Food and Drug Administration for the treatment of HIV

Nathan Smith^*
*Correspondence: Nathan Smith, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, NE, USA, Email:

Keywords

AIDS • Antiretroviral therapy • FDA approval

Introduction

Since the early days of the HIV/AIDS epidemic, tremendous strides have been made in understanding the virus, its transmission and the development of effective treatments. Among the most significant breakthroughs is the development of antiretroviral therapy, a cornerstone in the management of HIV infection. ART has revolutionized the lives of individuals living with HIV, extending life expectancy, improving quality of life and reducing the risk of transmission. In this article, we will delve into the evolution of ART, its mechanisms of action, current guidelines for its use, challenges and its role in the global response to HIV. The first reported cases of what would later be identified as HIV/AIDS emerged in the early 1980s, triggering a worldwide public health crisis. During the early years of the epidemic, no specific treatment was available and the disease was associated with a rapid and devastating decline in health. The first breakthrough came with the approval of zidovudine in 1987, making it the first drug approved by the U.S. Food and Drug Administration for the treatment of HIV. AZT, a nucleoside reverse transcriptase inhibitor, marked the beginning of HIV treatment. NRTIs were the first class of drugs used to combat HIV. They work by interfering with the virus's ability to replicate its genetic material, specifically by inhibiting reverse transcriptase, an enzyme crucial for viral replication. HIV is an RNA virus and to replicate, it must convert its RNA genome into DNA. Reverse transcription is the process by which the virus's RNA is transcribed into DNA [1].

Literature Review

After reverse transcription, the viral DNA is integrated into the host cell's genome, allowing the virus to establish a persistent infection. The integrated viral DNA can then be transcribed and translated by the host cell machinery, producing new virus particles that can infect other cells. NRTIs act by mimicking the building blocks of DNA, but they lack a critical component that prevents the formation of a complete DNA chain. As a result, the viral reverse transcriptase mistakenly incorporates NRTIs into the growing viral DNA chain, effectively terminating viral replication. However, this class of drugs has limitations, including the development of drug resistance and side effects. While NRTIs represented a significant step forward in the treatment of HIV, the virus quickly developed resistance to single-drug regimens. Researchers recognized that a combination of drugs with different mechanisms of action could be more effective in controlling HIV and reducing the likelihood of resistance. This realization led to the development of highly active antiretroviral therapy in the mid-1990s. HAART typically combines two NRTIs with a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. PIs work by blocking the action of the protease enzyme, preventing the maturation of new virus particles. NNRTIs, on the other hand, directly inhibit the reverse transcriptase enzyme but do so through a different mechanism than NRTIs [2].

Discussion

The introduction of HAART represented a turning point in the battle against HIV. Patients who previously faced a grim prognosis could now experience viral suppression and immune system recovery. The "AIDS cocktail," as it was often called, was a game-changer in HIV treatment, offering new hope to those living with the virus. Over the years, the landscape of antiretroviral therapy has continued to evolve. Today, ART regimens are more streamlined, more potent and generally have fewer side effects compared to early treatments. These regimens are tailored to the individual's needs, taking into consideration factors such as the stage of infection, resistance patterns and potential side effects. NRTIs, such as tenofovir, emtricitabine and abacavir, are a key component of many ART regimens. NNRTIs like efavirenz and rilpivirine inhibit the reverse transcriptase enzyme by binding to it and disrupting its activity. PIs, including lopinavir and atazanavir, block the protease enzyme, preventing the production of mature virus particles. INSTIs, such as dolutegravir and raltegravir, target the integrase enzyme, which is responsible for inserting the viral DNA into the host cell genome. These drugs, like maraviroc and enfuvirtide, prevent HIV from entering and fusing with host cells. Ritonavir and cobicistat are often used as "boosters" to increase the effectiveness of other antiretroviral drugs in the bloodstream [3].

However, maintaining viral suppression is not always straightforward, as several factors can affect the effectiveness of ART. Consistent adherence to ART is essential. Missing doses or stopping treatment can lead to viral rebound and the development of drug resistance. Some medications, including over-the-counter drugs and supplements, can interact with antiretroviral drugs, affecting their efficacy. Over time, the virus can mutate and develop resistance to certain antiretroviral drugs. Resistance testing helps guide treatment decisions. Antiretroviral drugs can cause side effects that may lead to treatment interruptions or switches to alternative medications. While ART has transformed the management of HIV, it is not without challenges and limitations. Maintaining strict adherence to ART can be difficult for some individuals due to various factors, including pill burden, side effects, stigma and psychosocial issues. Adherence support and patient education are crucial [4].

The emergence of drug-resistant HIV strains poses a threat to the effectiveness of ART. Resistance testing is essential to guide treatment decisions. While modern ART regimens are generally well-tolerated, some individuals may experience side effects. It's important for healthcare providers to work with patients to manage side effects and explore alternative treatments when necessary. The availability and affordability of ART can vary widely around the world. Ensuring access to treatment for all who need it remains a significant challenge. Stigma associated with HIV can hinder individuals from seeking and adhering to treatment. Addressing HIV-related stigma is essential to improving care outcomes. Long-term use of ART may be associated with certain health concerns, such as cardiovascular and metabolic issues. Regular monitoring and comprehensive care are critical. As the population of individuals aging with HIV grows, there is a need for research and care strategies tailored to the unique challenges and comorbidities of this population [5].

Beyond its primary role in the treatment of HIV, ART has proven to be a powerful tool in HIV prevention. TasP involves providing ART to individuals living with HIV to suppress the virus and reduce the risk of transmission. As mentioned earlier, achieving and maintaining an undetectable viral load significantly reduces the risk of HIV transmission to sexual partners. PrEP is a preventive approach in which individuals who are at high risk of HIV infection take a daily combination of antiretroviral drugs. PrEP has been shown to be highly effective in reducing the risk of HIV acquisition. Both TasP and PrEP are crucial components of the global effort to reduce new HIV infections. These strategies complement other prevention measures, such as condom use, harm reduction and education. The introduction of antiretroviral therapy has had a profound impact on the global HIV epidemic. While significant challenges remain, particularly in low- and middle-income countries, ART has contributed to several positive outcomes. ART has significantly reduced AIDS-related mortality, allowing individuals living with HIV to lead longer and healthier lives. Combined with prevention efforts, ART has contributed to a decrease in the number of new HIV infections in many regions [6].

Conclusion

Antiretroviral therapy has fundamentally transformed the landscape of HIV treatment and prevention. From the early days of the epidemic to the present, ART has evolved into highly effective and well-tolerated regimens that allow individuals living with HIV to lead long and healthy lives. Moreover, ART's role in reducing the risk of HIV transmission has expanded its impact to prevention efforts. While significant challenges persist, including drug resistance, treatment access and stigma, the progress made in the field of HIV therapy is a testament to the power of science, innovation and global collaboration. The ongoing commitment to research, treatment optimization and the elimination of disparities in HIV care is vital as we continue our journey toward an AIDS-free world.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Moore, Gary L., Rodger W. Stringham, David S. Teager and Tai-Yuen Yue. "Practical Synthesis of the Bicyclic Darunavir Side Chain:(3 R, 3a S, 6a R)-Hexahydrofuro [2, 3-b] furan-3-ol from Monopotassium Isocitrate."Org Process Res Dev21 (2017): 98-106.

   Google Scholar, Crossref, Indexed at

2. Cauchon, Nina S., Shirley Oghamian, Soraya Hassanpour and Michael Abernathy. "Innovation in chemistry, manufacturing and controls—a regulatory perspective from industry."J Pharm Sci 108 (2019): 2207-2237.

   Google Scholar, Crossref, Indexed at

3. Gnanadhas, Divya Prakash, Prasanta K. Dash, Brady Sillman and Aditya N. Bade, et al. "Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs."J Clin Investig127 (2017): 857-873.

   Google Scholar, Crossref, Indexed at

4. Rautio, Jarkko, Nicholas A. Meanwell, Li Di and Michael J. Hageman. "The expanding role of prodrugs in contemporary drug design and development."Nat Rev Drug Discov 17 (2018): 559-587.

   Google Scholar, Crossref, Indexed at

5. Soni, Dhruvkumar, Aditya N. Bade, Nagsen Gautam and Jonathan Herskovitz, et al. "Synthesis of a long acting nanoformulated emtricitabine ProTide."Biomater 222 (2019): 119441.

   Google Scholar, Crossref, Indexed at

6. Sillman, Brady, Aditya N. Bade, Prasanta K. Dash and Biju Bhargavan, et al. "Creation of a long-acting nanoformulated dolutegravir."Nat Commun 9 (2018): 443.

   Google Scholar, Crossref, Indexed at