Hepatitis C and HIV in people who use drugs

A woman in her thirties comes to the health unit with an abscess on her forearm. She has been injecting drugs for a few years and has been on methadone for six months. The dressing is done, the antibiotic is prescribed and the visit ends. No one offers a hepatitis C or HIV test. When someone thinks of it, weeks later, the sentence that appears in the chart is "treat when abstinent". The scene is fictional and was written for teaching. This text uses that encounter as a setting for clinical reasoning: how to think through the cascade of care for hepatitis C and HIV in people who use drugs, from testing to treatment, and which biases make the professional postpone decisions that the evidence supports.

NEXO is a daily medical diagnosis game: one clinical case a day, up to six progressive clues, and ICD-10 proximity feedback across five levels.

The post on harm reduction beyond all or nothing already discusses prevention, with syringe exchange and agonist treatment; here the focus is the next step: diagnosis, the decision to treat, adherence and reinfection. The text avoids being a protocol. Regimens, tests and workflows follow the guidelines and protocols of each service. If you play the case of the day on NEXO, you will recognize the move: the clue you fail to look for is the one that changes the diagnosis.

Key points

• Every contact with a person who uses drugs is an opportunity to offer a hepatitis C and HIV test.
• Clinical trials showed high hepatitis C cure rates with direct-acting antivirals in people with recent injection drug use and on agonist treatment, regardless of use during treatment.
• Reinfection after cure happens, is lower than the primary infection rate and should be treated as clinical data, not as failure or a reason to deny treatment.
• Immediate start of antiretroviral therapy brings net benefit, and rapid start, including same-day, improves viral suppression and retention in care.
• Pre-exposure prophylaxis reduced HIV infection in people who inject drugs in a randomized trial.

Why the cascade of care breaks down

The cascade of care describes the steps a person goes through between having an infection and being cured or having the virus suppressed: being tested, receiving the diagnosis, being linked to care, starting treatment, staying on treatment and being followed up afterward. In people who use drugs, every step has losses. Part of these losses comes from structural barriers, such as rigid schedules and the requirement of several visits. Another part comes from clinical decisions postponed by beliefs that the evidence has already revised.

The AASLD and IDSA guideline on hepatitis C, in its 2023 update, recommends universal testing and simplified treatment, and recognizes incomplete adherence as something that can be managed within treatment (Bhattacharya and colleagues, 2023). The World Health Organization published updated recommendations in 2022 to simplify the delivery of services and the diagnosis of hepatitis C, with a focus on decentralizing and integrating care (WHO, 2022).

Where the person is lost

Step	What usually blocks it	Reasoning question	What helps
Offering the test	The test is forgotten in visits for another reason	Can this contact include the test?	Offer the test at every contact
Confirmation of the diagnosis	Multiple returns to confirm the result	Can the confirmatory test be collected now?	Same-day collection, when the service allows it
Linkage	Referral to another distant service	Who can treat here?	Treatment at the service the person already attends
Starting treatment	Requirement of abstinence or of too many tests	Does any criterion justify waiting?	Simplified regimens from the guidelines
Adherence	Missed doses seen as failure	What makes daily taking easier?	Pair taking with the routine and the agonist
Follow-up	No test after cure	When to test again?	Periodic testing if there is exposure

The table is a support for reasoning, not a mandatory workflow. The details of each step follow the service protocol.

Testing at every contact

The opening scene shows the most common moment of loss: the person is at the service, but the test is left for later. An abscess, an agonist renewal appointment or an emergency department visit are opportunities. Hepatitis C testing usually starts with antibody testing and continues with viral RNA testing to confirm active infection, and collecting both steps at the same time reduces losses (Schillie et al., 2020). For HIV, rapid tests allow a result at the same appointment.

How to offer the test

• Offer the test as part of the routine, to everyone, and not as suspicion about someone.
• Explain what the test shows and what happens if the result is positive.
• Agree on how the person will receive the result and through which channel.
• Use the same collection for other indicated tests, such as hepatitis B.
• Record the date of the last test to guide the next one.

The way the test is offered changes the response. Kelly and Westerhoff showed that the way a person who uses substances is named changes professionals' judgment about blame and punishment (Kelly and Westerhoff, 2010). When the test is presented as routine, the conversation is lighter. The post about stigma and language shows how the label changes conduct.

Communicating the result

The moment of delivering the result is an opportunity to build a connection. A positive hepatitis C result can be presented together with the news that there is a short treatment with a high cure rate, and that drug use is compatible with it. A positive HIV result calls for time, listening and a clear path to starting antiretroviral therapy. A negative result opens the conversation about prevention, PrEP and when to test again. In all cases, agreeing on the next step before the person leaves the service reduces the chance of being lost between the result and treatment.

Treating hepatitis C without requiring abstinence

For many years, abstinence was treated as a prerequisite for hepatitis C treatment. The old regimens, with interferon, had significant adverse effects and a long duration, and the requirement seemed reasonable. With direct-acting antivirals, the evidence changed.

The SIMPLIFY trial treated people with recent injection drug use with sofosbuvir and velpatasvir and found high rates of sustained virological response. The authors concluded that treatment should be offered to people who inject drugs regardless of current use, and that recent injection drug use is no longer a reason to deny treatment (Grebely et al., 2018). The C-EDGE CO-STAR trial, randomized and with people on agonist treatment, showed high cure rates with elbasvir and grazoprevir, with no effect of drug use at the start of or during treatment on response or adherence (Dore et al., 2016).

Before starting: what to check

Assessment before treatment is usually simpler than one might imagine, and the simplified guidelines were written precisely to reduce steps (Bhattacharya et al., 2023). Broadly, the reasoning goes through four questions. Are there signs of cirrhosis that change the regimen or follow-up? Is there hepatitis B or HIV coinfection? Are there medications in use with a relevant interaction with the chosen antiviral? Is the person pregnant or could they become pregnant during treatment? Once these questions are answered, most people can start treatment at the service they already attend, without referral to a specialist, according to the local organization.

What changes in the reasoning

The question is no longer "does this person deserve treatment?" and becomes "what do I need to organize so that treatment works?". This includes assessing liver fibrosis, checking drug interactions, testing for hepatitis B and HIV coinfection and agreeing on the logistics of doses. The choice of regimen follows the guidelines and the service protocol.

In the opening scene, the woman has been on methadone treatment for six months and attends the service regularly. This connection is an advantage: hepatitis C treatment can be integrated into the agonist routine. The post about buprenorphine or methadone discusses how the choice of agonist fits into the person's life, and the same logic applies to antiviral treatment.

Adherence: a missed dose is information

Incomplete adherence is common in any long-term treatment, and hepatitis C treatment lasts weeks. The AASLD and IDSA guideline acknowledges that incomplete adherence happens and gives guidance on how to manage it (Bhattacharya et al., 2023). In C-EDGE CO-STAR, drug use during treatment did not affect adherence or cure (Dore et al., 2016).

A missed dose is information about the person's routine, not a sign that they "don't want treatment". The useful question is what happened that day and what would make the next dose easier to take.

Strategies that often help

1. Pair taking the antiviral with a daily habit, such as the agonist dose.
2. Offer to supply the tablets at the service itself, when possible.
3. Use pill organizers or phone reminders, according to the person's preference.
4. Agree on what to do if a dose is missed, so the person does not abandon treatment.
5. Keep in touch between appointments, by message or through peers, when the service has that structure.

Motivational interviewing helps when there is ambivalence: the person wants to be cured and fears the treatment routine or the adverse effects. The post on motivational interviewing for students and residents explains how to explore both sides without pressure.

Reinfection: a clinical finding, not a failure

Reinfection after cure is one of the concerns that most often make professionals postpone treatment. The evidence helps put the question back in perspective. A meta-analysis by Hajarizadeh et al. showed that reinfection after successful treatment in people who inject drugs does happen, but at a lower rate than primary infection in this population, and concluded that it should not be used as a reason to deny treatment. Reinfection was lower in people on agonist treatment and without recent injecting drug use, and the authors recommend harm reduction measures and testing after treatment (Hajarizadeh et al., 2020).

An analysis of people who inject drugs treated with direct-acting antivirals linked reinfection to younger age and to sharing needles and syringes (Cunningham et al., 2021). These findings guide follow-up: those who remain exposed need periodic testing and access to prevention measures.

What to do when it happens

Reinfection calls for the same reasoning as the first infection: confirm the diagnosis, offer new treatment according to the guideline and review prevention measures with the person. Treating reinfection as a personal failure pushes the person away from the service and reduces the chance of cure. Treating it as a clinical finding keeps the connection and opens space to talk about harm reduction.

Testing after cure

Cure of hepatitis C does not leave immunity. Cure is confirmed by undetectable viral RNA 12 weeks or more after the end of treatment, the so-called sustained virological response (AASLD-IDSA, 2023). Antibodies remain positive after treatment, and so follow-up of those who remain exposed uses viral RNA testing, not antibody testing, to detect a new infection. The frequency of tests after cure follows the guideline and each person's risk of exposure. Arranging this testing at the time of discharge from treatment, rather than leaving it for a future appointment, increases the chance that it happens. Explaining the reason also helps: the person understands that testing again is part of care, not distrust.

HIV: testing, rapid start and PrEP

The same cascade logic applies to HIV. Testing is offered at every contact, and a positive result leads to a discussion about starting antiretroviral therapy. The START trial showed that starting antiretroviral therapy in adults with a CD4 count above 500 cells per cubic millimeter brought a net benefit compared with delaying the start until the count fell (INSIGHT START Study Group, 2015). A systematic review showed that accelerated start, including same-day start, increased viral suppression and retention in care, and supported the WHO recommendation for rapid start (Ford et al., 2018).

For people with a negative result who remain exposed, pre-exposure prophylaxis enters the conversation. The Bangkok Tenofovir Study, a randomized trial with people who inject drugs, showed that daily oral tenofovir reduced HIV infection compared with placebo (Choopanya et al., 2013).

PrEP is also an entry point: those who return periodically to renew prophylaxis get regular HIV tests and can, in the same visit, repeat the hepatitis C test, talk about treatment for substance use and receive prevention supplies. Each renewal becomes a new contact with the care cascade.

Points to watch in the reasoning

• Interactions between antiretrovirals, hepatitis C antivirals and opioid agonists, checked with the clinical pharmacy.
• Hepatitis B coinfection, which changes the choice of regimens.
• Kidney function and other baseline tests, according to the protocol.
• Mental health and use of other substances, which influence adherence.

The fictional example, again

Back to the woman from the opening: she was at the service for an abscess, on methadone treatment, with a regular connection. The phrase "treat when abstinent" postponed a decision that the evidence supports. An alternative reading of the same consultation would be to offer hepatitis C and HIV tests during the dressing change, collect the confirmatory test at the same moment, arrange delivery of the result at the next methadone dose and, if hepatitis C is confirmed, start treatment integrated into the agonist routine. The difference between the two approaches lies less in technical knowledge and more in the way of reasoning about the person.

When the person disappears from follow-up

Missed visits and interruptions happen. The person may be arrested, move address, lose their phone or go through a period of more intense use. Returning after an absence is a moment of welcome, not of reproach. Resuming treatment, checking what was taken and repeating the necessary tests is usually more useful than starting the assessment from scratch. A clear record of what was done helps any professional continue from where the person stopped.

Integrate instead of referring

People who use drugs often have several needs at the same time: treatment of the use disorder, wound care, mental health, hepatitis C, HIV and social issues. Each referral to a different service is a new chance of loss. Integrating as much as possible into the service the person already attends, such as the unit that provides the agonist, reduces travel and keeps the connection. The 2022 WHO recommendations follow this direction by proposing decentralization and integration of hepatitis C care (WHO, 2022). The post on differential diagnosis with clues reminds us that looking at the whole picture is part of the reasoning, and the same idea applies to care.

The biases that make the doctor postpone

The main delays in the care cascade of people who use drugs come from beliefs that seem prudent but that the evidence has already revised.

Desert bias. The idea that treatment should be reserved for those who have "proven" abstinence. The SIMPLIFY and C-EDGE CO-STAR trials show that drug use is compatible with cure.

Omission bias. Postponing seems safer than acting, even when the delay allows progression of liver disease and transmission.

Self-fulfilling prophecy. The professional believes the person will abandon treatment, offers less support and the abandonment happens.

Anchoring on the complaint. The consultation for an abscess ends at the abscess, and the test is left for later.

Affective bias. Discomfort with drug use reduces the willingness to explain, agree and follow up.

Pat Croskerry describes these shortcuts among the cognitive errors that affect clinical decisions (Croskerry, 2003). The post on affective bias explains how the professional's emotions change the reasoning, and the post on examples of heuristics in clinical reasoning organizes the shortcuts that lead to postponing.

A simple strategy against these biases is the opportunity question: "what can this person receive today that they may not receive on another visit?". It makes each contact a chance to test, treat or prevent, and reminds us that the next consultation may not happen.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues. You propose a diagnosis by looking for the ICD-10 code and receive feedback on proximity in five levels, which shows whether the guess landed on the exact code, the same category, the same group, the same chapter or a different chapter. This format connects with the theme of this text: the clue that changes the diagnosis is sometimes in a data point nobody asked for, such as a routine test that was left for later.

To use the case of the day as training, try three habits. Before each guess, ask which simple test would change the probability of the hypothesis. When the main complaint seems to explain everything, ask what else the person might have. After the result, note which clue you stopped looking for.

Three exercises with cases

Look for the missed opportunity. In each case, note at what point a routine test could have been offered.

Rewrite the decision to postpone. For a fictional case with the phrase "treat when abstinent", rewrite the decision based on the evidence.

Plan adherence. For a fictional person in treatment with an agonist, write how you would combine taking the antiviral with their routine.

The post about learning based on clinical cases shows why training with cases helps consolidate this type of decision.

The limits on using the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information on Curator and on Creators, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

Can people who use drugs treat hepatitis C?

Yes. Clinical trials showed high cure rates with direct-acting antivirals in people with recent injection drug use and in treatment with an agonist, and the guidelines recommend offering treatment regardless of current use.

How do you confirm active hepatitis C?

In general, the antibody test is followed by the viral RNA test, which confirms active infection. Collecting both steps at the same time reduces losses, according to the service protocol.

What to do when the person misses doses?

Talk about what happened, agree on strategies for the next doses and follow the guideline for missed doses. Incomplete adherence is part of treatment management.

Does reinfection mean treatment was useless?

Reinfection is a clinical finding. The meta-analysis by Hajarizadeh and colleagues showed lower rates than those of primary infection and recommended testing after treatment and access to harm reduction. The person can be treated again.

When to start antiretroviral therapy after an HIV diagnosis?

The START trial showed a net benefit of immediate start, and a systematic review showed that rapid start, including same-day start, improves viral suppression and retention in care.

Is PrEP for people who inject drugs?

The Bangkok Tenofovir Study showed a reduction in HIV infection with daily oral tenofovir in people who inject drugs. PrEP is part of the conversation along with the other prevention measures.

Final checklist

• I offered hepatitis C and HIV testing as routine, at this contact.
• I collected the confirmatory test at the same time, when the service allowed it.
• I offered hepatitis C treatment regardless of current use.
• I combined taking the antiviral with the person's routine and the treatment with an agonist.
• I explained that reinfection can happen and agreed on periodic testing.
• I discussed rapid start of antiretroviral therapy or PrEP, according to the result.

Want to practice reasoning with progressive clues? Play the case of the day.

References

1. AASLD-IDSA. Simplified HCV Treatment for Treatment-Naive Adults Without Cirrhosis. 2023. hcvguidelines.org.
2. Bhattacharya D, Aronsohn A, Price J, et al. Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2023. PMID 37229695.
3. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013. PMID 23769234.
4. Croskerry P. The importance of cognitive errors in diagnosis and strategies to minimize them. Acad Med. 2003. PMID 12915363.
5. Cunningham EB, Hajarizadeh B, Amin J, et al. Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs. Clin Infect Dis. 2021. PMID 32166305.
6. Dore GJ, Altice F, Litwin AH, et al. Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy: A Randomized Trial. Ann Intern Med. 2016. PMID 27537841.
7. Ford N, Migone C, Calmy A, et al. Benefits and risks of rapid initiation of antiretroviral therapy. AIDS. 2018. PMID 29112073.
8. Grebely J, Dalgard O, Conway B, et al. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018. PMID 29310928.
9. Hajarizadeh B, Cunningham EB, Valerio H, et al. Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis. J Hepatol. 2020. PMID 31785345.
10. INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015. PMID 26192873.
11. Kelly JF, Westerhoff CM. Does it matter how we refer to individuals with substance-related conditions? A randomized study of two commonly used terms. Int J Drug Policy. 2010. PMID 20005692.
12. Schillie S, Wester C, Osborne M, et al. CDC Recommendations for Hepatitis C Screening Among Adults, United States, 2020. MMWR Recomm Rep. 2020. PMID 32271723.
13. World Health Organization. Updated recommendations on simplified service delivery and diagnostics for hepatitis C infection. 2022. who.int.