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Research and development of anti retroviral drugs essay

Cure For more than three decades, NIAID has fostered and promoted development of antiretroviral therapies that have transformed HIV infection from an almost uniformly fatal infection into a manageable chronic condition.

In the 1980s, the average life expectancy following an AIDS diagnosis was approximately one year.

Why do animal research?

Today, with combination antiretroviral drug treatments started early in the course of HIV infection, people living with HIV can expect a near-normal lifespan.

NIAID plays a role in many stages of the antiretroviral drug discovery and development process. The search for new drugs remains a priority due to the development of resistance against existing drugs and the unwanted side effects associated with some current drugs.

NIAID supports basic research to identify novel strategies to prevent HIV from taking hold and replicating in the body, as well as preclinical research to formulate antiretroviral drugs that can be tested in people. NIAID also helps advance clinical drug development. Learn more about pediatric HIV treatment research. In addition to drug discovery, NIAID-supported research has contributed to optimizing antiretroviral therapy, reducing the number of pills needed, decreasing side effects, and determining the best drug combinations.

NIAID-supported research also has provided clear-cut scientific evidence supporting current recommendations that all people diagnosed with HIV begin treatment immediately. Read more about Starting and Staying on Antoretroviral Treatment. AZT decreased deaths and opportunistic infections, albeit with serious adverse effects.

AZT, also referred to as zidovudine, belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs. The ACTG, established in 1987, quickly began work to build on this discovery.

NIAID-supported researchers developed cell culture and biochemical test systems that allowed researchers to more easily screen drug candidates, and NIAID also played a key role in development of animal models for preclinical testing. Viral load describes the amount of HIV in the blood. These advances made it possible for researchers to use lab test results, viral load measurements in particular, to assess how well an investigational antiretroviral agent worked.

This approach requires drug trials to last roughly 6 months, whereas relying solely on clinical indicators such as progression to AIDS or death ordinarily requires trials to last years before a result is available. The Advent of Combination Therapy The limitations of single-drug treatment regimens quickly became apparent. HIV replicates swiftly and is prone to errors each time it does. These errors, or mutations, cause small changes in the virus.

HIV variants with mutations that confer resistance to an antiretroviral drug can evolve rapidly. In some people taking AZT, drug resistance developed in a matter of days. Scientists thus tested whether combining drugs would make it difficult for the virus to become resistant to all the drugs simultaneously. The trial also showed that antiretroviral therapy reduced the risk of death in people with asymptomatic, intermediate-stage disease.

CPCRA investigators found that two-drug therapy had no significant benefit over AZT alone in slowing disease progression or death in this patient group. The results of ACTG 175 and CPCRA 007, as well as other studies, indicated that prior antiretroviral experience can profoundly influence the effectiveness of some treatments, underscoring the importance of careful planning in the use of antiretroviral drugs.

Research and development of anti retroviral drugs essay major advance came in 1996, when researchers found that triple-drug therapy could durably suppress HIV replication to minimal levels, while creating a high genetic barrier against development of drug resistance. The possibility and success of triple-drug therapy, also called highly active antiretroviral therapy or HAART, was partially due to the appearance of a new antiretroviral drug class—the protease inhibitors.

In December 1995, saquinavir became the first protease inhibitor to receive FDA approval. This study found that a three-drug combination of the protease inhibitor indinavir and two NRTIs reduced the viral load to very low levels for up to one year in people who had previously been taking single-drug therapy. ACTG 320 also showed that adding at least two new drugs when switching therapy is more effective than adding single new drugs.

The side effects were burdensome, and the daily dosing was complex. Certain drugs had to be taken in combination at different intervals throughout the day, some with food and some without. The complexity made it difficult for people to adhere to the regimens long-term. Identifying New Classes of Antiretroviral Drugs To address the complexity of antiretroviral regimens, drug toxicities, and the issue of drug resistance, NIAID supports research aimed at novel formulations and development of drugs that work by different mechanisms and target various steps in the HIV replication process.

Currently, more than 30 antiretroviral drugs are available, including several fixed-dose combinations, which contain two or more medications from one or more drug classes in a single tablet.

Today, research and development of anti retroviral drugs essay people control their HIV by taking as little as one pill once a day. Access an infographic comparing antiretroviral therapy in the 1990s and today. The mid-1990s marked the emergence of another new class of antiretroviral drugs called non-nucleoside reverse transcriptase inhibitors or NNRTIs.

  1. An extensive population study the following year suggested that the epidemic had already spread globally.
  2. On learning of the outbreak, Pfizer sent in a six-member research team to the infectious disease hospital in Kano. Anna-Marie Tabor, "Recent development.
  3. In particular, no one shall be subjected, without his free consent, to medical or scientific experimentation. This makes drugs protected by patents more expensive and at the same time makes them accessible to fewer consumers than similar drugs produced in a competitive environment without patent protection in other countries.

Because they are cheaper and easier to produce than protease inhibitors, they helped scale up antiretroviral therapy in resource-limited settings. Identification of novel drug targets has played a key role in discovery and development of new antiretroviral drug classes.

Research and development of anti retroviral drugs essay

For example, since the 1980s, scientists have known that a molecule called CD4 is the primary receptor for HIV on immune system cells. This discovery inspired researchers to look other co-receptors. This work laid the foundation for the development of the CCR5-blocking drug maraviroc, which received FDA approval in 2007. Another major antiretroviral drug class emerged in 2007, with FDA approval of the integrase inhibitor raltegravir.

Raltegravir quickly became a valued component for combination antiretroviral therapy, but HIV can follow several pathways to develop resistance to the drug. HIV variants resistant to raltegravir may also be resistant to elvitegravir, another first-generation integrase inhibitor.

Dolutegravir, which received FDA approval in 2013, is a second-generation integrase inhibitor that appears to have a high barrier to development of HIV drug resistance. In clinical trials, dolutegravir was effective both for people living with HIV who had not previously taken HIV therapy and for people who were treatment-experienced, including those for whom first-generation integrase inhibitors were ineffective.

Antiretroviral Drug Discovery and Development

Additional advantages of dolutegravir include convenient once-daily dosing, a good safety profile, and a relatively low production cost.

Dolutegravir now is included in two of the first-line regimens that the U. Department of Health and Human Services medical practice guidelines recommend for adults with HIV, and it was recently added to World Health Organization guidelines as an alternative first-line agent for adults.

Experts consider it likely that dolutegravir will be used globally with increasing frequency in the future. NIAID continues to support work to develop new antiretroviral drugs and new tools to improve HIV treatment, such as long-acting therapies that may serve as alternatives to daily antiretroviral therapy.