Journal of the International AIDS Society最新文献

The number of new HIV acquisitions globally has declined, but not rapidly enough to meet the 2030 targets set by UNAIDS and the United Nations Sustainable Development Goals (SDGs) [1, 2]. Despite intense efforts such as those to support the UNAIDS 95-95-95 targets and to expand the availability of oral pre-exposure prophylaxis (PrEP), progress in primary prevention of HIV acquisition has lagged. There were 1.3 million new HIV acquisitions in 2022, and at current rates of decline, this number is projected to decrease to 900,000 new HIV acquisitions by 2030, which is far from the SDG target of 300,000. The number of people living with HIV will continue to increase from 39 million in 2022 to a projected 45 million in 2030 [1-3].

In this Viewpoint, we review the potential of HIV broadly neutralizing monoclonal antibodies (bnAbs) as a long-acting injectable immunoprophylaxis regimen to reduce HIV acquisition in high-risk populations. HIV bnAbs can recognize and neutralize a wide range of HIV strains, making them a promising tool for HIV prevention [4]. In the last 10−15 years, several HIV bnAbs have been isolated and have entered clinical development [5] (Table 1). These include antibodies against the CD4 binding site, the V3 glycan supersite and the V2 apex of the Env trimer. During the COVID-19 pandemic, monoclonal antibodies were delivered on an unprecedented scale for the prevention of SARS-CoV-2, showing the feasibility of using antibodies for prevention.

The proof-of-concept that an HIV bnAb can prevent HIV acquisition was demonstrated in 2021 by the Antibody Mediated Prevention (AMP) trials [6]. These two harmonized phase 2B clinical trials—one conducted in the United States and Latin America in men who have sex with men and transgender persons and the other conducted in sub-Saharan Africa in cisgender women—showed that the prototype HIV bnAb VRC01 could prevent HIV acquisition, but was only effective against sensitive virus (IC80 < 1 µg/ml). The determinant of efficacy was the susceptibility of the infecting HIV strain to the antibody. The trials also provided a target serum antibody titre as a correlate of protection [7]. For HIV bnAbs to achieve broad protection against circulating HIV strains, a combination of antibodies targeting multiple epitopes will be needed. Several groups have shown that a cocktail of three complementary bnAbs, such as a combination of antibodies targeting the CD4 binding site, V3 loop and V2 loop, provide broad neutralization coverage of global viruses in vitro, which supports the rationale for clinical evaluation of such bnAb cocktails [8, 9].

Next-generation HIV bnAbs have entered clinical trials [5, 10] (Table 1). These antibodies have been engineered to include mutations in the variable Fab region for greater potency and breadth, as well as mutations M428L/N434S or “LS” in the constant

The International Day against Homophobia and Transphobia annually memorializes the rights violations of transgender people, yet once a year will not be enough to remember the atrocities that transgender people have to face and endure every single day. Globally, perspectives on transphobia are shaped by cultural, legal and social contexts. In multiple countries, there is a growing recognition of transgender rights, with laws evolving to protect against discrimination and hate crimes [1]. However, transphobia remains pervasive, affecting access to healthcare, education, employment and social acceptance [2].

In the Asia-Pacific region, transgender people often face severe social stigma, legal penalties, and even violence, with little to no legal protection [3]. In some instances, colonial legacies have left enduring impacts on societal views towards gender diversity, further entrenching transphobia [4]. Transgender communities in the Philippines and Thailand have been historically struggling to battle for equality. In the Philippines, the “Equality Law” was first introduced in 2007, which is an anti-discrimination bill based on sexual orientation, gender identity, gender expression and sex characteristics (SOGIESC). Due to the ongoing failure to pass the law, it has since been repeatedly refiled. In Thailand, the “Gender Equality Act” was enacted by the national government in 2015, which broadly promoted gender equality. In addition, Thailand recently passed a same-sex marriage bill that the lower house of the Parliament approved by an overwhelming majority [5].

Although some Asian countries, like India, recognize transgender people as a separate gender for legal documents, many others do not, reflecting the institutionalized transphobia persisting across the region. This leaves individuals vulnerable to pervasive stigma and discrimination [6], fuelled by entrenched fears of identity falsification and deeply ingrained transphobic attitudes rooted in hetero-cis-normative beliefs [7]. Negative media representations further exacerbate these challenges, often linking transgender identities with stereotypical depictions of sex work and violence [8].

Notably, only 23 out of 193 United Nations member states legislated legal gender recognition based on self-identification [9]. Without legal gender recognition in many countries in Asia and the Pacific, transgender people find it challenging to access public services and healthcare, due to transphobic environments. This can include client intake forms with binary gender options, judgemental attitudes from healthcare providers and a lack of transgender-competent care services [10]. In the Philippines, the transgender community faces difficulties in accessing medical services in the country. Gender-affirming hormone therapy and surgery can only be accessed by tho