Prepared by: Bratislav Prokić, July 2022
Review: Dr. Jovana Milić,
Metabolic clinic for HIV in Modena, Italy
Each class of HIV drugs attacks the virus in a different way. Understanding those mechanisms is not essential to successful treatment, so don’t be discouraged if the topic is too complex for you to understand.
How many groups of HIV drugs are there?
There are five main groups of antiretroviral (ART) drugs: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors (II), entry inhibitors (EI), protease inhibitors (PI). There are a few more groups that are used less frequently or are still under development.
How are these types of HIV drugs used in treatment?
Most people start therapy with two drugs from the group of nucleoside/nucleotide reverse transcriptase inhibitors, which they call backbone therapy, to which they add one drug from the groups of integrase, protease or non-nucleoside reverse transcriptase inhibitors.
One tablet does not mean one drug, because one tablet can contain combinations of two or more drugs.
How do nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs and NtRTIs) work?
Drugs from this group interfere with the HIV enzyme – reverse transcriptase in the conversion (transcription) of single-membered viral RNA into double-membered viral DNA. This class of drugs is often called the “backbone”, or the basis of the first line of therapy against HIV. This group of drugs includes: lamivudine, tenofovir, emtricitabine, abacavir and others.
How do non-nucleoside reverse transcriptase inhibitors (NNRTIs) work?
Drugs from the group of non-nucleoside reverse transcriptase inhibitors target the same enzyme as nucleoside/nucleotide inhibitors (NRTIs), but they do so by directly binding to it (reverse transcriptase enzyme) and thus disrupting the process of converting (transcription) RNA viruses into double-stranded viral DNA . Medicines from this group are: efavirenz, rilpavirine, nevirapine and others.
How do integrase inhibitors (II) work?
Drugs from this group interfere with the HIV enzyme integrase to integrate the processed double-stranded viral DNA into the DNA of the host (into human cells). This group of drugs includes: raltegravir, dolutegravir, bictegravir and others.
How do protease inhibitors (PIs) work?
Drugs from this group block the activity of the protease enzyme, which breaks down large polyproteins into smaller parts, needed to assemble new viral particles. Medicines from this group are: darunavir, lopinavir and others. These drugs are always accompanied by auxiliary drugs – boosters, which make the liver break down the primary drug more slowly, so that it stays in the body longer. Boosters are: cobicistat and ritonavir.
How do entry inhibitors (EIs) work?
There are two types of drugs that prevent HIV from entering a human cell: fusion inhibitors and CCR5 inhibitors. A fusion inhibitor (drug: enfuvirtide) stops the fusion of the HIV envelope protein with the CD4 cell. This medicine is given by injection and is therefore rarely used. CCR5 inhibitor (drug: maraviroc) blocks this co-receptor. Because in some people HIV can bind to another, CXCR4 receptor, a special test must be done before giving this medicine.
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