Pharmacokinetics of nucleoside/nucleotide reverse transcriptase inhibitors for the treatment and prevention of HIV infection

Expert Opin Drug Metab Toxicol. 2020 Jul;16(7):551-564. doi: 10.1080/17425255.2020.1772755. Epub 2020 Jun 7.


Introduction: Despite dramatic increases in new drugs and regimens, a combination of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) remains the backbone of many regimens to treat HIV.

Area covered: This article summarizes the pharmacokinetic characteristics of approved NRTIs that are currently in the international treatment and prevention guidelines.

Expert opinion: Compared to other NRTIs, tenofovir alafenamide fumarate (TAF) is more advantageous in terms of potency and safety. It is therefore a preferred choice in combination with emtricitabine (FTC) in most HIV treatment guidelines. The efficacy of the two-drug combination of NRTI/Integrase strand-transfer inhibitor, i.e. lamivudine/dolutegravir has been approved as an option for initial therapy. This regimen however has some limitations in patients with HBV coinfection. The two NRTI combinations tenofovir disproxil fumarate (TDF)/FTC and TAF/FTC have also been approved for pre-exposure prophylaxis (PrEP). Interestingly, a promising long-acting nucleoside reverse transcriptase translocation inhibitor, islatravir, formulated for implant was well tolerated and remained effective for up to a year, suggesting its potential as a single agent for PrEP. In the next decade, it remains to be seen whether NRTI-based regimens will remain the backbone of preferred ART regimens, or if the treatment will eventually move toward NRTI-sparing regimens to avoid long-term NRTI-toxicity.

Keywords: HIV; nucleoside reverse transcriptase inhibitors; nucleotide reverse transcriptase inhibitor; pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics
  • Coinfection
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Hepatitis B / epidemiology
  • Humans
  • Pre-Exposure Prophylaxis / methods
  • Reverse Transcriptase Inhibitors / administration & dosage*
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / pharmacokinetics


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors