Heroin and other opioids
Opioids act on the central nervous system, producing pain relief, relaxation, and euphoria. The main risk is respiratory depression and overdose, which gets worse with other depressants and some antiretrovirals. Naloxone can reverse an overdose.
What are they?
Opioids are a family of substances that includes heroin, morphine, fentanyl, oxycodone, and other opioid-derived or synthetic pain medicines. They act on the central nervous system, producing analgesia (pain relief), relaxation, and euphoria.
The main opioid risk is respiratory depression and overdose, especially when they are combined with other substances or some medicines.
Do not share equipment or use supplies: needles, syringes, filters, spoons, and other items may transmit HIV, hepatitis C, and other infections.
How are they used?
- Injection (intravenous, intramuscular, or subcutaneous): fast and intense onset
- Inhaled or smoked (mainly heroin): slower onset than injection
- Oral use (pills or liquids, prescription opioids): slower onset
Injection carries the highest risk of overdose and infection transmission.
How do they work?
Opioids bind to opioid receptors (mu, kappa, delta) in the brain, spinal cord, and peripheral tissues, which can produce:
- Strong pain relief
- Sedation and deep relaxation
- Euphoria (especially with intravenous use)
- Reduced breathing reflex
- Constricted pupils (pinpoint pupils)
- Nausea and vomiting
At high doses, depression of the breathing centre may be fatal if there is no timely intervention.
They are mainly metabolised through the liver CYP450 system.
Interactions with antiretrovirals
Opioid interactions with antiretrovirals are especially important and may go in two opposite directions.
They INCREASE sedation, respiratory depression, and overdose risk
Protease inhibitors boosted with ritonavir or cobicistat (lopinavir/r, atazanavir/r, darunavir/r) inhibit the CYP450 enzymes responsible for metabolising many opioids. This may significantly increase opioid blood levels:
- Deep sedation and inability to wake up
- Respiratory depression: slow, shallow, or paused breathing (life-threatening)
- Greater overdose risk even with usual doses
They DECREASE analgesic effect and may trigger withdrawal
Efavirenz and, to a lesser extent, nevirapine induce the CYP450 system, speeding up opioid elimination. This may cause:
- Reduced expected pain relief
- Withdrawal symptoms in people with physical dependence
Important: any change in ART may change how opioids affect you. Talk with the healthcare team before changing treatment.
Medicines requiring more caution
| Group / Medicine | Interaction risk | Notes |
|---|---|---|
| PI boosted with ritonavir or cobicistat: lopinavir/r, atazanavir/r, darunavir/r | Very high | CYP450 inhibition; may raise opioid levels and overdose risk |
| Efavirenz | High | CYP450 induction; may lower opioid levels and trigger withdrawal |
| Nevirapine | Moderate | Similar inducing effect to efavirenz, though less pronounced |
| Other NNRTIs | Moderate | May have inducing effects depending on the specific drug |
| Cobicistat-based combinations | Very high | Cobicistat is a strong CYP3A4 inhibitor, similar to ritonavir |
Harm reduction
- Use the smallest amount possible
- NEVER combine with alcohol, benzodiazepines, GHB, or other CNS depressants (fatal overdose risk rises sharply)
- Wait at least 2 hours between doses to avoid accumulation
- Keep NALOXONE nearby and learn how to use it (it reverses opioid overdose; it is safe and can save lives)
- Do not use alone: if an overdose happens, someone needs to be able to ask for help and give naloxone
- Tell your healthcare team about opioid use, especially when changing ART
- Do not share equipment or use supplies
Naloxone: a life-saving antidote
Naloxone (Narcan®) quickly reverses opioid overdose. It is safe, does not affect people who do not have opioids in their body, and may be given:
- As a nasal spray
- By intramuscular injection
If you give naloxone and the person wakes up, still seek medical care: naloxone’s effect is shorter than the opioid’s effect, and more doses may be needed.
Warning signs
- Slow, shallow, or paused breathing
- Extreme sleepiness or difficulty waking up
- Very small pupils (pinpoint pupils)
- Bluish lips or nails (cyanosis)
- Loss of consciousness or no response to stimulation
When should you seek medical care?
- Trouble breathing or no response to stimulation
- Seizures
- Confirmed or suspected overdose (even if naloxone was given)
- Any unusual or persistent reaction
- Signs of infection at injection sites (redness, warmth, pus)
Call emergency services immediately for any sign of overdose.
Interaction table with sexual health medicines (Chapter 15)
| Medicine / Treatment | Pharmacological interaction | Does it affect adherence? | What may happen? | What to do? |
|---|---|---|---|---|
| ART (antiretroviral treatment) | Moderate in some regimens | May increase the risk of missed doses | Sedation, drowsiness; some regimens (for example with ritonavir or cobicistat) may increase heroin effects | Do not stop ART. Use reminders. Ask for help if you have excessive drowsiness or respiratory depression |
| PrEP (TDF/FTC, TAF/FTC) | Low | May increase the risk of missed doses | No major interaction. The main risk is forgetting doses | Set reminders. PrEP protects when taken consistently |
| Cabotegravir LA (PrEP injection) | Low | Does not affect it | No significant interactions have been reported | Keep your check-ups and injection appointments |
| PEP (TDF/FTC + raltegravir or dolutegravir) | Moderate | May increase the risk of missed doses | Nausea and discomfort may feel worse. Greater risk of not completing treatment | Complete the 28 days. If you vomit, ask what to do depending on the time that passed |
| Gender-affirming hormone therapy | Moderate | Does not affect it | Possible increase in sedation. It does not reduce hormonal effectiveness | Do not stop therapy. Use reminders and ask for help if you develop excessive drowsiness |
| Hepatitis B (tenofovir, entecavir) | Low | May increase the risk of missed doses | No major interaction | Do not stop treatment. Stay in regular follow-up |
| Hepatitis C (DAAs) | Moderate* | May increase the risk of missed doses | Some medicines may cause discomfort, nausea, and fatigue that may feel worse with heroin | Do not stop treatment. Ask for help if you have important adverse effects. *Depends on the specific medicine |
| Erection medicines (sildenafil, tadalafil) | Moderate | Does not affect it | Greater hypotension, dizziness, fainting, especially with injection and alcohol | Do not mix with alcohol or poppers. Hydrate and stand up slowly |
What does the evidence say?
Interactions between opioids and protease inhibitors boosted with ritonavir or cobicistat are well documented. Ritonavir is one of the strongest CYP3A4 inhibitors and may raise plasma levels of some opioids up to tenfold. Efavirenz, in contrast, speeds up opioid metabolism and may trigger withdrawal syndromes. These effects are especially relevant when starting or changing ART. Naloxone is available without prescription in some countries and is an essential part of harm reduction for people who use opioids.