Antiretrovirals and HIV

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Introduction

HIV is a major global public health issue, claiming 36.3 million [27.2–47.8 million] lives with no cure for HIV infection. However, with increasing access to effective HIV prevention, diagnosis, treatment, and care, including opportunistic infections, HIV infection has become a manageable chronic health condition, enabling people living with HIV to lead long and healthy lives.

There were 37.7 million [30.2 million–45.1 million] people globally living with HIV in 2020. As of 30 June 2021, 28.2 million people were accessing antiretroviral therapy, up from 7.8 million [6.9 million–7.9 million] in 2010.

Goals of antiretroviral therapy

HIV produces new copies of itself inside an infected cell, which can then infect other healthy cells within the body. The more cells HIV infects, the greater its impact on the immune system (immunodeficiency). Antiretroviral medicines slow down replication by interfering with its replication process in different ways and, thus, the spread of the virus within the body.

The key goals of antiretroviral therapy are to:

• to prevent HIV from multiplying
• achieve and maintain suppression of plasma viremia to below the current assays’ level of detection;
• improve overall immune function as demonstrated by increases in CD4+ T cell count;
• prolong survival;
• reduce HIV associated morbidity;
• improve overall quality of life; and
• reduce risk of transmission of HIV to others

It is important to remember that current antiretroviral regimens do not eradicate HIV; viral rebound occurs rapidly after treatment discontinuation, followed by CD4 decline, with potential for disease progression. It is essential to strictly follow the prescribed regimen to avoid viral rebound and the potential for selection of drug resistance mutation. A combination regimen should consist of preferably 3 (but at least 2) active agents based on genotype resistance test results.

Antiretroviral drugs

There are six classes of drugs used in antiretroviral therapy:

• nucleoside reverse transcriptase inhibitors (NRTI): They compete with natural deoxynucleotides for incorporation into a growing viral DNA chain. However, NRTIs lack a 3'-hydroxyl group on the deoxyribose moiety. This difference results in incorporating an NRTI, and the next incoming deoxynucleotide cannot form the following 5', 3' phosphodiester bond needed to extend the DNA chain. The result is a chain termination in DNA synthesis. Names of FDA approved drugs: Abacavir, emtricitabine, lamivudine; Tenofovir disoproxil fumarate, zidovudine
• non-nucleoside reverse transcriptase inhibitor (NNRTI): They block reverse transcriptase (RT) by directly binding to the enzyme. Though NNRTIs do not get incorporated into the viral DNA, they inhibit the movement of protein domains of RT that are essential to carry out the DNA synthesis. Name of FDA approved drugs-Efavirenz, etravirine, nevirapine, rilpivirine
• protease inhibitor (PI): Bind HIV-1 protease and block proteolytic cleavage of protein precursors necessary for the production of viral particles. Name of FDA approved drugs: Atazanavir, darunavir, fosamprenavir, ritonavir, saquinavir, tipranavir
• integrase inhibitor (II): Block the action of integrase, preventing the viral genome from inserting itself into the DNA of a host cell. Name of FDA approved drugs

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