LAUSR

HIV has accounted formore than 35million deaths globally since the HIV/AIDS epidemic began in 1981. According to the latest UNAIDS figures, at the end of 2017, an estimated 36·9 million people were living with HIV. Most of the infected population is dependent on life-saving combination antiretroviral therapy (cART) that suppresses HIV replication, prevents the development of AIDS, and reduces the risk of transmission. However, cART is not a cure, and providing lifelong daily treatment to all infected individuals is no easy feat to achieve. Daily treatment can be challenging and lead to adherence interruption, thus resulting in a rebound of the virus and potential progression to AIDS. Moreover, one in ten individuals receiving cART have been reported to experience adverse effects due to several factors, such as complex drug-to-drug interactions, underlying comorbidities, and drug toxicities arising from concomitant medication use. In a bid to overcome challenges of daily adherence to cART, development of a long acting antiretroviral injection (combining cabotegravir and rilpivirine) that offers once-monthly administration was reported in two independent 48-week trials (NCT02951052 and NCT02938520) on March 7, 2019, at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, WA, USA. Early data from these trials suggested promising results in viral control with the monthly regimen and participant satisfaction in over 85% cases compared to taking daily dose cART. Notwithstanding the remarkable efficacy of cART, the so-called latent reservoir of HIV represents the main barrier to HIV cure. HIV is thought to establish latency by infecting primarily the long-lived CD4 + T cells and by integrating into the host's genomic DNA. Once established, HIV latency can shut off viral transcription in infected cells, allowing the provirus to remain undetected by the host immune system, and can hinder effective treatment by antiretroviralmedication. A latent reservoir of HIV can persist for the host's lifetime. The main research focus in identifying a cure for HIV has been directed at defining and eliminating the viral reservoir. The so-called “kick and kill” (alternatively referred to as “shock and kill”) approach was developed to remove the entire reservoir by forcing viral replication of the latent virus with latency-reversing agents and subsequently eliminating the infected cell population via antiviral immunity or cytopathic effects. This scheme focuses on identifyingways to adopt thehost antiviral immunity to ensure complete eradication of reactivated virions. This idea has led to several key developments, including antiHIV vaccination, HIV-specific broadly neutralising antibodies, and transfusion of anti-HIV natural killer cells. The main limitations that have prevented this advance from being realised are the challenges of inducing expression from the entire HIV latent reservoir and ensuring