HIV in Canada: A primer for service providers

 

Drug Resistance

Key Points

  • Poor adherence can lead to drug resistance.
  • Drug resistance is one of the main reasons for drug treatment failure.
  • Drug resistance can be transmitted.

While replicating in the body, HIV is also constantly changing, and mutations in the genetic material (viral RNA) occur regularly. The more viral replications, the more mutations can occur. Most of these mutations are harmless, but sometimes they can result in virus that is drug resistant.

Poor adherence is one of the key factors in the development of drug resistance. When someone doesn’t take their antiretroviral therapy as prescribed, the virus is more likely to replicate. This gives the virus more chances to create mutations. If one of these mutations blocks an antiretroviral drug from working the way it is supposed to work, the virus becomes harder to control. Drug resistance develops when this newly mutated virus can no longer be controlled by the antiretroviral drug and becomes the dominant virus in the body.

Once someone’s virus has developed resistance to a particular drug or group of drugs, the individual should no longer use those drugs because the drug is no longer effective.

If HIV develops resistance to one drug, it may also develop resistance to other drugs in the same class, regardless of whether the person has ever taken those drugs. This is known as cross-resistance.

Different types of resistance testing are available to determine whether an individual’s virus has developed drug resistance: genotypic and phenotypic testing. Genotypic tests are routinely used to identify drug resistance. They identify specific mutations in the virus that can lead to resistance to a particular drug. A phenotypic test measures the amount of drug needed to deactivate a sample of virus: the more drug that is needed, the more resistant the virus is. Phenotypic tests are not commonly used because they are considerably more difficult to run and few laboratories offer them.

An individual’s treatment choices become more limited as the virus develops resistance to different medications, and managing side effects and supporting adherence become increasingly important. The development of new drugs and classes of drugs is important for people with HIV who have resistance to most or all existing medications. However, even the newer drugs may be prone to resistance. Susceptibility to resistance is often dependent on what class a drug belongs to. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase inhibitors generally are more susceptible to resistance while protease inhibitors generally are less susceptible.

Transmission of drug-resistant HIV can occur in countries where HIV drugs are widely available. If someone has a drug-resistant strain of HIV, this can be transmitted to an HIV-negative person (primary drug resistance) or to someone already infected with another strain of HIV (superinfection). This can complicate and limit the treatment options for newly infected and re-infected individuals.

With the introduction of pre-exposure prophylaxis (PrEP,) strains of HIV with resistance to the drugs in PrEP (currently tenofovir DF and emtricitabine) can lead to PrEP failure (HIV infection) when people are adhering to the dosage schedule. This is rare, but cases have been documented.

Resources

Adherence and Resistance

Drug resistance and resistance testingYour Guide to HIV Treatment

Sources

  1. The Body. HIV drug resistance. Available from: http://www.thebody.com/index/treat/resistance.html
  2. Public Health Agency of Canada (PHAC). Update on HIV-1 Strain and Transmitted Drug Resistance in Canada: 2012-2013.  Ottawa: Centre for Communicable Disease and Infection Control, Public Health Agency of Canada; 2017. Available from: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/hiv-canadian-strain-drug-resistance-surveillance-2012-2013.html
  3. Major C. Resistance assistance: the ins and outs of HIV drug resistance testing. The Positive Side. Fall/Winter 2005. Available from: http://www.catie.ca/en/positiveside/fallwinter-2005/resistance-assistance
  4. Knox DC, Tan DH, Harrigan PR, et al. HIV infection with multi-class resistance despite pre-exposure prophylaxis (PrEP). Conference on Retroviruses and Opportunistic Infections (CROI), 22–25 February, 2016. Abstract 169aLB.
  5.  Grossman H et al. Newly Acquired HIV-1 Infection with Multi-Drug Resistant (MDR) HIV-1 in a Patient on TDF/FTC-based PrEP. HIV Research for Prevention (HIVR4P) 2016 conference, Chicago, October 2016, abstract OA03.06LB.