Side-effect free, less toxic anti-HIV drug may well be underway.
Anti-HIV drugs with far less toxic side effects will soon be a reality as researchers at The University of Texas at Austin have pointed the way by discovering the atomic structure of a key human enzyme.
Several of the anti-HIV drugs currently in use are designed to stop the process of DNA replication. Because stopping the process of DNA replication of the HIV causing retrovirus these drugs can effectively stop the virus from multiplying and infecting newer cells in the body.
Current anti-HIV drugs, however, while targetting the replication of viral material, also affect human enzymes that perform similar functions in normal cells. Once the human enzymes which control the normal cell function the body is involved, it can lead to a number of harmful harmful drug side effects.
Now that researchers have solved the atomic structure of an enzyme, known as Pol ? (pol gamma), that is responsible for DNA replication in human mitochondria, this sort of unwanted side-effects of anti-HIV drugs could be avoided.
Pol gamma role in mediating the toxicity of the drugs is quite known. But it has been difficult to design a drug that can distinguish between HIV and pol gamma without knowing the structure of pol gamma. With the structures of both pol gamma and HIV known, the differences between the two can be exploited in the design of new drugs that will be more selective (and thus less toxic) against HIV, researchers said.
Mitochondria – also known as the powerhouse of a cell- produce most of the energy that sustains human cells. When pol gamma comes into contact with certain anti-retroviral drugs, however, it can incorporate the drug into mitochondrial DNA, and thus interfere with the normal replication process. This interferes with the ability of mitochondria to function. The consequences can range from simple nausea to bone marrow depletion to organ failure.
“Patients who are taking this class of anti-HIV drugs have suffered these drug toxicities for a long time,” stated Dr. Whitney Yin, assistant professor of chemistry and biochemistry.
Dosages and combinations of anti-HIV drugs can be chosen more effectively and safely. They can be used at their most effective concentrations against HIV.
However, the combination therapies using anti-HIV multi drug pills have become more successful and patients are living longer, toxicity has become more of an issue than before, she said
Pol gamma can also help to explain how mutations in pol gamma lead to various degenerative diseases, including epilepsy, encephalopathy and Alpers’ syndrome -a fatal childhood disease leading to brain and liver failure- in addition to its relevance to anti-HIV drug design.
The research on pol gamma was funded by the National Institutes of Health (NIH) and the Welch Foundation.
Anti-HIV drugs belong to different classes. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion and entry inhibitors and integrase inhibitors.
NRTIs and NNRTIs drugs target a substance called reverse transcriptase that HIV uses to infect immune system cells.There are three types of drug that work against reverse transcriptase:NRTIs: abacavir (Ziagen), AZT (zidovudine, Retrovir), ddI (didadosine, Videx), 3TC (lamivudine, Epivir), d4T (stavudine, Zerit), and FTC (emtricitabine, Emtriva) and
NNRTIs like efavirenz (Sustiva) and nevirapine (Viramune) and etravirine (Intelence).
Protease inhibitors block an enzyme in HIV. Ritonavir (Norvir), catazanavir (Reyataz)/ritonavir, darunavir (Prezista)/ritonavir, fosamprenavir (Telzir)/ritonavir, lopinavir/ritonavir (this is a combination pill called Kaletra ) and saquinavir (Invirase)/ritonavir are examples.
T-20 (enfuvirtide, Fuzeon) is one fusion inhibitor. It is given by injection.
One entry inhibitor, or CCR5 inhibitor, is also approved. It is called maraviroc (Celsentri).
All drugs can cause side-effects. The side-effects that your HIV drugs can cause should be explained to you before you start taking them. Side-effects often go away or become milder after a few weeks. Tell your doctor about side-effects, particularly rashes. If you are finding it hard to manage side-effects it is often possible to do something about them.
Most people take a combination that includes two NRTIs and either an NNRTI or a protease inhibitor.
Treatment with fusion, entry and integrase inhibitors is usually reserved for people who have taken a lot of HIV treatment in the past.