- ARV Drug Introduction
- ARV Drug Classification
- ARV Drug Summary
- ARV Drug Paediatric Dosing Guidelines
- ARV Drug Toxicity
Once you have read this section you will be familiar with the four classes of ARV drugs and the points at which they target HIV in the life cycle. An overview of each drug has been provided along with a PDF version of the manufacturer’s package insert.
You will also become familiar with the current paediatric dosing guidelines and management of drug toxicities.
ARV Drug Classification
- when viral RNA is changed to DNA (reverse transcriptase inhibitor),
- when viral proteins are processed (protease inhibitor),
- when the virus binds to receptors on the human cell (entry inhibitor),
- when viral DNA is incorporated into cellular DNA (integrase inhibitor).
We have included only FDA approved drugs, however, new drugs that target other stages of the virus replication cycle are constantly in development.
Reverse Transcriptase Inhibitors
These drugs interfere with the conversion of viral RNA to DNA by the HIV reverse transcriptase enzyme inside the cell that has been infected.
There are two classes of reverse transcriptase inhibitors:
These are drugs that mimic the natural building blocks of DNA (nucleotides), however, once incorporated into the DNA chain by the HIV reverse transcriptase enzyme they do not allow additional nucleotides to be added and are hence named chain terminators or nucleotide base analogues.
Chain terminators can be free of phosphate groups and are referred to as Nucleoside Reverse Transcriptase Inhibitors (NRTI) or they can contain phosphate groups and are referred to as Nucleotide Reverse Transcriptase Inhibitors (written NtRTI). Once inside the cell they require three phosphate groups to be added to generate a nucleotide triphosphate which is the active form of the drug and is used as a substrate for reverse transcriptase during reverse transcription of viral RNA.
2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
These are drugs that bind directly to the HIV reverse transcriptase enzyme and prevent it from changing viral RNA to DNA.
Download NRTI Guide
Protease Inhibitors (PI)
Download Protease Inhibitors Guide
These drugs prevent entry of the virus into the human cell by interfering with binding of the virus to receptors on the cell surface. These drugs can either target the virus (ie. envelope proteins gp120 and gp41) or the cell receptors (ie. CD4 and CCR5/CXCR4).
There are currently two entry inhibitors that are FDA approved and they fall into two subclasses:
- Fusion inhibitors – Example: Enfuvirtide (binds to HIV gp41)
- CCR5 antagonists – Example: Maraviroc (PDF) (binds to CCR5)
Download Entry Inhibitors Guide
These are drugs that bind to the HIV integrase enzyme and prevent it from incorporating viral DNA into cellular DNA.
Example of an II is: Raltegravir
Download Integrase Inhibitors – Raltegravir Guide
ARV Drug Summary
Currently approved drugs for the treatment of HIV
Our quick-reference guide has been designed to give you a comparison of all the currently available antiretrovirals for the treatment of HIV. For your interest we have included dosing, side effects, warnings & and any additional considerations such as dietary advice and restrictions. We work consistently to keep this information up to date to ensure you always have access to the latest information.
Download Currently Approved Drugs for HIV
Paediatric Dosing Guidelines
Download Pediatric Dosing Guidelines – Selected ARV’s
ARV Drug Toxicity
1. Determine the seriousness of the toxicity.
2. Evaluate concurrent medications and establish whether the toxicity is attributable to an ARV drug or to a non-ARV medication taken at the same time.
3. Consider other disease processes (e.g. viral hepatitis in a child on ARV drugs who develops jaundice) or immune reconstitution syndrome, because not all problems that arise during treatment are caused by ARV drugs.
4. Manage the adverse event according to severity. In general:
- Severe life-threatening reactions: Immediately discontinue all ARV drugs, manage the medical event (i.e. symptomatic and supportive therapy) and reintroduce ARV drugs using a modified regimen (i.e. with an ARV substitution for the offending drug) when the patient is stabilized
- Severe reactions: Substitute the offending drug without stopping ART.
- Moderate reactions: Consider continuation of ART as long as feasible. If the patient does not improve on symptomatic therapy, consider single-drug substitutions. For a few moderate toxicities (e.g. peripheral neuropathy or lipodystrophy) single drug substitution needs to be considered earlier.
- Mild reactions are bothersome but do not require changes in therapy.
5. Stress the maintenance of adherence despite toxicity for mild and moderate reactions.
6. If there is a need to discontinue ART because of life-threatening toxicity, all ARV drugs should be stopped until the patient is stabilized.
Reference: WHO guidelines ANTIRETROVIRAL THERAPY FOR HIV INFECTION IN INFANTS AND CHILDREN: TOWARDS UNIVERSAL ACCESS.