Guest Author - Jontay Watson
The focus of this article is to educate you on what HIV are available and how they work. In order to understand how HIV medicines work; you must first understand the HIV life cycle.
The HIV life cycle.
Like any virus, the HIV life cycle has a set method of how it is constructed. Unlike most virus', the HIV life cycle is rather intricate. The HIV life cycle is broken up until several different phases.
Once HIV is in the body, it targets and infects the CD4 cell. HIV then "hijacks" these cells and turns them into HIV factories that produce thousands of copies of the virus.
The HIV life cycle:
Step one and two: Binding and Fusions- HIV begins to enter a CD4 cell by binding (or attaching) itself to a specific point, called a CD4 receptor, on the cell's surface. HIV must then bind to a second co-receptor, either the CCR5 co-receptor or the CXCR4 co-receptor. This allows the virus to join with the CD4 cell in a process called fusion. After fusion, HIV releases its RNA (genetic material) and enzymes (proteins that cause chemical reactions) into the CD4 cell.
Step Three: Reverse Transcription - HIVs RNA contains the "instructions" that will reprogram the CD4 cell so that it produces more viruses. In order to be effective, HIVs RNA must be changed into DNA. An HIV enzyme called reverse transcriptase changes the HIV RNA to HIV DNA. HIV is the only virus that allows itself to be copied on top of itself. This is how the RNA fools the nucleus into thinking that it is DNA.
Step Four: Integration- The newly-formed HIV DNA enters the nucleus (command center) of the Cd4 cell. Another HIV enzyme called integrase combines or integrates HIVs DNA with the CD 4 cell's DNA.
Step Five: Transcription - Once the virus has become part of (is integrated into) the CD4 cell, it commands the Cd4 cell to start making new HIV proteins. The proteins are the building blocks for new HIV viruses. They are produced in long chains.
Step Six: Assembly - HIV enzyme called protease cuts the long chains of HIV proteins into smaller pieces. As the smaller protein pieces come together with copies of HIV's RNA, a new virus is assembled.
Step Seven: Budding - The newly-assembled virus pushes ("buds") out of the original CD4 cell. This new virus is now able to target and infect other CD4 cells.
Different classes of HIV drugs block different steps of the HIV's lifecycle:
* Entry Inhibitors: These drugs stop (inhibit) HIV from entering a CD4 cell. There are different types of entry inhibitors: fusion inhibitors and CCR5 antagonists. One of each type is approved:
Fusion inhibitor: Fuzeon (Enfuvirtide or T-20)
CCR5 antagonist: Selzentry (maraviroc)
* Integrase Inhibitors: These drugs interfere with HIV's integrase enzyme. There is one approved integrase inhibitor:
* Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs or "nukes")
These drugs interfere with the HIVs reverse transcriptase enzyme. There are a number of NRTIs:
Intelence (etravirine or TMC-125)
* Protease Inhibitors (PIs): These drugs interfere with the HIVs protease enzyme. There are many approved PIs:
Kaletra (lopinavir plus ritonavir)
Prezista (darunavir or TMC-114)
*Fixed-Dose Combinations: Although not a separate class, there are fixed dose formulations that combine two or more HIV drugs from one or more classes in just one pill. This can make dosing easier. There are five combination pills approved:
Atripla (Sustiva plus Emtriva plus Viread)
Combivir (Retrovir plus Epivir)
Epzicom (Epivir plus Ziagen)
Trizivir (Retrovir plus Epivir plus Ziagen)
Truvada (Emtriva plus Viread)
In order to be effective, doctors often give more than one drug from one or more classes in order to combat HIV at different phases. This is because HIV mutates when it reproduces. Certain mutations prevent certain HIV drugs from working. When this happens, HIV has become more resistant to a particular HIV drug.
If you take only one drug (monotherapy) or take a few drugs that all belong to one class, it is easy for HIV to develop mutations that make it resistant to that drug or drug class. However, if you take a combination of drugs from different classes, HIV has a much harder time mutating enough to develop drug resistance.