Current and Promising Multiclass Drug Regimens and Long-Acting Formulation Drugs in HIV Therapy

In HIV-1 therapies, dual-drug and triple-drug combinations of antiretroviral therapy (ART) have radically improved the prognosis of HIV-1 infected people. The clinical usage of drug combinations has established high efficacy with constant viral load repression, saving T cells, and low adverse drug reactions compared to mono drug therapy treatment and thus has drawn intensive attention from researchers and pharmaceutical enterprises for HIV treatment and prevention. The switching of antiretroviral regimens from one combination to another is relatively easier for patients experiencing adverse effects or drug toxicities or requesting modification or simplification of their regimen. In addition, the choice of the combination regimen reduces viral resistance drastically when compared to the mono drug regimen. Several two-and three-drug complete regimens like Delstrigo, Complera, Stribild, Dovato, Juluca, etc., were approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection in adults and children. Multiclass combination drug regimens, which include varied classes of antiretroviral agents that work by interrupting the two or more enzymes required for the life cycle of HIV replication, have proved effective in the treatment of HIV infections, resulting in the approval of novel combination regimens for antiretroviral therapy. For complete virologic inhibition, antiretroviral combination regimens should include at least two or preferably three active drugs from two or more classes of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs or NtRTIs), Protease inhibitors (PIs), and Integrase Strand Transfer Inhibitors (INSTIs). At present, several researchers are focused on developing newer, long-acting formulations of different classes of mono-and dual antiretroviral drugs. Recently, the first and only complete long-acting regimen of extended-release injectable suspension of cabotegravir and rilpivirine by intramuscular gluteal was approved once monthly for HIV treatment by the FDA. Several antiretroviral drugs are under investigation in preclinical and clinical studies through various formulations, such as implants, injectables, intravenous, and subcutaneous. This book chapter aims to summarize the currently available multiple drug combinations information and the development of long-acting antiretroviral drugs for HIV treatment and prevention in the last two decades.

Keywords: AIDS, Antiretroviral therapy, HIV, Long-acting therapy, Three-drug combination therapy, Two-drug combination therapy.