There is currently no safe and effective cure for HIV, but scientists are working hard to find one and are hopeful. There are different types of drugs that have been used and are still used to try to treat HIV and AIDS. Let’s see what these drugs are and how they work.
The HIV virus is a retrovirus. This means that its genetic material is RNA instead of DNA. Once the virus enters a CD4 cell, a type of immune cell in our body, it uses an enzyme called reverse transcriptase to implant its RNA genetic code into the DNA of the CD4 cell. It also codes for the production of HIV RNA, which is used to create daughter viruses from the very DNA it has just disrupted. The HIV virus also prompts the invaded cell to use its own DNA to signal the production of proteins and enzymes essential for the survival of the HIV virus.
Moreover, by implanting its RNA into the DNA of the CD4 cell, it is also able to transmit this genetic material to the newly divided CD4 cells. By the way, the virulence potential of HIV-1 is illustrated by its incredibly rapid genetic change over a short period of time. It evolves a million times faster than mammalian DNA.
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AZT for the treatment of HIV
How much progress have we made in dealing with this terrible disease? The first drug breakthrough came when Jerome Horwitz, a scientist studying cancer, developed Zidovudine, also known as AZT. In 1964, it was originally designed for use as a cancer medicine, but this was unsuccessful. Twenty-five years later, other scientists surprisingly discovered that it had antiretroviral activity, and it became the first antiretroviral drug. It was the first treatment to give hope to HIV-positive patients.
The first nationally sponsored HIV drug trials took place in the 1980s, where AZT was compared to a placebo. Patients had to set their watches in the middle of the night to take their medication every four hours. While AZT was shown to be effective, it only slightly weakened the viral load in the blood. AZT reduced the viral load by a logarithm, for example, from one million to 100,000 viral particles. In addition, when used alone, resistance has quickly developed. Additionally, AZT was not without several significant side effects, most notably nausea.
However, due to the crisis state of the HIV and AIDS pandemic, and for humanistic reasons, this drug was approved within 20 months, instead of the usual 8-10 years.
Learn more about the life cycle of a virus.
There are six classes of antiretroviral drugs currently in use, corresponding to six targets in the HIV virus replication cycle. When the virus begins to replicate, HIV must enter the host cell.
Entry inhibitors and fusion inhibitors work to block this attachment and movement in the cell. A receptor on the cell membrane known as CCR5 is crucial for the viral attachment of HIV. The virus’s RNA is guided into the host’s DNA by an enzyme called integrase. Integrase inhibitors are another weapon to restrict viral replication.
NRTI and NNRTI Drugs
Classes of drugs called NRTI and NNRTI focus their attention on the most important enzyme in the synthesis of RNA and DNA, reverse transcriptase. NRTI stands for Nucleoside Reverse Transcriptase Inhibitors, and are the oldest therapies, and include AZT. They are nucleoside analogs or the building blocks of DNA.
But they lack an oxygen and hydrogen atom in the basic sugar structure, so once they are incorporated into the replicated viral DNA, the reverse transcriptase enzyme is forced to terminate the addition of more amino acids and stops the synthesis of proteins and enzymes.
Another class of ART, known as NNRTI, also inhibits the enzyme reverse transcriptase, but it accomplishes this task by physically getting in the path of the enzyme to block DNA synthesis.
Combination of drugs
Another class of drugs are known as protease inhibitors, and they work by binding to the protease in HIV. This enzyme is responsible for allowing the virus to exit the host cell. This leads to the inability of the HIV virus to come out.
By combining drugs from different classes, we are able to suppress viral replication at different points in the life cycle of HIV. For example, combining nucleoside analogs with different drugs that mimic the structure of DNA increases the chances of viral reverse transcriptase blocking. A combination of at least three antiretroviral drugs at once is the current standard of care.
Learn more about the dynamic world of infectious diseases.
Review ART regimens
The recommended first- and second-line ART regimens are reviewed almost every 6 months and must be published online due to rapid changes in the science of ART. The goal of combination therapy is a 3 to 5-fold log reduction in blood viral load, attempting to reduce the viral load to less than 100, and even to undetectable levels. However, the virus is still present in the body in lymph nodes and other sites known as hidden sanctuaries.
Since there are between one and 10 billion HIV viruses that replicate daily, there is a large and rapid turnover of genetic material, and therefore a high probability of emergence of the potential for mutant drug-resistant viruses. HIV reverse transcriptase also has a high error rate in reading its genetic code, which increases the potential for mutations and drug resistance.
Mutations and drug development
Finally, if patients do not stick to all doses of their medications, it can lead to sub-therapeutic drug levels, which greatly increases the risk of drug mutations. In fact, the chances of being infected with an HIV virus without mutations that code for drug resistance are increasingly rare.
You should know that sometimes the mutant HIV virus is not necessarily more virulent. In fact, the mutant virus may be weak enough that it does not have a long-term survival advantage, and therefore becomes clinically insignificant. The capacity for rapid mutations reinforces the need for continued aggressive pharmaceutical development in the field.
Common questions about HIV treatment and antiretroviral therapy
HIV uses an enzyme called reverse transcriptase to implant its RNA genetic code into the DNA of the CD4 cell. It also codes for the production of HIV RNA, which is used to create more viruses. The virus also prompts the invaded cell to use its own DNA to signal the production of proteins and enzymes essential for the virus to survive.
In 1964, AZT was a failed cancer drug. Twenty-five years later, other scientists surprisingly discovered that he had anti-retroviral and it became the first antiretroviral drug to be used to treat HIV.
There are six classes of Antiretroviral drugs currently in use, corresponding to six targets in the HIV virus replication cycle.