Acquired Immunodeficiency Syndrome

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, the multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for the discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body's health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from patients' bodies. A potential strategy called "lock-in and apoptosis" targets the budding phase of the life cycle of the virus and leads to susceptibility to apoptosis of HIV-1 infected cells for the elimination of HIV-1 reservoirs and, ultimately, for complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA)-approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

BackgroundThe HIV epidemic continues to grow fastest among men who have sex with men (MSM) in Malaysia in the presence of stigma and discrimination. Engaging MSM on the internet using chatbots supported through artificial intelligence (AI) can potentially help HIV prevention efforts. We previously identified the benefits, limitations, and preferred features of HIV prevention AI chatbots and developed an AI chatbot prototype that is now tested for feasibility and acceptability.ObjectiveThis study aims to test the feasibility and acceptability of an AI chatbot in promoting the uptake of HIV testing and pre-exposure prophylaxis (PrEP) in MSM.MethodsWe conducted beta testing with 14 MSM from February to April 2022 using Zoom (Zoom Video Communications, Inc). Beta testing involved 3 steps: a 45-minute human-chatbot interaction using the think-aloud method, a 35-minute semistructured interview, and a 10-minute web-based survey. The first 2 steps were recorded, transcribed verbatim, and analyzed using the Unified Theory of Acceptance and Use of Technology. Emerging themes from the qualitative data were mapped on the 4 domains of the Unified Theory of Acceptance and Use of Technology: performance expectancy, effort expectancy, facilitating conditions, and social influence.ResultsMost participants (13/14, 93%) perceived the chatbot to be useful because it provided comprehensive information on HIV testing and PrEP (performance expectancy). All participants indicated that the chatbot was easy to use because of its simple, straightforward design and quick, friendly responses (effort expectancy). Moreover, 93% (13/14) of the participants rated the overall chatbot quality as high, and all participants perceived the chatbot as a helpful tool and would refer it to others. Approximately 79% (11/14) of the participants agreed they would continue using the chatbot. They suggested adding a local language (ie, Bahasa Malaysia) to customize the chatbot to the Malaysian context (facilitating condition) and suggested that the chatbot should also incorporate more information on mental health, HIV risk assessment, and consequences of HIV. In terms of social influence, all participants perceived the chatbot as helpful in avoiding stigma-inducing interactions and thus could increase the frequency of HIV testing and PrEP uptake among MSM.ConclusionsThe current AI chatbot is feasible and acceptable to promote the uptake of HIV testing and PrEP. To ensure the successful implementation and dissemination of AI chatbots in Malaysia, they should be customized to communicate in Bahasa Malaysia and upgraded to provide other HIV-related information to improve usability, such as mental health support, risk assessment for sexually transmitted infections, AIDS treatment, and the consequences of contracting HIV.

Combination antiretroviral therapy (cART) has significantly improved the prognosis of individuals living with human immunodeficiency virus (HIV). Acquired immunodeficiency syndrome has transformed from a fatal disease to a treatable chronic infection. Currently, effective and safe anti-HIV drugs are available. Although cART can reduce viral production in the body of the patient to below the detection limit, it cannot eliminate the HIV provirus integrated into the host cell genome; hence, the virus will be produced again after cART discontinuation. Therefore, research into a cure (or remission) for HIV has been widely conducted. In this review, we focus on drug development targeting cells latently infected with HIV and assess the progress including our current studies, particularly in terms of the "Shock and Kill", and "Block and Lock" strategies.

IntroductionThe global HIV response, once a model of progress and innovation, faces a profound moment. Despite four decades of pivotal scientific and programmatic advances-most notably in antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP)-the world remains off track to meet the 2025 and 2030 targets for ending AIDS as a public health threat. New acquisitions and AIDS-related deaths remain unacceptably high, particularly among key populations and in low- and middle-income countries. The abrupt U.S. funding reversals in 2025 have severely disrupted support for HIV efforts. Cuts to U.S. and international institutions have compromised HIV prevention, treatment and surveillance systems worldwide, and may already have begun reversing two decades of progress.DiscussionTo avert this crisis, the HIV and public health community, together with governments and global funders, must urgently invest in scaling long-acting treatment and prevention tools, rebuild disaggregated data systems and strengthen implementation science rooted in community-led approaches. Digital health technologies offer promise to enhance service delivery, surveillance, monitoring and evaluation, especially in resource-constrained settings, but demand ethical governance and infrastructure investment. The global research ecosystem must become more evenly distributed and inclusive, with a shift towards country-led partnerships, national data sovereignty and regional co-operation.ConclusionsLooking to 2030 and beyond, the strategy to end HIV should include expanded access to long-acting ART and PrEP, sustained investments in HIV vaccine and cure research, and robust monitoring and evaluation systems. Achieving epidemic control-and ultimately ending the HIV pandemic-will require not only biomedical tools but also political will, community leadership and equitable financing. The lessons of the past underscore that sustained progress is possible, but only if we meet this moment with urgency, imagination and solidarity.