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In the early 1980s when the epidemic began, AIDS patients were not likely to live longer than a few years. With the development of safe and effective drugs, however, people infected with HIV now have longer and healthier lives. DRUGS FOR HIV INFECTION Currently, the drugs approved by the Food and Drug Administration to treat HIV infection fall into three major classes. Reverse transcriptase (RT) inhibitors These inhibitors interfere
with the reverse transcriptase which converts HIV RNA to HIV DNA. There are two main types of RT
inhibitors: nucleoside/nucleotide and non-nucleoside. The non-nucleoside RT
inhibitor works by
interfering with the enzyme's catalytic ability. The nucleoside/nucleotide RT
inhibitors are analogues of the natural deoxynucleotides needed to synthesize the viral DNA.
Their deoxyribose lacks a 3'-hydroxyl group,
which is required to form the 5'-3' phosphodiester bond
in a DNA chain. Therefore, after a nucleoside/nucleotide RT
inhibitor is incorporated into the growing HIV DNA chain during the reverse
transcription process, the DNA chain cannot be extended further. Without a
complete DNA, HIV replication is blocked.
Protease inhibitors These inhibitors interfere with the protease that HIV uses to cleave precursor proteins (gag, pol and env), making functional proteins. The protease inhibitor works by blocking the enzyme's active center.
Fusion inhibitors These inhibitors interfere with the virus' ability to fuse with the cellular membrane, thereby blocking entry into the host cell. They work by binding to the fusion protein gp41.
Drugs Approved for HIV Infection
* Pediatric approval No Cure For Hiv/Aids Currently available drugs do not cure HIV infection or AIDS. They can suppress the virus, even to undetectable levels, but are unable to completely eliminate HIV from the body. Hence, infected patients still need to take antiretroviral drugs. Highly Active Antiretroviral Therapy (HAART) Counters Drug Resistance As HIV reproduces itself, different strains of the virus emerge, some that are resistant to antiretroviral drugs. Therefore, doctors recommend patients infected with HIV take a combination of antiretroviral drugs known as HAART. This strategy, which typically combines drugs from at least two different classes of antiretroviral drugs, has been shown to effectively suppress the virus when used properly. Developed by NIAID-supported researchers, HAART has revolutionalized how we treat people infected with HIV by successfully suppressing the virus and decreasing the rate of opportunistic infections. Antiretroviral Drug Effects On Opportunistic Infections And Aids-Associated Co-Infections People infected with HIV have impaired immune systems that can leave them susceptible to opportunistic infections (OIs) and AIDS-associated co-infections, caused by a wide range of microorganisms such as protozoa, viruses, fungi, and bacteria. One example is hepatitis C virus (HCV) infection which can lead to liver cancer. Potent HIV therapies such as HAART, however, have produced dramatic responses in patients by suppressing HIV and slowing the progression of OIs and AIDS-associated co-infections. These therapies allow the immune system to recover, sustain, and protect the body from other infections. Hence, antiretroviral drugs provide a way for the immune system to remain intact and effective, thereby improve the quality and duration of life for people with HIV. Side Effects As Barriers To Antiretroviral Drug Use People taking antiretroviral drugs often have low adherence to complicated drug regimens. The current recommended regimen involves taking several antiretroviral drugs each day from at least two different classes, some of which may require fasting and cause unpleasant side effects such as nausea and vomiting. In addition, antiretroviral drugs may cause more serious medical problems, including metabolic changes such as abnormal fat distribution, abnormal lipid and glucose metabolism, and bone loss. Therefore, NIAID is investigating simpler, less toxic, and more effective drug regimens. NEW DRUGS IN THE PIPELINE The Pharmaceutical Research and Manufacturers Association of America maintains a database of new drugs in development to treat HIV infection. They include new protease inhibitors and more potent, less toxic RT inhibitors, as well as other drugs that interfere with entirely different steps in the virus' lifecycle. These new categories of drugs include
In addition, scientists are learning how immune modulators help boost the
immune response to the virus and may make the existing anti-HIV drugs more
effective. Therapeutic vaccines
Reference: National Institute of Allergy and Infectious Diseases, USA.
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