

In the setting of cirrhosis, hepatocellular carcinoma screening with liver ultrasound every 6 months should continue indefinitely (BII).

Special Considerations During Pregnancy

Pregnant individuals, including those with HIV, should be tested for HCV infection to allow appropriate management for the mothers during pregnancy and after delivery and also to ensure their infants are identified as at risk for transmission and monitored (AIII).109

The rate of perinatal transmission has been reported at approximately 7% for infants born to mothers without HIV and 12% for infants born to mothers with HIV.35,39,110 Due in large part to the opioid epidemic, more infants are born today to pregnant people with HCV infection than ever before111,112; thus, universal screening for pregnant people during each pregnancy, regardless of HIV status, is now the standard of care.113 For the care of the infant, knowledge of exposure risk allows for screening for perinatal transmission.114 For the pregnant person, harm-reduction counseling and linkage to HCV care and treatment are important.115

Assessments for liver disease stage can be delayed until pregnancy related and postpartum changes have resolved. Individuals with known cirrhosis are at higher risks of complications during pregnancy, both for the individual and their infant. Hepatitis A and hepatitis B vaccines can be administered during pregnancy, and individuals who have not previously been vaccinated should receive them (AII).

Data are limited regarding the role of medical or surgical interventions to reduce the risk of perinatal HCV transmission. Nearly all studies, including those in individuals with and without HIV, have found that elective cesarean delivery does not reduce the risk of perinatal HCV transmission.116-119 Moreover, there is an increased risk of maternal morbidity associated with cesarean compared with vaginal delivery, particularly in the setting of maternal HIV infection.120-123 Thus, while elective cesarean delivery in individuals with HIV/HCV coinfection can be considered based on HIV-related indications, data do not support its routine use for the prevention of HCV transmission.

The current standard of care for treatment of HCV infection, regardless of duration, is DAA combination therapy. In real-world studies, SVR rates are similar to those from registration trials,124,125 and are consistently >90%. DAAs have not been sufficiently studied in pregnant women with HCV infection. In a pilot study of ledipasvir/sofosbuvir in pregnant women (without HIV), treatment was started in the end of the second/beginning of the third trimester and found to be safe and resulted in cure in nine women.126 Pharmacokinetic measurements did not identify clinically significant changes.

Historically, while not studied in this population, DAA drugs have not demonstrated significant fetal toxicity concerns in animal studies, in contrast to when interferon and ribavirin were the standard of care. Interferon is no longer used for the treatment of HCV infection and ribavirin is used infrequently and usually in complex treatment or retreatment scenarios. Ribavirin is an FDA category X drug because of its teratogenicity at low doses in multiple animal species. Defects noted in animals include limb abnormalities, craniofacial defects, exencephaly, and anophthalmia.

Ribavirin should not be used during pregnancy (AII). Women of childbearing potential and men receiving ribavirin should be counseled about the risks and need for consistent contraceptive use during and for 6 months after completion of ribavirin therapy (AIII). Inadvertent pregnancy during paternal exposure was not associated with adverse events in two newborns.127 For now, treatment with DAA during pregnancy is not recommended (CIII); more safety data are needed.


  1. Davis C, Mgomella GS, da Silva Filipe A, et al. Highly diverse hepatitis C strains detected in Sub-Saharan Africa have unknown susceptibility to direct-acting antiviral treatments. Hepatology. 2019;69(4):1426-1441. Available at: https://pubmed.ncbi.nlm.nih.gov/30387174.
  2. Smith DB, Bukh J, Kuiken C, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59(1):318-327. Available at: https://pubmed.ncbi.nlm.nih.gov/24115039.
  3. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77-87. Available at: https://pubmed.ncbi.nlm.nih.gov/25069599.
  4. World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. Towards ending viral hepatitis. World Health Organization. 2016. Available at: https://apps.who.int/iris/handle/10665/246177.
  5. Hofmeister MG, Rosenthal EM, Barker LK, et al. Estimating prevalence of hepatitis C virus infection in the United States, 2013–2016. Hepatology. 2019;69(3):1020-1031. Available at: https://pubmed.ncbi.nlm.nih.gov/30398671.
  6. Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160(5):293-300. Available at: https://pubmed.ncbi.nlm.nih.gov/24737271.
  7. Zibbell JE, Iqbal K, Patel RC, et al. Increases in hepatitis C virus infection related to injection drug use among persons aged ≤30 years - Kentucky, Tennessee, Virginia, and West Virginia, 2006–2012. MMWR Morb Mortal Wkly Rep. 2015;64(17):453-458. Available at: https://pubmed.ncbi.nlm.nih.gov/25950251.
  8. Van Handel MM, Rose CE, Hallisey EJ, et al. County-level vulnerability assessment for rapid dissemination of HIV or HCV infections among persons who inject drugs, United States. J Acquir Immune Defic Syndr. 2016;73(3):323-331. Available at: https://pubmed.ncbi.nlm.nih.gov/27763996.
  9. Rosenberg ES, Rosenthal EM, Hall EW, et al. Prevalence of hepatitis C virus infection in U.S. states and the District of Columbia, 2013 to 2016. JAMA Netw Open. 2018;1(8):e186371. Available at: https://pubmed.ncbi.nlm.nih.gov/30646319.
  10. Centers for Disease Control and Prevention. 2019 viral hepatitis surveillance report. 2019. Available at: https://www.cdc.gov/hepatitis/statistics/2019surveillance/index.htm.
  11. Hall EW, Schillie S, Vaughan AS, et al. County-level variation in hepatitis C virus mortality and trends in the United States, 2005–2017. Hepatology. 2021;74(2):582-590. Available at: https://pubmed.ncbi.nlm.nih.gov/33609308.
  12. Platt L, Easterbrook P, Gower E, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016;16(7):797-808. Available at: https://pubmed.ncbi.nlm.nih.gov/26922272.
  13. Bosh KA, Coyle JR, Hansen V, et al. HIV and viral hepatitis coinfection analysis using surveillance data from 15 U.S. states and two cities. Epidemiol Infect. 2018;146(7):920-930. Available at: https://pubmed.ncbi.nlm.nih.gov/29636119.
  14. Prussing C, Chan C, Pinchoff J, et al. HIV and viral hepatitis co-infection in New York City, 2000–2010: prevalence and case characteristics. Epidemiol Infect. 2015;143(7):1408-1416. Available at: https://pubmed.ncbi.nlm.nih.gov/25170631.
  15. Centers for Disease Control and Prevention. About the Division of Viral Hepatitis. 2021. Available at: https://www.cdc.gov/hepatitis/aboutus.htm.
  16. Yehia BR, Schranz AJ, Umscheid CA, Lo Re V, 3rd. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One. 2014;9(7):e101554. Available at: https://pubmed.ncbi.nlm.nih.gov/24988388.
  17. Zuckerman A, Douglas A, Nwosu S, Choi L, Chastain C. Increasing success and evolving barriers in the hepatitis C cascade of care during the direct acting antiviral era. PLoS One. 2018;13(6):e0199174. Available at: https://pubmed.ncbi.nlm.nih.gov/29912944.
  18. World Health Organization. Hepatitis C. 2021. Available at: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c.
  19. Berenguer J, Rodríguez-Castellano E, Carrero A, et al. Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection. Hepatology. 2017;66(2):344-356. Available at: https://pubmed.ncbi.nlm.nih.gov/28109003.
  20. Boerekamps A, Newsum AM, Smit C, et al. High treatment uptake in human immunodeficiency virus/hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands. Clin Infect Dis. 2018;66(9):1352-1359. Available at: https://pubmed.ncbi.nlm.nih.gov/29186365.
  21. Boerekamps A, van den Berk GE, Lauw FN, et al. Declining hepatitis C virus (HCV) incidence in Dutch human immunodeficiency virus-positive men who have sex with men after unrestricted access to HCV therapy. Clin Infect Dis. 2018;66(9):1360-1365. Available at: https://pubmed.ncbi.nlm.nih.gov/29186320.
  22. Doyle JS, van Santen DK, Iser D, et al. Microelimination of hepatitis C among people with human immunodeficiency virus coinfection: declining incidence and prevalence accompanying a multicenter treatment scale-up trial. Clin Infect Dis. 2021;73(7):e2164-e2172. Available at: https://pubmed.ncbi.nlm.nih.gov/33010149.
  23. Liu CH, Kao JH. Last mile to microelimination of hepatitis C virus infection among people living with human immunodeficiency virus. Clin Infect Dis. 2021;73(7):e2172-e2174. Available at: https://pubmed.ncbi.nlm.nih.gov/33005954.
  24. Smit C, Boyd A, Rijnders BJA, et al. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study. Lancet HIV. 2021;8(2):e96-e105. Available at: https://pubmed.ncbi.nlm.nih.gov/33357835.
  25. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13(17):2436-2441. Available at: https://pubmed.ncbi.nlm.nih.gov/17552026.
  26. Paintsil E, He H, Peters C, Lindenbach BD, Heimer R. Survival of hepatitis C virus in syringes: implication for transmission among injection drug users. J Infect Dis. 2010;202(7):984-990. Available at: https://pubmed.ncbi.nlm.nih.gov/20726768.
  27. Sulkowski MS, Moore RD, Mehta SH, Chaisson RE, Thomas DL. Hepatitis C and progression of HIV disease. JAMA. 2002;288(2):199-206. Available at: https://pubmed.ncbi.nlm.nih.gov/12095384.
  28. Prati D. Transmission of hepatitis C virus by blood transfusions and other medical procedures: a global review. J Hepatol. 2006;45(4):607-616. Available at: https://pubmed.ncbi.nlm.nih.gov/16901579.
  29. Cotte L, Hocqueloux L, Lefebvre M, et al. Microelimination or not? The changing epidemiology of human immunodeficiency virus-hepatitis C virus coinfection in France 2012–2018. Clin Infect Dis. 2021;73(9):e3266-e3274. Available at: https://pubmed.ncbi.nlm.nih.gov/33400777.
  30. Crespo J, Cuadrado A, Perelló C, et al. Epidemiology of hepatitis C virus infection in a country with universal access to direct-acting antiviral agents: data for designing a cost-effective elimination policy in Spain. J Viral Hepat. 2020;27(4):360-370. Available at: https://pubmed.ncbi.nlm.nih.gov/31755634.
  31. Liu L, Wang L, Zhang H, et al. Changing epidemiology of hepatitis B virus and hepatitis C virus coinfection in a human immunodeficiency virus-positive population in China: results from the Third and Fourth Nationwide Molecular Epidemiologic Surveys. Clin Infect Dis. 2021;73(4):642-649. Available at: https://pubmed.ncbi.nlm.nih.gov/34398954.
  32. van de Laar TJ, Matthews GV, Prins M, Danta M. Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection. AIDS. 2010;24(12):1799-1812. Available at: https://pubmed.ncbi.nlm.nih.gov/20601854.
  33. Hoornenborg E, Achterbergh RCA, Schim van der Loeff MF, et al. MSM starting preexposure prophylaxis are at risk of hepatitis C virus infection. AIDS. 2017;31(11):1603-1610. Available at: https://pubmed.ncbi.nlm.nih.gov/28657964.
  34. Krakower DS, Mayer KH. Routine screening for hepatitis C in MSM on HIV PrEP. Nat Rev Urol. 2019;16(5):272-274. Available at: https://pubmed.ncbi.nlm.nih.gov/30783262.
  35. Ades AE, Gordon F, Scott K, et al. Overall vertical transmission of HCV, transmission net of clearance, and timing of transmission. Clin Infect Dis. 2022. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35403676.
  36. Eyster ME, Alter HJ, Aledort LM, Quan S, Hatzakis A, Goedert JJ. Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Ann Intern Med. 1991;115(10):764-768. Available at: https://pubmed.ncbi.nlm.nih.gov/1656825.
  37. Lissen E, Alter HJ, Abad MA, et al. Hepatitis C virus infection among sexually promiscuous groups and the heterosexual partners of hepatitis C virus infected index cases. Eur J Clin Microbiol Infect Dis. 1993;12(11):827-831. Available at: https://pubmed.ncbi.nlm.nih.gov/7509282.
  38. Terrault NA, Dodge JL, Murphy EL, et al. Sexual transmission of hepatitis C virus among monogamous heterosexual couples: the HCV partners study. Hepatology. 2013;57(3):881-889. Available at: https://pubmed.ncbi.nlm.nih.gov/23175457.
  39. Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis. 2014;59(6):765-773. Available at: https://pubmed.ncbi.nlm.nih.gov/24928290.
  40. Terrault NA, Levy MT, Cheung KW, Jourdain G. Viral hepatitis and pregnancy. Nat Rev Gastroenterol Hepatol. 2021;18(2):117-130. Available at: https://pubmed.ncbi.nlm.nih.gov/33046891.
  41. Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women. Hepatology. 2000;31(3):751-755. Available at: https://pubmed.ncbi.nlm.nih.gov/10706568.
  42. Domínguez-Rodríguez S, Prieto L, Fernández McPhee C, et al. Perinatal HCV transmission rate in HIV/HCV coinfected women with access to ART in Madrid, Spain. PLoS One. 2020;15(4):e0230109. Available at: https://pubmed.ncbi.nlm.nih.gov/32271775.
  43. Zelenev A, Li J, Mazhnaya A, Basu S, Altice FL. Hepatitis C virus treatment as prevention in an extended network of people who inject drugs in the USA: a modelling study. Lancet Infect Dis. 2018;18(2):215-224. Available at: https://pubmed.ncbi.nlm.nih.gov/29153265.
  44. Bethea ED, Chen Q, Hur C, Chung RT, Chhatwal J. Should we treat acute hepatitis C? A decision and cost-effectiveness analysis. Hepatology. 2018;67(3):837-846. Available at: https://pubmed.ncbi.nlm.nih.gov/29059461.
  45. Rockstroh JK, Boesecke C. Hepatitis C virus treatment as prevention: challenges and opportunities in men who have sex with men. J Infect Dis. 2020;222(Suppl 9):S782-s788. Available at: https://pubmed.ncbi.nlm.nih.gov/33245348.
  46. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332(22):1463-1466. Available at: https://pubmed.ncbi.nlm.nih.gov/7739682.
  47. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349(9055):825-832. Available at: https://pubmed.ncbi.nlm.nih.gov/9121257.
  48. Koretz RL, Abbey H, Coleman E, Gitnick G. Non-A, non-B post-transfusion hepatitis. Looking back in the second decade. Ann Intern Med. 1993;119(2):110-115. Available at: https://www.ncbi.nlm.nih.gov/pubmed/8512159.
  49. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Elevated liver enzymes following initiation of antiretroviral therapy. JAMA. 2000;283(19):2526-2527. Available at: https://pubmed.ncbi.nlm.nih.gov/10815113.
  50. Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology. 1999;30(4):1054-1058. Available at: https://pubmed.ncbi.nlm.nih.gov/10498659.
  51. Di Martino V, Rufat P, Boyer N, et al. The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study. Hepatology. 2001;34(6):1193-1199. Available at: https://pubmed.ncbi.nlm.nih.gov/11732009.
  52. Pineda JA, Romero-Gómez M, Díaz-García F, et al. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology. 2005;41(4):779-789. Available at: https://pubmed.ncbi.nlm.nih.gov/15800956.
  53. Ragni MV, Eghtesad B, Schlesinger KW, Dvorchik I, Fung JJ. Pretransplant survival is shorter in HIV-positive than HIV-negative subjects with end-stage liver disease. Liver Transpl. 2005;11(11):1425-1430. Available at: https://pubmed.ncbi.nlm.nih.gov/16237709.
  54. Lo Re V, 3rd, Kallan MJ, Tate JP, et al. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study. Ann Intern Med. 2014;160(6):369-379. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24723077.
  55. Salmon-Ceron D, Lewden C, Morlat P, et al. Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol. J Hepatol. 2005;42(6):799-805. Available at: https://pubmed.ncbi.nlm.nih.gov/15973779.
  56. Weber R, Sabin CA, Friis-Møller N, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166(15):1632-1641. Available at: https://pubmed.ncbi.nlm.nih.gov/16908797.
  57. Smith JA, Aberle JH, Fleming VM, et al. Dynamic coinfection with multiple viral subtypes in acute hepatitis C. J Infect Dis. 2010;202(12):1770-1779. Available at: https://pubmed.ncbi.nlm.nih.gov/21067369.
  58. Centers for Disease Control and Prevention. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62(18):362-365. Available at: https://pubmed.ncbi.nlm.nih.gov/23657112.
  59. American Association for the Study of Liver Diseases IDSoA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2021. Available at: https://www.hcvguidelines.org.
  60. Centers for Disease Control and Prevention. HIV guidelines: preventing new HIV infections. Available at: https://www.cdc.gov/hiv/guidelines/preventing.html.
  61. Chamie G, Bonacini M, Bangsberg DR, et al. Factors associated with seronegative chronic hepatitis C virus infection in HIV infection. Clin Infect Dis. 2007;44(4):577-583. Available at: https://pubmed.ncbi.nlm.nih.gov/17243063.
  62. Mattsson L, Grillner L, von Sydow M, Bergdahl S, Weiland O. Seroconversion to hepatitis C virus antibodies in patients with acute posttransfusion non-A, non-B hepatitis in Sweden. Infection. 1991;19(5):309-312. Available at: https://www.ncbi.nlm.nih.gov/pubmed/1666063.
  63. Thomson EC, Nastouli E, Main J, et al. Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV. AIDS. 2009;23(1):89-93. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19050390.
  64. Sulkowski MS, Thomas DL. Hepatitis C in the HIV-infected person. Ann Intern Med. 2003;138(3):197-207. Available at: https://pubmed.ncbi.nlm.nih.gov/12558359.
  65. Feld JJ. Hepatitis C virus diagnostics: the road to simplification. Clin Liver Dis (Hoboken). 2018;12(5):125-129. Available at: https://pubmed.ncbi.nlm.nih.gov/30988927.
  66. Taylor JL, Johnson S, Cruz R, Gray JR, Schiff D, Bagley SM. Integrating harm reduction into outpatient opioid use disorder treatment settings: harm reduction in outpatient addiction treatment. J Gen Intern Med. 2021;36(12):3810-3819. Available at: https://pubmed.ncbi.nlm.nih.gov/34159545.
  67. Platt L, Minozzi S, Reed J, et al. Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs. Cochrane Database Syst Rev. 2017;9(9):Cd012021. Available at: https://pubmed.ncbi.nlm.nih.gov/28922449.
  68. Schulte B, Schmidt CS, Strada L, et al. Hepatitis C virus prevalence and incidence in a large nationwide sample of patients in opioid substitution treatment in Germany: a prospective cohort study. Clin Infect Dis. 2020;70(10):2199-2205. Available at: https://pubmed.ncbi.nlm.nih.gov/31631215.
  69. Jin F, Dore GJ, Matthews G, et al. Prevalence and incidence of hepatitis C virus infection in men who have sex with men: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(1):39-56. Available at: https://pubmed.ncbi.nlm.nih.gov/33217341.
  70. Vanhommerig JW, Lambers FA, Schinkel J, et al. Risk factors for sexual transmission of hepatitis C virus among human immunodeficiency virus-infected men who have sex with men: a case-control study. Open Forum Infect Dis. 2015;2(3):ofv115. Available at: https://pubmed.ncbi.nlm.nih.gov/26634219.
  71. Hampel B, Kusejko K, Kouyos RD, et al. Chemsex drugs on the rise: a longitudinal analysis of the Swiss HIV Cohort Study from 2007 to 2017. HIV Med. 2020;21(4):228-239. Available at: https://pubmed.ncbi.nlm.nih.gov/31849182.
  72. Naggie S, Holland DP, Sulkowski MS, Thomas DL. Hepatitis C virus postexposure prophylaxis in the healthcare worker: why direct-acting antivirals don't change a thing. Clin Infect Dis. 2017;64(1):92-99. Available at: https://pubmed.ncbi.nlm.nih.gov/27682067.
  73. Page K, Melia MT, Veenhuis RT, et al. Randomized trial of a vaccine regimen to prevent chronic HCV infection. N Engl J Med. 2021;384(6):541-549. Available at: https://pubmed.ncbi.nlm.nih.gov/33567193.
  74. Lambers FA, Brinkman K, Schinkel J, et al. Treatment of acute hepatitis C virus infection in HIV-infected MSM: the effect of treatment duration. AIDS. 2011;25(10):1333-1336. Available at: https://pubmed.ncbi.nlm.nih.gov/21516025.
  75. Piroth L, Larsen C, Binquet C, et al. Treatment of acute hepatitis C in human immunodeficiency virus-infected patients: the HEPAIG study. Hepatology. 2010;52(6):1915-1921. Available at: https://pubmed.ncbi.nlm.nih.gov/21064156.
  76. Martin NK, Thornton A, Hickman M, et al. Can hepatitis C virus (HCV) direct-acting antiviral treatment as prevention reverse the HCV epidemic among men who have sex with men in the United Kingdom? Epidemiological and modeling insights. Clin Infect Dis. 2016;62(9):1072-1080. Available at: https://pubmed.ncbi.nlm.nih.gov/26908813.
  77. Vento S. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. J Viral Hepat. 2000;7 Suppl 1:7-8. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10866837.
  78. Wiley TE, McCarthy M, Breidi L, McCarthy M, Layden TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology. 1998;28(3):805-809. Available at: https://pubmed.ncbi.nlm.nih.gov/9731576.
  79. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723-750. Available at: https://pubmed.ncbi.nlm.nih.gov/29624699.
  80. Merchante N, Giron-Gonzalez JA, Gonzalez-Serrano M, et al. Survival and prognostic factors of HIV-infected patients with HCV-related end-stage liver disease. AIDS. 2006;20(1):49-57. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16327319.
  81. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351(5):438-450. Available at: https://pubmed.ncbi.nlm.nih.gov/15282351.
  82. Chung RT, Andersen J, Volberding P, et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351(5):451-459. Available at: https://pubmed.ncbi.nlm.nih.gov/15282352.
  83. Solomon SS, Wagner-Cardoso S, Smeaton L, et al. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol. 2022. Available at: https://pubmed.ncbi.nlm.nih.gov/35026142.
  84. Dore GJ, Feld JJ, Thompson A, et al. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol. 2020;72(3):431-440. Available at: https://pubmed.ncbi.nlm.nih.gov/31655134.
  85. Butt AA, Yan P, Shaikh OS, Chung RT, Sherman KE. Treatment adherence and virological response rates in hepatitis C virus infected persons treated with sofosbuvir-based regimens: results from ERCHIVES. Liver Int. 2016;36(9):1275-1283. Available at: https://pubmed.ncbi.nlm.nih.gov/26928927.
  86. Ward KM, Falade-Nwulia O, Moon J, et al. Non-adherence to LDV/SOF did not predict SVR in a randomized controlled trial of HIV/HCV coinfected persons who use drugs. J Infect Dis. 2021. Available at: https://pubmed.ncbi.nlm.nih.gov/34543417.
  87. Cunningham EB, Hajarizadeh B, Amin J, et al. Adherence to once-daily and twice-daily direct-acting antiviral therapy for hepatitis C infection among people with recent injection drug use or current opioid agonist therapy. Clin Infect Dis. 2020;71(7):e115-e124. Available at: https://pubmed.ncbi.nlm.nih.gov/31677262.
  88. Schmid P, Bregenzer A, Huber M, et al. Progression of liver fibrosis in HIV/HCV co-infection: a comparison between non-invasive assessment methods and liver biopsy. PLoS One. 2015;10(9):e0138838. Available at: https://pubmed.ncbi.nlm.nih.gov/26418061.
  89. Chou R, Wasson N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection. Ann Intern Med. 2013;159(5):372. Available at: https://pubmed.ncbi.nlm.nih.gov/24026329.
  90. Bhattacharya D, Belperio PS, Shahoumian TA, et al. Effectiveness of all-oral antiviral regimens in 996 human immunodeficiency virus/hepatitis C virus genotype 1-coinfected patients treated in routine practice. Clin Infect Dis. 2017;64(12):1711-1720. Available at: https://pubmed.ncbi.nlm.nih.gov/28199525.
  91. Kim HN, Nance RM, Williams-Nguyen JS, et al. Effectiveness of direct-acting antiviral therapy in patients with human immunodeficiency virus-hepatitis C virus coinfection in routine clinical care: a multicenter study. Open Forum Infect Dis. 2019;6(4):ofz100. Available at: https://pubmed.ncbi.nlm.nih.gov/30949539.
  92. Amele S, Peters L, Rodger A, et al. Effectiveness and safety of interferon-free direct-acting antiviral hepatitis C virus therapy in HIV/hepatitis C virus coinfected individuals: results from a pan-European study. J Acquir Immune Defic Syndr. 2021;86(2):248-257. Available at: https://pubmed.ncbi.nlm.nih.gov/33079903.
  93. Panel on Antiretroviral Guidelines for Adults and Adolescents. Hepatitis C virus/HIV coinfection. 2022. Available at: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/hepatitis-c-virus-hiv-coinfection?view=full.
  94. Kosloski MP, Oberoi R, Wang S, et al. Drug-drug interactions of glecaprevir and pibrentasvir coadministered with human immunodeficiency virus antiretrovirals. J Infect Dis. 2020;221(2):223-231. Available at: https://pubmed.ncbi.nlm.nih.gov/31504702.
  95. Mogalian E, Stamm LM, Osinusi A, et al. Drug-drug interaction studies between hepatitis C virus antivirals sofosbuvir/velpatasvir and boosted and unboosted human immunodeficiency virus antiretroviral regimens in healthy volunteers. Clin Infect Dis. 2018;67(6):934-940. Available at: https://pubmed.ncbi.nlm.nih.gov/29522076.
  96. Rockstroh JK, Lacombe K, Viani RM, et al. Efficacy and safety of glecaprevir/pibrentasvir in patients coinfected with hepatitis C virus and human immunodeficiency virus type 1: the EXPEDITION-2 study. Clin Infect Dis. 2018;67(7):1010-1017. Available at: https://pubmed.ncbi.nlm.nih.gov/29566246.
  97. Wyles D, Bräu N, Kottilil S, et al. Sofosbuvir and velpatasvir for the treatment of hepatitis C virus in patients coinfected with human immunodeficiency virus type 1: an open-label, Phase 3 study. Clin Infect Dis. 2017;65(1):6-12. Available at: https://pubmed.ncbi.nlm.nih.gov/28369210.
  98. Brown RS, Jr., Buti M, Rodrigues L, et al. Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: the EXPEDITION-8 trial. J Hepatol. 2020;72(3):441-449. Available at: https://pubmed.ncbi.nlm.nih.gov/31682879.
  99. Cornberg M, Jimenez AMA, Aghemo A, et al. Safety and effectiveness using 8 weeks of glecaprevir/pibrentasvir in HCV-infected treatment-naive patients with compensated cirrhosis: the CREST study. Hepatology. 2021;74:575A-576A. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239949.
  100. Popping S, Hullegie SJ, Boerekamps A, et al. Early treatment of acute hepatitis C infection is cost-effective in HIV-infected men-who-have-sex-with-men. PLoS One. 2019;14(1):e0210179. Available at: https://pubmed.ncbi.nlm.nih.gov/30629662.
  101. Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376(22):2134-2146. Available at: https://pubmed.ncbi.nlm.nih.gov/28564569.
  102. Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 2017;66(2):389-397. Available at: https://pubmed.ncbi.nlm.nih.gov/28128852.
  103. Wyles D, Weiland O, Yao B, et al. Retreatment of patients who failed glecaprevir/pibrentasvir treatment for hepatitis C virus infection. J Hepatol. 2019;70(5):1019-1023. Available at: https://pubmed.ncbi.nlm.nih.gov/30857780.
  104. Lok AS, Sulkowski MS, Kort JJ, et al. Efficacy of glecaprevir and pibrentasvir in patients with genotype 1 hepatitis C virus infection with treatment failure after NS5A inhibitor plus sofosbuvir therapy. Gastroenterology. 2019;157(6):1506-1517.e1501. Available at: https://pubmed.ncbi.nlm.nih.gov/31401140.
  105. Belperio PS, Shahoumian TA, Loomis TP, Backus LI. Real-world effectiveness of sofosbuvir/velpatasvir/voxilaprevir in 573 direct-acting antiviral experienced hepatitis C patients. J Viral Hepat. 2019;26(8):980-990. Available at: https://pubmed.ncbi.nlm.nih.gov/31012179.
  106. Llaneras J, Riveiro-Barciela M, Lens S, et al. Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs. J Hepatol. 2019;71(4):666-672. Available at: https://pubmed.ncbi.nlm.nih.gov/31203153.
  107. Degasperi E, Spinetti A, Lombardi A, et al. Real-life effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients with previous DAA failure. J Hepatol. 2019;71(6):1106-1115. Available at: https://pubmed.ncbi.nlm.nih.gov/31433303.
  108. Papaluca T, Roberts SK, Strasser SI, et al. Efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir for hepatitis C virus (HCV) NS5A-inhibitor experienced patients with difficult to cure characteristics. Clin Infect Dis. 2021;73(9):e3288-e3295. Available at: https://pubmed.ncbi.nlm.nih.gov/32887983.
  109. The American College of Obstetricians and Gynecologists. Viral hepatitis in pregnancy. 2022. Available at: https://www.acog.org/en/clinical/clinical-guidance/practice-bulletin/articles/2007/10/viral-hepatitis-in-pregnancy.
  110. Prasad M. Risk factors for mother to child transmission of hepatitis C (HCV): a prospective observational study. American Journal of Obstetrics & Gynecology. 2022;226(S5). Available at: https://www.ajog.org/article/S0002-9378(21)01238-2/fulltext.
  111. Rossi RM, Wolfe C, Brokamp R, et al. Reported prevalence of maternal hepatitis C virus infection in the United States. Obstet Gynecol. 2020;135(2):387-395. Available at: https://pubmed.ncbi.nlm.nih.gov/31923064.
  112. Patrick SW, Bauer AM, Warren MD, Jones TF, Wester C. Hepatitis C virus infection among women giving birth - Tennessee and United States, 2009–2014. MMWR Morb Mortal Wkly Rep. 2017;66(18):470-473. Available at: https://pubmed.ncbi.nlm.nih.gov/28493860.
  113. The American College of Obstetricians and Gynecologists. Routine hepatitis C virus screening in pregnant individuals. 2021. Available at: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/05/routine-hepatitis-c-virus-screening-in-pregnant-individuals.
  114. Jhaveri R, Broder T, Bhattacharya D, Peters MG, Kim AY, Jonas MM. Universal screening of pregnant women for hepatitis C: the time is now. Clin Infect Dis. 2018;67(10):1493-1497. Available at: https://pubmed.ncbi.nlm.nih.gov/30215670.
  115. Chaillon A, Rand EB, Reau N, Martin NK. Cost-effectiveness of universal hepatitis C virus screening of pregnant women in the United States. Clin Infect Dis. 2019;69(11):1888-1895. Available at: https://pubmed.ncbi.nlm.nih.gov/30689769.
  116. McMenamin MB, Jackson AD, Lambert J, et al. Obstetric management of hepatitis C-positive mothers: analysis of vertical transmission in 559 mother-infant pairs. Am J Obstet Gynecol. 2008;199(3):315.e311-315. Available at: https://pubmed.ncbi.nlm.nih.gov/18771997.
  117. Ghamar Chehreh ME, Tabatabaei SV, Khazanehdari S, Alavian SM. Effect of cesarean section on the risk of perinatal transmission of hepatitis C virus from HCV-RNA+/HIV- mothers: a meta-analysis. Arch Gynecol Obstet. 2011;283(2):255-260. Available at: https://pubmed.ncbi.nlm.nih.gov/20652289.
  118. Mariné-Barjoan E, Berrébi A, Giordanengo V, et al. HCV/HIV co-infection, HCV viral load and mode of delivery: risk factors for mother-to-child transmission of hepatitis C virus? AIDS. 2007;21(13):1811-1815. Available at: https://pubmed.ncbi.nlm.nih.gov/17690581.
  119. European Paediatric Hepatitis C Virus Network. A significant sex--but not elective cesarean section--effect on mother-to-child transmission of hepatitis C virus infection. J Infect Dis. 2005;192(11):1872-1879. Available at: https://pubmed.ncbi.nlm.nih.gov/16267757.
  120. Read JS, Tuomala R, Kpamegan E, et al. Mode of delivery and postpartum morbidity among HIV-infected women: the women and infants transmission study. J Acquir Immune Defic Syndr. 2001;26(3):236-245. Available at: https://pubmed.ncbi.nlm.nih.gov/11242196.
  121. Grubert TA, Reindell D, Kästner R, et al. Rates of postoperative complications among human immunodeficiency virus-infected women who have undergone obstetric and gynecologic surgical procedures. Clin Infect Dis. 2002;34(6):822-830. Available at: https://pubmed.ncbi.nlm.nih.gov/11850864.
  122. Grubert TA, Reindell D, Kästner R, Lutz-Friedrich R, Belohradsky BH, Dathe O. Complications after caesarean section in HIV-1-infected women not taking antiretroviral treatment. Lancet. 1999;354(9190):1612-1613. Available at: https://pubmed.ncbi.nlm.nih.gov/10560681.
  123. Fiore S, Newell ML, Thorne C. Higher rates of post-partum complications in HIV-infected than in uninfected women irrespective of mode of delivery. AIDS. 2004;18(6):933-938. Available at: https://pubmed.ncbi.nlm.nih.gov/15060441.
  124. D'Ambrosio R, Pasulo L, Puoti M, et al. Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C. J Hepatol. 2019;70(3):379-387. Available at: https://pubmed.ncbi.nlm.nih.gov/30472321.
  125. Mangia A, Milligan S, Khalili M, et al. Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5,552 patients from 12 cohorts. Liver Int. 2020;40(8):1841-1852. Available at: https://pubmed.ncbi.nlm.nih.gov/32449966.
  126. Chappell CA, Scarsi KK, Kirby BJ, et al. Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study. Lancet Microbe. 2020;1(5):e200-e208. Available at: https://pubmed.ncbi.nlm.nih.gov/32939459.
  127. Hegenbarth K, Maurer U, Kroisel PM, Fickert P, Trauner M, Stauber RE. No evidence for mutagenic effects of ribavirin: report of two normal pregnancies. Am J Gastroenterol. 2001;96(7):2286-2287. Available at: https://pubmed.ncbi.nlm.nih.gov/11467687.

Treating HCV Infection

Simplified Approach to HCV Treatment

Box 1. Characteristics of People with HIV for Whom Simplified Hepatitis C Virus Treatment Is Not Recommendeda
  1. Prior HCV treatment (Reinfection after prior successful therapy is not an exclusion.)
  2. Decompensated cirrhosisb
  3. TDF-containing regimen with an eGFR <60mL/min
  4. On efavirenz, etravirine, nevirapine, or boosted HIV-1 protease inhibitorsc
  5. Untreated chronic HBV infection
  6. Pregnancy
a People with HIV and HCV infection who meet these exclusion criteria should be treated for HCV following standard approaches (see the AASLD/IDSA HCV Guidance).

b Including, but not limited to, current or prior variceal bleeding, ascites, or hepatic encephalopathy

c People with HIV on boosted protease inhibitors are not eligible for treatment with glecaprevir/pibrentasvir and may require on-treatment monitoring.
Key: eGFR = estimated glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; TDF = tenofovir disoproxil fumarate


Box 2. Pre-treatment Assessment Under Simplified Approach
  1. Creatinine, liver function tests, and complete blood count
  2. HCV RNA
  3. Hepatitis B surface antigen
  4. Initial fibrosis staging with FIB-4 (FIB-4 calculator)a
  5. Medication and drug interaction review
  6. HCV genotype required if cirrhosis is present
a Additional testing may be required if results are indeterminate (see text).

Key: HCV = hepatitis C virus

Drug–Drug Interactions

Summary of Major Drug Interactions Between HIV and HCV Antivirals
HIV AntiviralsGlecaprevir/PibrentasvirSofosbuvir/Velpatasvir
EFV, ETR, NVP, and other strong CYP 3A4 and P-gp inducersSignificant decrease in glecaprevir and pibrentasvir concentrations
Significant decrease in velpatasvir concentrations
PI/r, PI/c, unboosted ATVSignificant increase in glecaprevir and pibrentasvir concentrations

Boosted PIs may increase velpatasvir concentrations, but no significant adverse events in clinical trial

Coadministration allowed

TDF, TAFCoadministration allowed

TAF preferred

If TDF is used with boosted PIs if GFR <60 mL/min, monitoring is recommended.

RPV, DOR, EVG/c, RAL, BIC, DTG, ABC, FTC, 3TC, MVCCoadministration allowedCoadministration allowed
Key: 3TC = lamivudine; ABC = abacavir; ATV = atazanavir; BIC = bictegravir; CYP = cytochrome P450; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG/c = elvitegravir/cobicistat; GFR = glomerular filtration rate; FTC = emtricitabine; MVC = maraviroc; NVP = nevirapine; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; P-gp = p-glycoprotein; RAL = raltegravir; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

Special Considerations During Pregnancy

Download Guidelines