Abstract:
The multidrug-resistant (MDR) human immunodeficiency virus 1 (HIV-1) infection is an
unmet medical need. HIV-1 capsid plays an important role at different stages of the HIV-1 replication
cycle and is an attractive drug target for developing therapies against MDR HIV-1 infection. Lenacapavir
(LEN) is the first-in-class HIV-1 capsid inhibitor approved by the USFDA, EMA, and Health
Canada for treating MDR HIV-1 infection. This article highlights the development, pharmaceutical
aspects, clinical studies, patent literature, and future directions on LEN-based therapies. The literature
for this review was collected from PubMed, authentic websites (USFDA, EMA, Health Canada,
Gilead, and NIH), and the free patent database (Espacenet, USPTO, and Patent scope). LEN has
been developed by Gilead and is marketed as Sunlenca (tablet and subcutaneous injection). The
long-acting and patient-compliant LEN demonstrated a low level of drug-related mutations, is active
against MDR HIV-1 infection, and does not reveal cross-resistance to other anti-HIV drugs. LEN
is also an excellent drug for patients having difficult or limited access to healthcare facilities. The
literature has established additive/synergistic effects of combining LEN with rilpivirine, cabotegravir,
islatravir, bictegravir, and tenofovir. HIV-1 infection may be accompanied by opportunistic infections
such as tuberculosis (TB). The associated diseases make HIV treatment complex and warrant drug
interaction studies (drug–drug, drug–food, and drug–disease interaction). Many inventions on
different aspects of LEN have been claimed in patent literature. However, there is a great scope for
developing more inventions related to the drug combination of LEN with anti-HIV/anti-TB drugs in
a single dosage form, new formulations, and methods of treating HIV and TB co-infection. Additional
research may provide more LEN-based treatments with favorable pharmacokinetic parameters for
MDR HIV-1 infections and associated opportunistic infections such as TB.
