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.
