PHWR Public Health Weekly Report

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), once regarded as a fatal infectious disease, has now become a chronic condition that can be effectively managed and prevented through advances in treatment and innovations in prevention strategies [1-3]. On a global scale, the steady decline in annual new HIV infections can be attributed to the advancement and dissemination of antiretroviral therapies (ARTs) and prevention efforts. New infections, which numbered approximately 2.2 million cases per year in 2010, have decreased by approximately 40% to approximately 1.3 million cases by 2024 [4]. However, Republic of Korea (ROK) continues to exhibit a stagnant trend with approximately 1,000 new infections annually, with the proportion of foreign nationals among infected individuals increasing from 19.4% in 2020 to 25.5% in 2023 [5]. This domestic scenario highlights the urgent need to strengthen HIV management strategies that prioritize prevention efforts. With a particular focus on prevention strategies using ARTs, this manuscript aims to provide a comprehensive review of the emergence of the Treatment as Prevention (TasP) and Undetectable=Untransmittable (U=U) concepts; the introduction and history of pre-exposure prophylaxis (PrEP); current status and policies regarding PrEP on a global and domestic scale; and the latest trends in PrEP, including long-acting PrEP formulations (cabotegravir and lenacapavir), followed by a discussion of future prospects.

1. HIV Transmission Status and the Importance of Prevention Strategies

The global HIV epidemic has surpassed its zenith and exhibited a declining trend owing to the strides made in the domains of prevention and treatment. New infections, which reached a peak of 3.4 million cases annually in 1996, have declined by 61% to approximately 1.3 million cases in 2024, marking a historic low [4]. Meanwhile, ROK has maintained an annual infection rate of roughly 1,000 cases since the mid-2010s, exhibiting no substantial decrease. In 2023, the number of new HIV infections was 1,005, marking a slight decrease compared to the previous year but indicating no significant change. Among these, 89.9% of HIV-positive individuals were men, and the 20s and 30s age groups accounted for 64%. Furthermore, foreign nationals accounted for 256 new infections, constituting 25.5% of the total, with their proportion steadily increasing over the past few years [5]. These domestic epidemiological patterns suggest the need to strengthen HIV prevention efforts, highlighting the importance of proactive testing, early treatment, and the expansion of prevention services for vulnerable populations. In fact, the Korea Disease Control and Prevention Agency (KDCA) has established its second comprehensive countermeasure plan with the objective of reducing new domestic infections by 50% by 2030 compared to 2023 [6] and is currently promoting a policy shift toward prevention. Thus, there has been growing attention to novel approaches that combine treatment and prevention, which are expected to play a pivotal role in curbing the domestic HIV epidemic.

2. Concepts of TasP and U=U

The success of HIV prevention hinges on early diagnosis and linkage to care [7,8]. Recently, the widespread adoption of HIV self-testing has lowered the barriers to testing for high-risk groups by ensuring anonymity and improving accessibility [9]. The importance of early diagnosis and linkage to care lies in the scientific evidence showing that suppression of HIV through prompt treatment can effectively prevent its transmission [10,11]. TasP is the concept that HIV-positive individuals with the virus suppressed to undetectable levels through ART do not transmit it to others [12-15]. This concept gained scientific evidence through the results of the large-scale clinical study HPTN 052 in 2011 [12]. The HPTN 052 study garnered global attention by demonstrating that HIV-positive individuals who started ART early achieved at least a 96% reduction in the transmission risk to their HIV-negative partners. This landmark study was the first to demonstrate the preventive effect of treatment, showing that early diagnosis and active treatment of HIV-positive individuals is essential not only for individual health but also for public health.

Following the success of HPTN 052, the PARTNER study (involving heterosexual and male homosexual couples) disclosed a notable finding that not a single instance of HIV transmission was observed when HIV-positive individuals on treatment with fully suppressed viral loads engaged in unprotected sexual intercourse with their partners [13,14]. Combining the findings of PARTNER 1 and PARTNER 2, it has been concluded that the risk of HIV transmission “scientifically approaches zero” when an HIV-positive partner has an undetectable viral load, with no transmission observed even after approximately 130,000 instances of condomless sexual intercourse. These findings were consolidated into the message of “U=U,” which posits that if HIV is undetectable, it cannot be transmitted. Since 2016, health authorities and experts worldwide have officially endorsed the U=U campaign [16]. The establishment of U=U has the potential to reduce the social stigma surrounding HIV-positive individuals, thereby motivating them to actively participate in treatment. This, in turn, can increase treatment rates, prevent secondary transmission, and create a virtuous cycle [17]. This integrated strategy of treatment and prevention has now become the most crucial pillar of the global HIV/AIDS response [18]. However, the reality is that the U=U concept has not yet been fully established in Korean clinical settings. Despite the scientific reality of U=U, the stigma and discrimination surrounding HIV can lead to problems such as test avoidance and delayed treatment. Therefore, continuous promotion of the message of U=U is required in healthcare settings, and policies must ensure trust through institutional protections (e.g., the prohibition of discrimination in employment and insurance).

3. Emergence and Global Adoption of PrEP

PrEP is a strategy in which individuals with a high risk of HIV infection receive ART in advance to prevent infection. The concept of PrEP was demonstrated to be feasible through animal studies and small-scale clinical trials [19-21], and its efficacy in humans was first proven by the large-scale iPrEx clinical trial published in 2010 [22]. iPrEx was a study comparing a daily oral Truvada (tenofovir/emtricitabine) regimen with a placebo group among approximately 2,500 homosexual men and transgender women from six countries, including the United States and Brazil. Consequently, the overall risk of HIV infection was reduced by 44% in the PrEP treatment group. Notably, the preventive effect was 73% among participants who reported a medication adherence of ≥90%; additionally, it reached 92% among participants whose drug concentrations were objectively confirmed to be present in their bodies, thereby providing an objective confirmation of medication adherence. iPrEx provided a compelling demonstration of the proof-of-concept for PrEP, as it was the first to show that HIV infection could be prevented with a single daily dose in high-risk populations.

In 2011–2012, studies such as Partners PrEP and TDF2, which evaluated the prevention of heterosexual transmission, demonstrated the efficacy of PrEP in both men and women [23,24]. Partners PrEP, which examined HIV-positive couples in Africa, demonstrated that PrEP use by the HIV-negative partner reduced the risk of infection by approximately 75%, supporting the preventive efficacy of PrEP in the context of heterosexual transmission. In light of the accumulated evidence, the United States Food and Drug Administration (FDA) formally sanctioned the use of Truvada in 2012, marking its designation as the world's first approved PrEP therapy. Subsequently, in 2015, the World Health Organization also recommended PrEP use for all high-risk populations. Since then, the PROUD study in the UK and IPERGAY study in France (2014–2015) have further demonstrated the realistic preventive efficacy of PrEP (over 86% risk reduction), highlighting the potential of on-demand PrEP in clinical settings, thus significantly enhancing confidence in the effectiveness of PrEP [25,26].

Among oral PrEP options, Descovy (tenofovir alafenamide/emtricitabine) was introduced after the demonstration of noninferior preventive efficacy in comparison to Truvada and safety advantages regarding renal and bone metabolism in men who have sex with men (MSM) and transgender women in a large-scale randomized trial (DISCOVER) in 2019 [27]. However, the indication for women and other demographic groups remains constrained due to an absence of substantial data regarding the prevention of infection through vaginal intercourse. The prevailing protocol entails once-daily therapy, with the caveat that on-demand therapy is not advised. From a clinical perspective, the medication is indicated for use in individuals with an estimated glomerular filtration rate of at least 30 ml/min (≥60 ml/min is generally recommended for Truvada). Potential metabolic changes, such as elevated lipid levels and weight gain, should be closely monitored. Finally, Descovy is a viable alternative oral PrEP option for high-risk groups who have concerns about renal or bone toxicity or for whom Truvada use is difficult. However, it is not currently approved for the purpose of PrEP use in ROK.

As such, the accumulation of substantial evidence has led to a global escalation in the adoption of PrEP. In 2023 alone, over 3.5 million individuals utilized PrEP on at least one occasion, with cumulative initiations reaching approximately 6.2 million by the end of the year. Moreover, by the end of 2024, a total of 160 countries had integrated PrEP recommendations into their respective national guidelines [28]. The United States Centers for Disease Control and Prevention established a target in its 2019 “Ending the HIV Epidemic” strategy to augment PrEP accessibility, to ensure that over 50% of the population requiring PrEP receives it by the year 2025 [29]. In the Asia-Pacific region, countries such as Australia, Thailand, Vietnam, and Taiwan have proactively implemented PrEP. Taiwan has reported that the introduction of PrEP can significantly contribute to reducing new HIV infections [30]. Thus, PrEP has become a central pillar of global HIV prevention, and, in conjunction with condoms, safe injection practices, and TasP, forms a crucial component of a comprehensive prevention strategy [31].

4. Current Status and Policy Changes of PrEP in the ROK

In ROK, it is observed that the interest in introducing PrEP has grown, leading to the publication of domestic guidelines for HIV pre-exposure prophylaxis in 2017, spearheaded by the Korean Society for AIDS, recommending PrEP for high-risk groups such as MSM, bisexual men, and transgender women [32]. Subsequently, in 2018, Truvada received approval for PrEP use in ROK; additionally, in 2019, the country expanded health insurance coverage for PrEP medications to include HIV-negative partners of individuals living with HIV. Nevertheless, in spite of the preliminary implementation, the utilization of domestic PrEP remained restricted owing to cost burdens and a lack of awareness. For HIV-positive individuals receiving effective ART, the risk of transmission is negligible, meaning that their HIV-negative partners face a low actual risk of infection (U=U). Conversely, MSM constitute a high-risk group for HIV infection. However, their access to treatment has been constrained by financial burdens stemming from the challenges in obtaining national health insurance coverage. In reality, the monthly cost of HIV PrEP medications is approximately KRW 400,000, excluding insurance coverage. The restricted scope of insurance coverage may impede access to these medications for high-risk groups due to financial constraints.

In order to enhance this situation and transition towards a prevention-centered HIV management framework, the KDCA has incorporated the PrEP activation project as a core task within the “Second Acquired Immunodeficiency Syndrome Prevention and Management Plan (2024–2028)” [6]. The “PrEP Support Pilot Program” was initiated in 2024 as a concrete implementation of this strategy. The initial implementation of this program occurred in select regions, including Seoul and Busan, during the months of November and December 2024. Thereafter, it underwent nationwide expansion, encompassing all 17 metropolitan cities and provinces, commencing in 2025. This government-led PrEP support program is intended to increase the access of vulnerable populations at risk of HIV infection to PrEP, thereby reducing new infections. High-risk groups participating in support programs (e.g., HIV-negative individuals with HIV-positive partners, MSM and sexual minorities, high-risk occupational groups, etc.) are eligible for substantial government assistance covering a significant portion of their medical and medication costs. Specifically, the provisions encompass full coverage of out-of-pocket expenses for mandatory tests before PrEP prescription (such as HIV antigen/antibody tests), and for the state to cover the remaining costs of PrEP medication, with individuals paying only a fixed monthly copayment of KRW 60,000 per person. The goal is to significantly reduce economic barriers and promote PrEP utilization.

The support program targets individuals seeking PrEP prescriptions in departments such as infectious diseases, with approximately 110 healthcare institutions nationwide participating in the program as of 2025. Those wishing to participate can check the designated healthcare facilities for PrEP in each region through the information sites operated by the Korea Federation for HIV/AIDS Prevention, such as iSHAP, to find and receive treatment. The KDCA plans to examine the data accumulated through support programs to establish institutional foundations, such as expanding insurance coverage for PrEP, with the expectation that this will result in a reduction in the number of new infections annually.

5. Latest Trends in PrEP: Long-acting Preventive Medications

Current PrEP is primarily administered in the form of a once-daily oral pill, most commonly Truvada. However, the rapid development of long-acting formulations is ushering in a new era of "tailored prevention." Of particular interest is the potential for injectable PrEP to enhance medication adherence. The leading examples are cabotegravir long-acting (LA) and lenacapavir LA.

1) Cabotegravir

Cabotegravir, an integrase inhibitor, is an injectable PrEP administered once every 2 months [33]. In the large-scale clinical trials HPTN 083 (targeting MSM and transgender women) and HPTN 084 (targeting women), cabotegravir demonstrated significantly higher preventive efficacy compared to daily oral PrEP [34,35]. The results of HPTN 083 demonstrated a 66% reduction in the incidence of HIV infection in the cabotegravir injection group in comparison with the oral group (13 vs. 39 infections). In HPTN 084, the injection group demonstrated an 89% reduction in the infection rate compared to the oral group (4 vs. 34 infections), thus proving greater preventive efficacy than that of existing oral PrEP. These results indicate that the bimonthly injectable PrEP could be a highly effective alternative for individuals who encounter difficulties with the regular ingestion of pills. Nevertheless, given the nature of the drug, a long-term follow-up is necessary to monitor the residual effects and potential tolerance associated with the long-acting injection. Furthermore, the issues of pharmaceutical pricing and accessibility must be given due consideration before domestic introduction. Cabotegravir received approval from the FDA in late 2021 and is being utilized as the world's first long-acting PrEP. The implementation of PrEP has commenced in certain nations, with an ongoing discourse centering on the augmentation of accessibility through the diversification of PrEP alternatives in the long term.

2) Lenacapavir

Lenacapavir, a capsid protein inhibitor, is a novel mechanism-of-action drug that has been developed to target and inhibit multiple stages of the HIV life cycle, thereby acting as an effective anti-HIV agent [36]. Developed as an ultra-long-acting PrEP administered via subcutaneous injection once every 6 months, it maintains preventive efficacy with just two injections per year. Lenacapavir has been designated as the “Breakthrough of the Year 2024” by the international journal Science, which has lauded its innovation and clinical achievements. The preventive efficacy of lenacapavir has been demonstrated in highly encouraging results in recent clinical studies. In a clinical trial involving women, the drug demonstrated a 100% prevention rate (zero infections in the lenacapavir group) [37]. Studies involving MSM and transgender women also confirmed a 99.9% seronegative retention rate [38]. In light of these remarkable findings, the FDA formally sanctioned the use of lenacapavir for the PrEP indication in June 2025. In Europe, following an accelerated review, approval was granted in August 2025, thereby confirming its introduction. Lenacapavir provides the benefit of an extended dosing interval, thereby significantly enhancing convenience. It is anticipated that the utilization of this technology will be effective even in populations with low medication adherence or limited access to healthcare. However, as with cabotegravir, long-acting injections necessitate continuous monitoring for residual effects and development of resistance. Pricing and accessibility are also factors that must be considered for domestic introduction. A clinical trial is currently underway for the once-a-year intramuscular injection regimen, with encouraging results confirmed in Phase 1 [39]. If subsequent clinical trials prove successful and the drug becomes available for actual use, it is expected to maximize convenience to an even greater extent than that of the current regimen of subcutaneous injections administered once every 6 months. The PrEP options that are currently approved and primarily utilized are summarized in Table 1.

Table 1 Summary of PrEP options

Option	Dosing	Advantage	Consideration
Oral Truvada (TDF/FTC)	Once daily or on-demand	Cost-effective Extensive clinical evidence	Adherence issue Renal/bone adverse effects
Oral Descovy (TAF/FTC)	Once daily	Favorable renal/bone safety	Cost
Cabotegravir long-acting	IM every 2 months	High efficacy Improves adherence by reducing pill burden	Long “tail” with resistance risk Visit adherence
Lenacapavir long-acting	SC every 6 months	High efficacy Longest dosing interval	Access and cost

PrEP=pre-exposure prophylaxis; TDF=tenofovir disoproxil fumarate; FTC=emtricitabine; TAF=tenofovir alafenamide; IM=intramuscular; SC=subcutaneous..

Furthermore, there is ongoing research on prophylactic vaginal rings, such as the Dapivirine vaginal ring, which is effective for a duration of 1 month [40,41]. Additionally, research is being conducted on the prevention of HIV using broadly neutralizing antibodies [42,43], and on the development of the ultimate HIV vaccine [44,45]. However, the most advanced candidates for practical implementation to date are the aforementioned long-acting antiretroviral PrEPs, which are expected to significantly transform the landscape of PrEP in the near future. The advent of lenacapavir signifies a paradigm shift in the approach to HIV prevention, transitioning from the era of daily pill intake to a semiannual injection regimen. The implementation of these customized prevention strategies is anticipated to substantially contribute to the reduction of new infections by addressing the diverse needs of high-risk groups and enhancing participation in prevention programs.

The field of HIV/AIDS prevention has undergone a fundamental shift over the past decade. The paradigm shift towards TasP and emergence of the U=U movement have profoundly influenced the perceptions and treatment strategies for individuals living with HIV. These shifts have led to the establishment of a novel public health model that emphasizes “early diagnosis, early treatment, and prevention of transmission.” Moreover, the advent of PrEP underscores the efficacy of self-administered prophylactic medication in preventing HIV infection among high-risk populations, thereby contributing to a substantial global reduction in new HIV infections. In alignment with this global movement, ROK has been undertaking measures to augment its prevention-oriented policies. While the number of new HIV infections in the country has not yet decreased significantly, the country is reaching a turning point due to the nationwide expansion of PrEP support programs and strengthening of testing infrastructure. Specifically, the government's PrEP support program, initiated in 2025, has eliminated economic barriers, thereby enabling more vulnerable populations to access preventive benefits. This development suggests the possibility of a future downward trend in new domestic infections.

The future of HIV prevention will be defined by the comprehensive integration of diverse instruments and methodologies. A combination prevention strategy is needed, integrating fundamental condom utilization and safe injection practices with early testing and treatment, along with the judicious administration of oral PrEP and long-acting PrEP. Concurrently, social initiatives such as enhancing access to healthcare services, promoting prevention strategies, addressing stigma, and encouraging testing should be undertaken. Concomitant with the domestic introduction of long-acting preventative treatments, there is an imperative for research and development to persist in the pursuit of more convenient and safer prophylactic treatments. Moreover, it is critical to prioritize the development of an HIV vaccine, which should be regarded as the ultimate objective in this field.

The global target date of 2030 for ending the HIV/AIDS epidemic is approaching. Decades of global efforts in the prevention and treatment of HIV/AIDS have resulted in significant progress, as evidenced by a decline in new HIV infections and deaths due to AIDS in some regions. ROK should also usher in an era of prevention, building upon these scientific advances and policy support. By proactively integrating innovative approaches that disrupt the conventional distinctions between treatment and prevention, it is possible to effectively manage the domestic HIV/AIDS epidemic and make substantial progress towards the 2030 AIDS elimination goal.

Ethics Statement: Not applicable.

Funding Source: None.

Acknowledgments: None.

Conflict of Interest: The author has no conflicts of interest to declare.