Acquired Immunodeficiency Syndrome (AIDS), resulting from Human Immunodeficiency Virus (HIV) infection, presents a substantial challenge to global public health (1). HIV depletes the immune system by targeting CD4 + T-lymphocytes, resulting in a heightened susceptibility to opportunistic infections and malignant neoplasms, ultimately advancing to AIDS, which carries a significant mortality rate (2). The Global Burden of Disease 2021 (GBD 2021) estimates that there were 40 million HIV infections globally in 2021, with women representing 55% (22.1 million), a substantially higher proportion than men (3). According to the 2023 UNAIDS report (4), women and girls constituted 53% of all people living with HIV (PLWH) and accounting for 44% of incident cases reported in 2023. Although extensive access to antiretroviral therapy (ART) has resulted in a 39.7 percent reduction in HIV-related mortality since 2010, women of childbearing age (WCBA) continue to represent a significant demographic affected, with a notably high disease burden in Sub-Saharan Africa (3, 5, 6). This region comprises roughly 81.1 percent of the worldwide infected female population and demonstrates a lifetime infection probability of 8.7 percent, significantly exceeding that of other regions (3, 5). Moreover, HIV infection in women of childbearing age presents a dual risk: it jeopardizes the health of the infected individuals and heightens the likelihood of vertical transmission from mother to child, thereby exacerbating the intergenerational effects of the disease (7, 8).

It is clear that women have heightened mucosal exposure of the genital tract, making them more vulnerable to HIV infection due to mucosal disruption during sexual intercourse (9). Moreover, immunosuppression during gestation has been shown to expedite viral replication (10). The risk of infection is further intensified by gender inequality, which hinders the ability of WCBA to negotiate protective measures in sexual conduct, particularly in Sub-Saharan Africa, where early marriages, multiple sexual partners, and sexual violence are prevalent (11, 12). The allocation of healthcare resources is globally inequitable. Although most of infected individuals receive ART, coverage is below 50 percent in areas like North Africa and the Middle East, with significant disparities in access to HIV screening and preventive treatment during pregnancy (13). Moreover, deficiencies persist in the prevention and management of mother-to-child transmission, as certain low-income nations do not ensure universal access to maternal viral load monitoring and post-exposure prophylaxis (PEP) for infants, leading to elevated rates of vertical transmission (14). The interconnected challenges of economic reliance and restricted educational achievement further hinder the ability of WCBA to access HIV prevention and care services, creating a detrimental cycle of “infection - poverty - loss of access” (15, 16). Thus, a thorough assessment of the HIV/AIDS burden among WCBA is essential to develop targeted interventions worldwide.

Despite the substantial burden of HIV/AIDS among WCBA, comprehensive assessments of its epidemiological trends and sociodemographic disparities remain scarce. A nuanced understanding of the spatiotemporal patterns of HIV/AIDS burden in this vulnerable population is critical to inform targeted interventions and advance progress toward the United Nations Sustainable Development Goals (SDGs) for maternal health. Leveraging the latest data from GBD 2021, this study systematically evaluates the global, regional, and national trajectories of HIV/AIDS among WCBA from 1990 to 2021 across four key metrics: incidence, prevalence, mortality, and disability-adjusted life years (DALYs).

The 2021 United Nations General Assembly (UNGA) Political Declaration on HIV/AIDS (32), titled “Ending Inequalities and Getting on Track to End AIDS by 2030,” outlines ambitious targets, including reducing annual new HIV infections to <370,000 and AIDS-related deaths to <250,000 by 2025 (33). Central to this framework is addressing gender disparities, particularly reducing HIV incidence among women and ensuring 95% of women access sexual and reproductive health services by 2025 to mitigate the impact of gender-based violence on HIV transmission. However, limited studies have systematically quantified the global burden of HIV/AIDS among WCBA. This study, utilizing GBD 2021 data, provides the first comprehensive estimates of HIV/AIDS incidence, prevalence, mortality, and DALYs among WCBA over 32 years (1990–2021) and projects trends to 2046. Key findings include: first, the ASIR of HIV/AIDS among WCBA exhibited a declining trend globally, while the ASPR increased; Second, there are regional differences in the burden of HIV/AIDS among WCBA, with increasing trends in high and high-middle SDI regions and decreasing trends in middle, low-middle, and low SDI areas from 1990 to 2021. As SDI increases, ASIR and ASPR trend downward in most regions. The region with the largest increase in incidence was Eastern Europe, while the region with the largest decrease was Eastern Sub-Saharan Africa. Then, HIV/AIDS among WCBA had the highest incidence in the 25–29 year age group and the highest mortality and DALYs in the 30–34 year age group. Decomposition analyses revealed that expanding population base and epidemiological characteristics are determinants of the rising burden of HIV/AIDS. Projections show a declining trend in ASIR, ASPR and ASMR to 2046.

While a previous study (34) has examined global temporal trends in the incidence of mother-to-child transmission (MTCT) of infectious diseases among WCBA, critical gaps remain. Existing research lacks in-depth analyses of the underlying drivers of high HIV/AIDS prevalence in this population. To address these limitations, this study provides a comprehensive exploration through decomposition analysis, Joinpoint regression analysis and projections. While national data are indeed vital for informing local public health decisions, GBD-derived estimates offer a valuable complementary viewpoint. They can help fill in data gaps that may exist in certain regions or for specific sub-populations, and they also enable more straightforward comparisons across different countries and regions around the world. Furthermore, we propose evidence-based policy recommendations to guide governmental and public health agencies in designing targeted interventions. The underlying causes of the elevated prevalence of HIV/AIDS among WCBA are complex, encompassing a blend of biological, social, and economic factors. Research indicates that women have a significantly higher risk of HIV acquisition after a single exposure compared to men, due to the increased surface area of the cervicovaginal mucosa and heightened cellular immune activity in the vagina (35). Moreover, age has been recognized as a crucial determinant in the risk of HIV infection. Younger women demonstrate greater susceptibility to HIV than older women, a disparity potentially attributable to the larger expanse of vulnerable genital mucosa in the immature cervix and elevated inflammation levels in the reproductive tract among younger women, both of which are positively correlated with an increased risk of HIV infection (36, 37). In numerous areas with elevated HIV prevalence, gender inequality is widespread, and women frequently encounter obstacles in sexual relationships and struggle to reject unsafe sexual practices (38). Early marriage, multiple sexual partners, and sexual violence are widespread, significantly increasing the risk of infection (6). A study indicated that women with a history of multiple sexual partners possess an approximately 1.3-fold increased likelihood of HIV infection relative to their counterparts (6, 39). The economic difficulties faced by numerous women result in the exploitation of sexual services for essential survival resources, and the prevalence of multiple concurrent sexual partners markedly heightens the risk of exposure. The estimated prevalence of HIV among women in slum areas is 13 percent (40). Furthermore, the restricted educational achievements of WCBA directly lead to inadequate health literacy and a failure to access or understand preventive information. A study in Malawi indicated that merely 12.5 percent of women were cognizant of HIV pre-exposure prophylaxis (PrEP), with awareness significantly lower among those lacking secondary education, and substantially below that of men (41).

In 2021, the incidence, prevalence, mortality, and DALY rates were highest in low SDI region. This discovery indicates an increased prevalence of HIV/AIDS in areas marked by low SDI levels. This phenomenon is chiefly ascribed to the restricted availability of medical resources and the inadequate healthcare capacity in these areas (6). This study has identified a significant upward trend in the incidence of HIV/AIDS among WCBA, with the most pronounced increases observed in high-middle SDI region. The most credible hypothesis is that high-middle SDI districts are predominantly experiencing rapid economic development, characterized by urbanization resulting in significant population migration (e.g., rural–urban mobility). These populations frequently face a deficiency in social security, a rise in transient sexual relationships, and insufficient access to sexual health services. The influence of economic growth and social development on mitigating the disease burden is obstructed by entrenched cultural contexts and the stigma linked to HIV/AIDS among WCBA (3). From 1990 to 2021, Eastern Europe experienced the most significant rise in HIV/AIDS incidence among WCBA. The principal transmission risk has transitioned from unsafe injection practices to heterosexual contact, yet access to opioid agonist therapy and needle-syringe programs remains constrained (42). Moreover, the Russo-Ukrainian war in recent years has obstructed efforts to test and treat individuals, and the ensuing economic difficulties have forced some women to participate in high-risk sex work, which is a significant concern (43). The war in Ukraine conflict has exacerbated gaps in HIV services. As a result, projections may underestimate the burden in crisis-affected areas, reinforcing the need for adaptive health systems. However, implementing these policy recommendations in real-world settings presents significant challenges, particularly in fragile or conflict-affected regions. For example, in Ukraine and Yemen, ongoing conflicts have severely disrupted healthcare infrastructure (44–46). Such disruption makes the delivery of PrEP or ART services to those in need extremely difficult. In these settings, expanding PrEP coverage or ART access requires more than just medical supplies. It also involves rebuilding healthcare facilities, training local healthcare workers, and ensuring the safe transportation of medications. Furthermore, flexible approaches such as mobile clinics and community-based distribution systems are essential for expanding PrEP coverage in these dynamic environments. Additionally, resource allocation represents a persistent challenge. While international guidelines may recommend certain high-impact interventions, local governments often lack the financial resources to implement them. This situation necessitates innovative financing mechanisms and partnerships to mobilize the required resources (3). Between 1990 and 2021, Eastern Sub-Saharan Africa experienced the most substantial reduction in incidence. This decline signifies that the notable successes of this region in decreasing HIV/AIDS incidence stem from sustained advancement. This discovery aligns with the substantial advancements achieved in the accessibility of ART, PrEP, and voluntary medical male circumcision (47–49). Nevertheless, the region remains beset by discriminatory conditions and domestic laws that not only sustain the epidemic but also exacerbate its persistence, leading to elevated prevalence rates.

Among the 204 countries or territories, Pakistan has experienced the most significant rise in HIV/AIDS incidence. The literacy rate in Pakistan is notably low, particularly among females, resulting in inadequate awareness and understanding of HIV/AIDS and its prevention (50). In WCBA, the likelihood of HIV transmission is markedly heightened by practices such as extramarital sexual relations, unsafe blood transfusions, and the utilization of contaminated syringes. Furthermore, the widespread discrimination and stigma faced by individuals with HIV/AIDS in Pakistani society has resulted in a considerable number of infected individuals choosing to hide their status (51). This has impeded efforts for early detection and treatment and may also heighten the transmission risk within the community. The government of Pakistan must implement measures to address these issues, including the provision of sex education for WCBA and the empowerment of women, to mitigate the burden of HIV/AIDS among WCBA (52). Regarding age-specific patterns, our analysis revealed that women aged 35–39 years bore the highest prevalence of HIV/AIDS, while those aged 30–34 years experienced the peak mortality and DALY burden. The natural history of HIV involves a prolonged clinical latency period. Women infected at younger ages typically progress to advanced stages after 5–10 years (53), leading to concentrated diagnosis and documented morbidity in the 35–39 age group. Furthermore, cumulative exposure risk escalates with age. Women over 30 face amplified infection risks due to extended periods of sexual activity, partner turnover, and vertical transmission exposure during pregnancy (54, 55). Critically, the peak in mortality and DALYs at 30 to 34 years is indicative of significant structural barriers in high-burden settings. Younger women often experience delayed diagnosis due to the stigma associated with HIV and the fragmentation of health services. Even after diagnosis, timely access to ART is frequently impeded by financial limitations, medication shortages, and concerns regarding side effects (3, 5). As a result, untreated infections tend to progress to severe and often fatal complications by their early thirties. We have emphasized the importance of public health interventions, such as improving the accessibility of HIV testing services, reducing the stigma associated with HIV infection, and enhancing the affordability of ART, to reduce the disease burden of HIV/AIDS among WCBA.

Joinpoint regression analysis indicated a significant decline in incidence from 1997 to 2005, coinciding with the introduction of ART in 1996 (56). A subsequent decrease in incidence was noted from 2015 to 2021. The decrease can be ascribed to the implementation of the UNAIDS fast-track strategy in 2016, which set mid-term 90–90-90 testing and treatment objectives for 2020 (33). These objectives are crucial for accomplishing the global aim of eradicating AIDS by 2030 (32). Decomposition analyses reveal that population and epidemiological changes significantly impact the burden of DALYs related to HIV/AIDS among WCBA, both globally and across SDI regions. This indicates that global population growth is directly contributing to the rise in the number of WCBA living with HIV/AIDS. The analysis indicates that epidemiological shifts, especially changes in HIV/AIDS transmission dynamics and population susceptibility, significantly contribute to the increase of DALYs. This highlights the necessity of ongoing monitoring and the modification of prevention and control strategies to tackle the global issue of HIV/AIDS. Predictive analyses indicate a slight decrease in ASPR, alongside more significant reductions in ASIR and ASMR. The significant reductions in ASIR and ASMR reflect considerable global progress in the prevention, management, and treatment of HIV/AIDS. The slight decrease in ASPR indicates the difficulties related to long-term disease management. This highlights the necessity of ongoing monitoring, enhancing prevention and control measures, and fortifying international collaboration.

In the last 30 years, the advancement of ART has significantly influenced the natural progression of HIV infection. The emergence of early diagnosis and the standardization of combination antiretroviral therapy (cART) have initiated a fundamental change in the management of HIV infection. During the 1980s, HIV infection was marked by a significant mortality rate, with an average life expectancy of merely 1–2 years post-diagnosis. The introduction of cART has converted HIV infection into a manageable chronic condition. Clinical studies indicate that 20-year-old female patients commencing ART can anticipate an increase in life expectancy of approximately 9 years (57). The global HIV epidemic persists as a serious concern, with the 2023 UNAIDS report revealing around 1.3 million new infections in 2022, and young women in Sub-Saharan Africa aged 15–24 being infected at three times the rate of their male counterparts in the same age group. This concerning epidemiological profile highlights the urgent necessity for the execution of effective preventive measures for at-risk populations, especially WCBA (4).

In the domain of HIV prevention strategies, HIV testing has become a significant secondary prevention measure, enhancing traditional behavioral interventions and condom use. The prompt diagnosis and treatment of bacterial sexually transmitted infections (STIs) have proven to significantly aid in the prevention of HIV (58). Over the past 15 years, there has been considerable advancement in biomedical prevention strategies, including the creation of PrEP and post-exposure prophylaxis (PEP) (59, 60). The utilization of PrEP has been evidenced to diminish the likelihood of HIV infection by as much as 92 percent, and long-acting injectable PrEP (e.g., cabotegravir), upon its approval in the United States in 2021, has exhibited superior results compared to oral PrEP (61). African nations have made substantial advancements in combating AIDS, evidenced by a 56 percent reduction in infections in Sub-Saharan Africa since 2010, according to the latest UNAIDS 2023 report (4). A study reveals that Sub-Saharan Africa is adopting universal testing and treatment (UTT) to diminish HIV transmission, aspiring to achieve the 90–90-90 targets set by UNAIDS (62, 63). Due to the considerable regional variability in HIV epidemiological profiles, there is an urgent necessity to enact differentiated policy reforms. HIV prevention and control strategies for WCBA should encompass multifaceted interventions, including the optimization of policy frameworks, enhancement of socio-economic empowerment, promotion of participatory community governance, and expansion of community-based rapid testing networks (64).

The global HIV prevention and control framework presently utilizes a multifaceted array of strategies, encompassing MTCT, voluntary male circumcision (VMMC), barrier methods, varied PrEP options (including oral and long-acting injectable forms), and behavioral intervention programs (65–67). The expansion and enhancement of these interventions for the key population of WCBA is a primary emphasis of national AIDS programs. The continuous enhancement of prevention and control strategies necessitates augmented financial investment and a methodical implementation approach that targets constraints such as socio-cultural factors, cognitive barriers, stigma and discrimination, and inequitable access to services. It is essential to guarantee that all individuals can accurately evaluate their infection risk and have access to testing services, both institutional and self-administered, that are devoid of financial burdens and social bias. The current treatment and prevention framework comprises three pillars (treatment, prevention, and diagnosis), yet progress toward the global objective of eradicating the AIDS epidemic can be expedited through the tailored enhancement of service models, precision, and scalability.

Nonetheless, it is crucial to acknowledge that the study possesses certain limitations. First, our analysis relied on model-derived estimates obtained from the GBD 2021 dataset rather than actual surveillance data, and there may be inherent bias between them that could affect the accuracy of the results. Secondly, as an ecological analysis, our study identifies population-level trends but cannot elucidate individual risk factors including sexual behaviors, stigma-related care barriers, and socioeconomic status. Future research linking macro-level burden with micro-level survey data is critical to inform targeted interventions. Thirdly, the lack of data from certain low- and middle-income countries may undermine the accuracy of the estimates. In low- and middle-income countries, the limited accessibility to healthcare services can hinder the ability to conduct comprehensive HIV screening and diagnosis, leading to incomplete case reporting, particularly among economically and socially disadvantaged groups. This situation may have been exacerbated by the COVID-19 pandemic (68), as health systems in these areas often have limited adaptive capacity to handle additional stress. Fourthly, the actual definition of WCBA (15–49 years) is globally inconsistent, potentially underestimating the disease burden in this group. Additionally, the utilization of static SDI categories also undermines the ability of countries to grasp how their socioeconomic evolves over time. Finally, wide UIs in settings like Equatorial Guinea reflect both data scarcity and epidemiological volatility. This suggests that we should interpret rankings from such countries with caution, given the limited surveillance infrastructure and data volatility.

HIV/AIDS among WCBA constitutes a substantial global health burden. Low SDI region, particularly in Sub-Saharan Africa, account for a disproportionate share of the global HIV/AIDS burden in WCBA, despite recent declines in incidence rates. Conversely, Eastern Europe has experienced a marked upward trend in incidence. Furthermore, the disease burden exhibits different distribution across age groups. Governments urgently need to implement context-specific interventions to address these disparities and further reduce the global burden of HIV/AIDS among WCBA across all regions.