Although the World Health Organization (WHO) has set a goal to significantly reduce hepatitis C virus (HCV)-related morbidity and mortality rates by 2030, HCV continues to pose a major public health threat.1 In 2016, an estimated 18,000 deaths were attributed to HCV infection.2 The demographics of this disease, however, including who is being infected and the mode of infection, have shifted. Before the 1990s, HCV infection was commonly found in older adults who became infected following blood transfusions or organ transplantations.3,4 Once testing for the HCV antibody in the blood became routine in the early 1990s, there was a sharp decline in incident HCV cases until 2005, when the next wave of HCV transmission began as a result of the opioid epidemic and, subsequently, an increase in illicit drug use.3,4 Today, injection drug use is the greatest risk factor for HCV infection, and some data suggest that people who use cocaine may be at particularly high risk compared with other drug users.5 However, this increased risk appears to extend to those who do not inject drugs, which has led to initiatives to better understand the association between cocaine use and HCV transmission and clearance and strategies for prevention.

Injection Cocaine Use and HCV Risk

Syringe sharing among illicit injection drug users is the most documented route of HCV infection, but those who inject cocaine may be at particularly high risk.5 A retrospective study assessing data from 5 inpatient studies conducted at the New York State Psychiatric Institute in New York City that included 120 volunteers who were categorized as heroin-dependent, found 42 of them (35%) to be HCV-positive, with those reporting cocaine injection during the previous month as having a 9-fold higher risk of being HCV-positive compared with those who did not use cocaine or who had consumed it via another method.6 In contrast, those who reported injecting heroin had a 3.5-fold increased risk for HCV infection compared with intranasal heroin users.6

Several findings reported in the literature may help explain why the risk of HCV infection is particularly high among injection cocaine users vs those who inject other drugs. An assessment of first-time drug injection practices among homeless youth in Montreal, Canada, reported that those who injected illicit drugs tended to use a clean needle at first injection,7 and further, those who injected heroin tended to do so under less risky circumstances than those who injected cocaine, such as by having a close friend or sexual partner perform the injection rather than another person.8 This finding was supported by another study that found cocaine users to have riskier social networks than heroin users, including a larger network of other injection drug users and a greater likelihood of living in an unstable housing situation.9 In a study comparing demographic characteristics among individuals who use heroin, methamphetamine, or cocaine, >90% of those who reported cocaine as the first drug they used were homeless at the time the study was conducted, demonstrating the increased vulnerability of this population.8

Another factor that has been hypothesized to increase the risk for HCV transmission among cocaine injectors is the use of crack cocaine vs powdered cocaine.10 While powdered cocaine is water soluble, crack cocaine requires the addition of an acid such as lemon juice or vinegar to make it soluble for injection.10 This addition can damage veins, which may increase the risk of transmitting bloodborne pathogens, including HCV; however, studies are needed to confirm this hypothesis.8,10

Noninjection Cocaine Use and HCV Risk

While HCV transmission risk has consistently been assessed as higher with the use of injectable vs noninjectable forms of cocaine, noninjecting drug users are still at greater risk of acquiring HCV compared with the general population.11 In a Brazilian study, HCV prevalence among noninjecting drug users ranged from 3.6% to 12.6%, depending on their risk factors, with the highest risk occurring among those who reported sharing snorting implements and/or having sex with a partner who tested positive for HCV or HIV.12 The increased risk for HCV transmission among noninjection cocaine users is likely multifactorial, including risky drug use practices, such as sharing drug paraphernalia (eg, pipes, straws), and a greater propensity for engaging in other risky behaviors, such as multiple sexual partners, not using condoms, and tattooing or piercings performed by nonprofessionals who may use unsanitary tools.5

HCV RNA has been detected on drug paraphernalia and in bodily fluids that come in contact with drug paraphernalia.5,13 In a small Canadian study that tested pipes used for crack cocaine for HCV RNA shortly after use by 51 individuals from the inner city who use crack cocaine, HCV was detected on 1 of the 22 pipes (2%) whose owners tested positive for HCV.13 The pipe’s owner was found to have multiple oral sores, and the study investigators suggested that the presence of sores and the condition of drug paraphernalia may affect HCV transmission risk among oral crack users.13

Intranasal transmission of HCV has also been demonstrated to be plausible.14 An assessment of nasal secretion samples from a cohort of low income, intranasal drug users in New York City with chronic, active HCV infection (n = 38) found a high prevalence of blood (74%), with 13% of samples also testing positive for HCV RNA.14 Furthermore, during simulated intranasal drug use, blood and HCV RNA were transferred onto 8% and 5% of sniffing implements, respectively.14 Based on these findings, the investigators concluded that the study established the validity of 2 primary virologic preconditions for intranasal HCV transmission: presence of blood and HCV RNA in the nasal secretions of HCV-positive people, and the ability of blood and HCV RNA to be transferred from the nasal mucosa onto sniffing implements.14 However, the investigators noted that the transmission window and amount of virus needed for transmission have yet to be determined.

While sexual intercourse is not a major risk factor for HCV transmission, risk is increased when there is exposure to infected blood, which can occur if a sexual encounter occurs during menses, there are oral or genital lesions from a sexually transmitted infection (STI), or the sexual encounter leads to lacerations. Studies have shown that people who use cocaine often engage in sexual behaviors that increase their risk for HCV infection. A 2017 study reported cocaine use to be associated with a dose-related increase in sexual desire and a lower likelihood of condom use when safer sex necessitated a delay, such as a condom not being readily available, or when the risk of acquiring a STI was not thought to be a certainty.15 Additionally, because crack cocaine users tend to be of lower socioeconomic status, there may be a greater propensity to exchange sex for drugs.16 A study of 206 street-based female sex workers who smoked crack cocaine found that 49% reported sex-for-crack exchanges over the 18-month study period.16 In another study that examined 2042 drug-using women in 23 cities who reported having exchanged sex for drugs and/or money in the 30 days preceding the study, those who exchanged sex only for drugs (n = 117) or for both drugs and money (n = 965) were more likely to use alcohol, smoke crack cocaine, have unprotected sex, and to have sex with a drug injector than those who exchanged sex only for money (n = 960).17

Drug Use Setting, Cocaine, and HCV Risk

Recent research using brain scans suggests heroin stimulates a more pleasurable response when taken at home, whereas cocaine is more pleasurable when taken outside of the home, such as in a club, bar, or at a party.18 This is because heroin induces a sedative state, whereas cocaine is a stimulant, thus making these respective locations more pleasurable for the emotional state produced. Although the study did not evaluate the implications of this finding on the risk for STI transmission, it may provide another explanation for why HCV infection is particularly prevalent among cocaine users. A greater likelihood of being outside of the home while experiencing the effects of cocaine may increase the potential for risky behaviors, including those that are violent in nature, and increase exposure to individuals who have HCV and/or other STIs.

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Cocaine, the Immune System, and HCV Clearance

Approximately 15% to 45% of persons infected with HCV eliminate the virus on their own without the need for treatment, while the remaining 55% to 85% progress to chronic HCV infection.11 Persons who use cocaine may be more susceptible to viral infections and have greater difficulty clearing them spontaneously compared with the general population, as cocaine can impair the immune system.5 Cocaine use has been associated with a significant decrease in mitogen-induced lymphocyte proliferation, decreased cytokine formation, impairment of dendritic cells, loss of T-cell stimulation, and impaired antibody formation.5 However, studies are needed to clarify how HCV and cocaine may work together to prevent HCV from being cleared by the body.

Moderate-to-high alcohol use, which is common among cocaine users, may further impair the immune system, increasing the likelihood of viral and other infections.19,20 Alcohol is known to alter the gut microbiome, as well as damage epithelial cells, T cells, and neutrophils in the gastrointestinal system, thus affecting the maturation and function of the immune system.20 These changes enable bacterial products to breach the gut and migrate into the circulation where they can trigger the immune system and cause inflammation in the liver, increasing the risk for hepatic cirrhosis and hepatocellular carcinoma.19 This can be particularly devastating for patients with chronic HCV infection because they are already at high risk for cirrhosis and hepatocellular carcinoma.

Prevention Strategies

No vaccine is yet available to prevent chronic HCV infection, and in October 2019 a setback was reported when the results of the first HCV vaccine efficacy trial failed to show benefit in preventing chronic HCV infections.21 Subsequently, preventive strategies will need to continue focusing on risk-mitigation strategies in at-risk groups for some time, including high-risk groups like cocaine users.5 Such efforts may include strategies to reduce sharing of drug paraphernalia, including needles, pipes, and straws, whether through educational programs, distribution of new and sterile needles and other paraphernalia, and/or promotion of drug-cessation programs.5 To ensure the greatest benefit, public health interventions for cocaine users will need to be tailored to each individual person and address the overlapping epidemics observed in this population, including HCV infection, alcohol use, and the use of other illicit substances.19

Addressing mental health is another important aspect of prevention and risk mitigation.5 A study conducted in Madrid, Spain that included 837 outpatients, 488 of whom had a lifetime diagnosis of cocaine abuse or dependence and 222 who did not, found a high prevalence of mental disorders in those addicted to cocaine, including mood and anxiety disorders (73.4%), personality disorders (49.6%), and a variety of other diagnoses, such as antisocial personality disorder, agoraphobia, and post-traumatic stress disorder.22 These conditions in the setting of HCV may increase the risk for depression and suicidality, affect the ability to successfully complete drug addiction programs, and increase the propensity to engage in risky behaviors that can also increase the likelihood of HCV transmission to others.5

Cocaine users who are found to have HCV infection should be offered HCV treatment.5 Many illicit drug users with HCV infection can achieve sustained virologic response, even in the setting of psychiatric comorbidities or continued illicit drug use while receiving HCV treatment.23 However, to optimize outcomes, HCV treatment should be undertaken using a multidisciplinary approach, which may include an HCV expert, substance abuse expert, mental health provider, and social services, as well as access to support groups and healthcare providers who can help coordinate care, provide education, and manage adverse effects and any comorbidities.23


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