HIV drug resistance

HIV drug resistance occurs when microevolution causes virions to become tolerant to antiretroviral treatments.

Potential limited effects of current drugs

HIV is considered resistant when it does not respond to known treatments.[1] Foe example - A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis. Dhurat R, Kothavade RJ, Kumar A. Indian J Med Microbiol. 2018 Jan-Mar;36(1):136-139. doi: 10.4103/ijmm.IJMM_16_330.

PMID 29735845 HIV drug resistance reduces the possible HIV medications a person can take due to cross resistance. In cross resistance, an entire medication class is considered ineffective in lowering a patient's HIV viral load because all the drugs in a given HIV class share the same mechanism of action.[2] Therefore, development of resistance to one medication in a class precludes the use of all other medications in the same class. A blood test should be done to determine which drugs may be effective prior to initiation of treatment or during treatment to ensure resistance has not developed.[2]

In 2004, one study estimated the percentage of the American HIV positive population with some form of drug resistance to be 76.3%.[3] Certain intrinsic features of HIV facilitate its widespread resistance, most importantly its extremely high mutation rate.

In their 2017 HIV Drug Resistance Report, the World Health Organization conducted surveys in 14 countries to estimate the prevalence of resistance to HIV medications. One subgroup included only HIV-positive patients who have just initiated antiretroviral therapy in order to assess the prevalence of HIV drug resistance in treatment-naive patients, deemed "pretreatment drug resistance." Resistance to NNRTIs in this patient population ranged from 2.7% (in Myanmar) to 15.9% (in Uganda). Resistance to NRTIs ranged from 0.3% (in Namibia) to 6.8% (in Nicaragua). Resistance to protease inhibitors ranged from 0.3% (in Carmeroon and Myanmar) to 2.6% (in Mexico). Resistance to NNRTI + NRTI combination therapy ranged from 0.2% (in Myanmar) to 4.6% (in Uganda).[4]

Developing resistance (less fit mutations compared to wild type)

As a retrovirus, HIV uses the enzyme reverse transcriptase to synthesize DNA from its RNA genome and lacks a mechanism for correcting errors made while reproducing its genome.[1] As a result, HIV replicates its genome with the highest known mutation rate of any 'living' organism.[1] This creates an ideal situation for natural selection to act on the HIV population, as genetic variation is the raw material for natural selection.

These mutations accumulate over generations and in populations, resulting in the great genetic variation within populations of HIV, and an increased probability of a virion developing an evolutionary selective advantage over other virions.[1] Natural selection then acts on HIV by selecting for virions with higher fitness, as all others are eventually killed off by drug treatments.[5] The virions that are able to escape the harmful effects of the drug then create an entirely new, drug resistant population.

The virions reproduce until the patient has a population of viruses as large as they originally did before treatment reduced these numbers. This creates a cycle in which patients first experiences success with treatment, as their viral levels decrease, then experiences a decline in treatment effectiveness as the virus develops resistance and rebuilds its population of virus particles.

Contemporary treatment issues

Exposure to antiretroviral treatments has led to the evolution of HIV in response to selection pressure that eliminates strains of HIV that do not express resistance mechanisms. Drug resistance occurs in all antiretroviral treatments if patients are non-adherent,[5] meaning that they do not take their medication regimens as prescribed. Lack of adherence may result from unreliable access to the medication, due to prohibitive cost or inadequate supply.[6]

Current medical and scientific opinion is mixed on the most effective treatment methods, but is focused on drug cocktails and the importance of first-line regimens.[7] The World Health Organization advocates a public-health approach to HIV treatment in order to make treatment uniform and available to patients around the world.[8] As of July 2017, the WHO is implementing the Global Action Plan on HIV drug resistance 2017-2021. It is a 5-year initiative intended to help countries around the world manage HIV drug resistance.

[9]

Among treatment methods, the World Health Organization acknowledges the importance of successful first-line treatments.[8] First-line treatments are known to affect the virus’ future response to other treatments, making the effectiveness of first-line treatments an issue of vital importance.[8] The most successful treatments are combinations of three drugs used simultaneously, as this greatly reduces the probability of the virus developing resistance.[10]

See also

References

  1. 1 2 3 4 Freeman, S., and J. C. Herron. 2007. Evolutionary Analysis. 4th ed. A case for evolutionary thinking: understanding HIV. Pearson Benjamin Cummings, San Francisco, CA.
  2. 1 2 "Drug Resistance". AIDSinfo. U.S. Department of Health and Human Services. Retrieved 31 October 2017.
  3. ↑ Richman, D. D., S. C. Morton, T. Wrin, N. Hellmann, S. Berry, M. F. Shapiro, and S. A. Bozzette. 2004. The prevalence of antiretroviral drug resistance in the United States. AIDS. 18: 1393–1401.
  4. ↑ "HIV drug resistance report. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO" (PDF).
  5. 1 2 Kozal, M.J. (2009-01-01). "Drug-resistant human immunodefiency virus". Clinical Microbiology and Infection. 15: 69–73. doi:10.1111/j.1469-0691.2008.02687.x. ISSN 1198-743X. PMID 19220361.
  6. ↑ "Adherence to HIV Antiretroviral Therapy". hivinsite.ucsf.edu. Retrieved 2017-11-01.
  7. ↑ "Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection". World Health Organization. Retrieved 2017-11-01.
  8. 1 2 3 Gilks, C. F., S. Crowley, R. Ekpini, S. Gove, J. Perriens, Y. Souteyrand, D. Sutherland, M. Victoria, T. Guerma, and K. De Cock. 2006. The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 368:505–510.
  9. ↑ "Global action plan on HIV drug resistance 2017–2021". World Health Organization. Retrieved 2017-11-01.
  10. ↑ Cane, P. A. 2009. New developments in HIV drug resistance. J Antimicrob Chemoth. 64 (Suppl.1): 37–40.
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