Antiretrovirals and HIV

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Introduction[edit | edit source]

Goals of antiretroviral therapy[edit | edit source]

The key goals of antiretroviral therapy are to[1]:

  • to prevent HIV from multiplying
  • achieve and maintain suppression of plasma viremia to below the current assays’ level of detection;
  • improve overall immune function as demonstrated by increases in CD4+ T cell count;
  • prolong survival;
  • reduce HIV associated morbidity;
  • improve overall quality of life; and
  • reduce risk of transmission of HIV to others

It is important to remember that current antiretroviral regimens do not eradicate HIV; viral rebound occurs rapidly after treatment discontinuation, followed by CD4 decline, with potential for disease progression. It is essential to strictly follow the prescribed regimen to avoid viral rebound and the potential for selection of drug resistance mutation. A combination regimen should consist of preferably 3 (but at least 2) active agents based on genotype resistance test results.[1]

Antiretroviral drugs[edit | edit source]

There are six classes of drugs used in antiretroviral therapy[2]:

  • nucleoside reverse transcriptase inhibitors (NRTI): They compete with natural deoxynucleotides for incorporation into a growing viral DNA chain. However, NRTIs lack a 3'-hydroxyl group on the deoxyribose moiety. This difference results in incorporating an NRTI, and the next incoming deoxynucleotide cannot form the following 5', 3' phosphodiester bond needed to extend the DNA chain. The result is a chain termination in DNA synthesis. Names of FDA approved drugs: Abacavir, emtricitabine, lamivudine; Tenofovir disoproxil fumarate, zidovudine
  • non-nucleoside reverse transcriptase inhibitor (NNRTI): They block reverse transcriptase (RT) by directly binding to the enzyme. Though NNRTIs do not get incorporated into the viral DNA, they inhibit the movement of protein domains of RT that are essential to carry out the DNA synthesis. Name of FDA approved drugs-Efavirenz, etravirine, nevirapine, rilpivirine
  • protease inhibitor (PI): Bind HIV-1 protease and block proteolytic cleavage of protein precursors necessary for the production of viral particles. Name of FDA approved drugs: Atazanavir, darunavir, fosamprenavir, ritonavir, saquinavir, tipranavir
  • integrase inhibitor (II): Block the action of integrase, preventing the viral genome from inserting itself into the DNA of a host cell. Name of FDA approved drugs

Sub Heading 3[edit | edit source]

Resources[edit | edit source]

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References[edit | edit source]

  1. 1.0 1.1 Pau AK, George JM. Antiretroviral therapy: current drugs. Infectious Disease Clinics. 2014 Sep 1;28(3):371-402.
  2. Kemnic TR, Gulick PG. HIV antiretroviral therapy. StatPearls [Internet]. 2020 Jun 23.