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Antiretroviral Drugs

Antiretroviralia

For medical students2 min readUpdated 2026-10-10

Antiretrovirals are used to disrupt the life cycle of the human immunodeficiency virus (HIV). They act at various stages of viral reproduction by blocking key enzymes and cell entry processes.

HIV FamilyRetroviridae (RNA viruses)
Life CycleConsists of 8 consecutive stages
Key EnzymesReverse transcriptase, integrase, protease
Main ClassesNucleoside and non-nucleoside inhibitors

HIV Characteristics and Life Cycle

The human immunodeficiency virus is an RNA-containing retrovirus. Successful pharmacotherapy requires targeting all eight stages of its reproduction. The viral life cycle begins with adsorption, where the gp120 glycoprotein and CD4 receptors with the CCR5 coreceptor mediate attachment to the target cell surface. This is followed by penetration—the fusion of the virion envelope with the cell membrane.

Inside the cell, reverse transcription takes place, during which double-stranded DNA (the provirus) is synthesized using viral RNA as a template. This process is catalyzed by the enzyme reverse transcriptase. The synthesized DNA enters the host cell nucleus, where integrase facilitates its insertion into the human genome. The integrated provirus can remain inactive for years, creating a risk of recurrence.

Protein Synthesis and Viral Maturation

Following integration, viral genetic information is expressed via transcription of the proviral DNA into mRNA and the synthesis of new viral RNAs. Ribosomes translate the mRNA into precursor viral proteins. The provirus encodes three critically important groups of proteins:

During the final stages of assembly and budding, the viral particle is formed. In the maturation process, the viral protease cleaves long polypeptide chains into individual functional proteins, rendering the new virion infectious.

Targets of Antiretroviral Therapy

Pharmacological intervention aims to block key steps in viral reproduction. Primary targets include viral enzymes and the cell entry process:

  1. Early stages: Blockade of the CCR5 coreceptor (Maraviroc) and inhibition of fusion (Enfuvirtide).
  2. Genetic material synthesis: Inhibition of reverse transcriptase (Zidovudine) and integrase (Raltegravir).
  3. Late stages and maturation: Inhibition of HIV protease (Indinavir, Ritonavir).

Widely used drug classes include structural analogues of nucleosides and nucleotides, as well as non-nucleoside reverse transcriptase inhibitors.

Mnemonic

The order of viral enzyme action is easily remembered by the acronym "RIP": Reverse transcriptase builds DNA, Integrase inserts it into the genome, and Protease cleaves proteins for maturation.

Frequently asked questions

Which drugs belong to the HIV protease inhibitors?

HIV protease inhibitors include saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, darunavir, and fosamprenavir. Combination formulations containing lopinavir and ritonavir are also used. These agents act during the late stage of viral replication and prevent viral maturation.

  • Saquinavir — the first representative of the protease inhibitor class.
  • Ritonavir — an agent frequently used as a pharmacokinetic booster.
  • Lopinavir — used in fixed-dose combinations with ritonavir.
Which receptors and coreceptors are involved in HIV adsorption?

During HIV adsorption, the virus attaches to the target cell surface using key structural components, engaging the viral glycoprotein gp120 alongside specific cellular receptors and coreceptors.

  • CD4 — the primary host cell receptor.
  • CCR5 — a chemokine coreceptor.
  • CXCR4 — a chemokine coreceptor.
Which medications belong to the nucleoside reverse transcriptase inhibitors (NRTIs)?

NRTIs are structural analogues of natural nucleosides and nucleotides. They inhibit viral DNA synthesis during the early stage of replication.

  • Zidovudine — a thymidine analogue.
  • Abacavir — a guanosine analogue.
  • Lamivudine — a cytidine analogue.
  • Emtricitabine — a cytidine analogue.
  • Tenofovir — an adenine nucleotide analogue.
How do nucleoside reverse transcriptase inhibitors differ from non-nucleoside inhibitors?

The differences between these NRTI and NNRTI classes lie in their chemical structure and their mode of interaction with reverse transcriptase.

ParameterNucleoside Inhibitors (NRTIs)Non-Nucleoside Inhibitors (NNRTIs)
StructureModified structure (nucleoside and nucleotide analogues)Not detailed in the source text
MechanismIncorporate into the growing viral DNA chain and cause chain terminationNot detailed in the source text
What adverse effects are associated with zidovudine?

Zidovudine is associated with several serious side effects and toxicities that require close patient monitoring.

  • Hematologic abnormalities (myelosuppression) — bone marrow suppression presenting as anemia, neutropenia, leukopenia, and thrombocytopenia.
  • Mitochondrial toxicity — inhibition of mitochondrial DNA synthesis, leading to myopathy.
  • Hepatotoxicity — potential development of hepatic steatosis and acidosis.
  • Neurotoxic and systemic reactions — headache, insomnia, agitation, paresthesias, dyspepsia, skin rash, and fever.
What family of viruses does HIV belong to?

The human immunodeficiency virus belongs to the Retroviridae family and is an RNA virus.

What role does reverse transcriptase play?

Reverse transcriptase (an RNA-dependent DNA polymerase) drives reverse transcription—the synthesis of double-stranded DNA (the provirus) using viral RNA as a template.

What groups of proteins does proviral DNA encode?

The provirus encodes three groups of proteins: enzymes (reverse transcriptase, integrase, protease), polypeptide precursors, and the gp160 transmembrane protein.

What are the targets of Maraviroc and Raltegravir?

Maraviroc blocks the CCR5 coreceptor during viral adsorption, while Raltegravir inhibits integrase during the integration of viral DNA into the host genome.

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