30 years of HIV therapy: Current and future antiviral drug targets

Significant advances in treatment have turned HIV-1 into a manageable chronic condition. This has been achieved due to highly active antiretroviral therapy (HAART), involving a combination regimen of medications, including drugs that target Reverse Transcriptase, Protease, Integrase, and viral entry, explored in this review. This paper also highlights novel therapies, such as Lenacapavir, and avenues toward functional cure targeting the CCR5 co-receptor, including the Δ32 mutation. Challenges of HAART include lifelong adherence, toxicity, drug interactions, and drug resistance. Future therapeutic strategies may focus on underexplored antiviral targets. HIV-1 Tat and Rev proteins have essential HIV-1 regulatory functions of transcriptional elongation of the viral long terminal repeat and nuclear export of intron-containing HIV-1 RNA, respectively. These non-enzymatic proteins should thus be investigated to identify small molecules that inhibit HIV-1 replication, without causing undue toxicity. Continued innovation is essential to address therapeutic gaps and bring us closer to a potential HIV-1 cure.