On transmitted drug resistance

27 Oct

I work on drug resistance in HIV. There are two ways in which someone can end up with a drug-resistant HIV strain. Either you were infected with a non-resistant strain and subsequently the virus evolved to become drug resistant while you were taking treatment. This is called “acquired drug resistance.” The other possibility is that you got infected with a viral strain that was already resistant. This is referred to as “transmitted drug resistance.” Most of my work deals with the first type of resistance (acquired), this blog post, however, deals with the second type (transmitted).

Transmitted drug resistance is a serious problem, because people with transmitted drug resistance may start a treatment that is not going to work. Worse: if you take a treatment that doesn’t work very well –because your virus is resistant of one or more of the drugs you take– then it is likely that your virus will soon evolve to become resistant to the other drugs you’re taking. This sort of trouble can be avoided if a resistance test is done before treatment is started.

To explain the basics of transmitted drug resistance, I made a short video about it. Have a look!

The science behind the movie

If you’d like to know more about transmitted drug resistance, keep on reading! I took the rest of the text in this post from my review paper “HIV drug resistance, problems and perspectives” that appeared in Infectious Disease Reports earlier this year (under a creative commons license 🙂 ).

Levels of transmitted drug resistance: substantial but not disastrous

Drug-resistant HIV strains can be transmitted from one patient to another. Due to such transmitted drug resistance, a newly infected patient may carry a drug-resistant virus even though he or she has not yet used antiretroviral drugs. From the early days of HIV treatment, researchers have feared that drug-resistant strains would reach high frequencies among newly infected patients, rendering certain drugs entirely useless. Fortunately, this has never happened with HIV drugs. In comparison, many malaria drugs have been withdrawn from use by national authorities because of widespread transmission of drug resistant malaria parasites (1). Transmitted drug resistance does occur in HIV, but the numbers have remained relatively low. In high-income countries, between 7 and 17% of newly infected patients carry at least one major drug-resistance mutation, usually a mutation that confers resistance to one of two drug classes: nucleoside reverse transcriptase inhibitors (NRTI) or non-nucleoside reverse transcriptase inhibitors (NNRTI) (2,3). The transmission of drug resistance to the third major drug-class (protease inhibitors, PIs) is less common.

Differences between high and low income countries

In middle and low-income countries, the levels of transmitted drug resistance are lower than in high-income countries, but this will likely change with time. In 2006, the member states of the United Nations agreed to aim for universal access to treatment in 2010 (4) The rapid increase of availability of ART in middle- and low-income countries following this decision is referred to as the rollout of ART. There is evidence for a rapid increase in transmitted drug resistance in the years after rollout of ART in east and southern Africa (5) This is not surprising, because ART went from being virtually non-existent to being quite common in these regions. The prevalence of transmitted drug resistance in middle- and low-income countries is estimated to be around 7% (2)

Genotyping is key

Even though transmitted drug resistance is somewhat more common in high-income countries than in low-income countries, the impact may be lower for patients in high-income countries. This is because, in high-income countries, it is standard practice to genotype the virus before starting treatment, to determine whether resistance mutations are present. If such genotyping is done and a fully active combination of drugs is chosen, treatment success rates of patients with transmitted drug resistance are very high. For example, Wittkop et al (6). estimated that among European patients with transmitted drug resistance who were treated with a fully active combination of drugs, 95% had fully suppressed viral load after one year. Of the patients who were treated with an insufficiently strong regimen, 85% had fully suppressed viral load after one year.

In low-income countries, patients with transmitted drug resistance may start insufficiently strong ART regimens, because viral genotyping is usually not available and transmitted resistance not detected. Insufficiently strong treatments will be less effective in reducing the viral load, which, in turn, can lead to the evolution of multi-class drug resistance. In addition, even if testing is done, fewer second-line treatment options are available for patients in low-income countries.

References

  1. Read AF, Huijben S. (2009). PERSPECTIVE: Evolutionary biology and the avoidance of antimicrobial resistance. Evol Appl 2009;2:40-51. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131826/
  2. World Health Organization. HIV drug resistance report 2012. Available from: http://apps.who.int/iris/bitstream/10665/75183/1/9789241503938_eng.pdf.
  3. Frentz D, Boucher CA, van de Vijver DA. Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the world. AIDS Rev 2012;14:17-27. http://www.ncbi.nlm.nih.gov/pubmed/22297501
  4. WHO, UNAIDS, UNICEF. Towards universal access. 2007. Available from: http://www.who.int/hiv/mediacentre/universal_access_progress_report_en.pdf.
  5. Gupta RK, Jordan MR, Sultan BJ, et al. Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis in resource limited settings 2001-2011. Lancet 2012;380:1250-8. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61038-1/abstract
  6. Wittkop L, Günthard HF, de Wolf F, et al. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. Lancet Infect Dis 2011;11:363-71. http://www.ncbi.nlm.nih.gov/pubmed/21354861
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