The trend analysis of HIV and other sexually transmitted infections among the elderly aged 50 to 69 years from 1990 to 2030

Background The HIV and other sexually transmitted infections (STI) excluding HIV among the elderly population urgently require more attention and in-depth study. We aimed to present and predict the worldwide of its burden from 1990 to 2030 using data from the Global Burden of Disease (GBD) study. Methods Leveraging the 2019 GBD study, we investigated the average annual percentage change (AAPC) of HIV and other STI in incidence, prevalence, disability-adjusted life years (DALYs), and mortality rates for individuals aged 50–69 across different age groups, genders, sociodemographic index (SDI) regions, and nations. The incidence of STI in the population from 2020 to 2030 was explored by Bayesian age-period-cohort (BAPC) prediction model. Results The HIV incidence rate experienced its fastest growth 1990–1992, peaked in 1996, and gradually declined thereafter, with the 2019 rate being lower than that of 1990. The prevalence rate didn't present a sharp turning point. After 2006, its growth rate accelerated. Both DALYs and mortality rates plateaued high between 2002 and 2005, followed by a decline. The decline was steepest from 2005–2012, yet the rate of decrease slowed noticeably from 2012–2019.When segmented by age, HIV was more prevalent among those aged 55–59 and 50–54, with the 50–54 age group witnessing the fastest decline in incidence rates. However, the fastest growth in prevalence rates was seen among the 60–64 and 65–69 age groups. The other STI incidence rate declined from 1990–1996, increased up to 2006, declined until 2015, and then saw a resurgence with accelerated growth thereafter. The prevalence rate showcased varied trends, with a notable increase in the past five years. The highest growth in incidence rate was among the 65–69 age group. We predict that the incidence rate of STI will increase in the future. Conclusions Overall, despite the evident decline in incidence, mortality rates, and DALYs, the prevalence of HIV and other STI among the elderly is rising, and both demonstrated significant trend variations across different ages, genders, SDI regions, and nations. Comprehensive sexual health education, clinical care and adjustments in health service strategies based on the evolving trends of HIV and other STI among the elderly are paramount.

eight to 16%, approximately 5.7 million older adults with HIV, with a significant 80% of them living in less wealthy nations.It is projected that this will increase to 21% [4].Due to the success and expansion of antiretroviral therapy (ART) programmes [5,6], the lifespan of older individuals with HIV is extending, making it increasingly crucial to understand their quality of life.A UK study indicated that between 2014 and 2019, 92.5% of newly diagnosed cases of sexually transmitted infections (STI) were in those under 45.Yet, while younger age groups saw a decrease in new STI diagnoses, there was a noticeable increase among those aged 45 to 64 [7].While previous studies have examined the incidence and rate of change in STI among adolescents and young adults aged 10-24 in 204 nations from 1990 to 2019 [8], our focus shifts to those aged 50-69.Although this older demographic isn't the primary group affected by STI, numerous studies indicate a rising trend in their incidence and prevalence rates [9].Furthermore, with improvements in medical care, younger infected individuals are aging, amplifying the global burden of STI in older populations.Therefore, using the Global Burden of Disease (GBD) database, we aim to investigate the average annual percent change (AAPC) in incidence, prevalence, disability-adjusted life years (DALYs), and mortality rates among older individuals aged 50-69 across different age groups, genders, SDI regions, and nations.This study intends to explore the development and trends of STI in older adults and to identify vulnerabilities in the global transmission of STI in order to provide data to improve the quality of life of older patients with STI, to transform prevention and care strategies for older patients, and to reduce the global burden of STI.

Data source
For the GBD 2019, we retrieved data from the Global Health Data Exchange that spanned multiple time points (Global Burden of Disease 2019 Collaborative Network.Seattle, United States: Institute for Health Metrics and Evaluation, 2020.Available from https://vizhub.healthdata.org/gbd-results/).This data encompassed information from 1990 to 2019, covering 369 diseases and injuries across 204 regions, including HIV and other sexually transmitted infections excluding HIV (other STI, 'chlamydial infection', 'genital herpes', 'gonococcal infection', 'syphilis' and 'trichomoniasis') [10], based on the World Health Organization's 10th revision of the International Classification of Diseases.In 2019, the data from these diseases combined represented over 95% of the global DALYs burden due to STI.Sources of data for STI consisted of literature reviews, public health department disclosures, pre-pregnancy clinic reports, data from GBD partners, and case studies.All these data sets are accessible through the GBD 2019's tools on VizHub at healthdata.org [10,11].

Study population and data collection
Initially, we selected our area of study on the website to be 'HIV' and 'Sexually transmitted infections excluding HIV'.Subsequently, we downloaded the corresponding data segregated by age, gender, sociodemographic index (SDI) region, geographical area, and nation.Our target population was individuals aged 50-69.Based on the GBD's definitions and the requirements of our study, we categorised age groups as 50-54, 55-59, 60-64, and 65-69 years.Both genders were considered.The SDI is the geometric mean of the total fertility rate for individuals under 25, the average educational duration for those 15 and older, and the lag-distributed income per capita, scaled between 0 to 1.It acts as a comprehensive metric reflecting the socioeconomic conditions affecting health outcomes in each region [10].An SDI value of 0 represents the lowest income, least education, and highest fertility rate.The SDI is divided into five quintiles: low, low-middle, middle, high-middle, and high [11].Our study also aligned with the GBD's definition, considering 21 regions with similar geography and epidemiological characteristics, as well as 204 individual nations and territories.We extracted annual data from 1990 to 2019, encompassing the number and rates of incidence, prevalence, death and DALYs.DALYs is a measure used in public health to capture the total amount of healthy life lost to all causes.DALYs essentially combine years of life lost due to premature mortality and years lived with disability.In GBD 2019, estimates with uncertainty intervals (UI) were generated for all locations in every year, even in instances of sparse or missing data [10].All reported rates were standardised, expressed per 100 000 individuals, ensuring comparability.Within the GBD framework, a specific algorithm was employed to estimate the uncertainty of a health statistic by iterating the estimation 1000 times.These 1000 estimates were arranged in ascending order.We selected the 25th and 975th values from these iterations to represent the 95% uncertainty interval (UI) [8].

Statistical analysis
By fitting the data on a logarithmic scale, the software optimally connects multiple distinct segments using the points where a monotonic trend shows significant changes in its trajectory.These points are termed 'joinpoints' and each joinpoint was tested using the Monte Carlo permutation method.When choosing the model in joinpoint software, we combined the Weighted Bayesian Information Criterion approach with judgment of researchers.Joinpoint regression analysis is widely acknowledged as a vital tool for identifying shifts in trends, accurately determining points of trend changes, and assessing their significance [12,13].This provides valuable insights into the dynamic changes in the epidemiology of diseases.As a result, we employed joinpoint regression analysis to calculate the Annual Average Percentage Change (AAPC).The AAPC provides an integrated measure of the trend over a particular period, representing a weighted average of the Annual Percentage Change (APC) via regression analysis.The numeric value of AAPC indicates the percentage change per year (increase, decrease, or stable).For instance, an AAPC of 0.1 suggests a 0.1% growth in the rate every year.The trend of incidence rates was delineated using the AAPC value and its 95% confidence interval (CI).Calculations for AAPC were done for the periods 1990-1999, 2000-2009, 2010-2019, and the entire span from 1990 to 2019.Bayesian age-period-cohort (BAPC) model (details available elsewhere [14]) was applied to predict the prevalence rate from 2020 to 2030 for female and male by R packages 'BAPC' and 'INLA'.The BAPC model has been proven to have higher accuracy in predicting the disease burden, so we used it within an integrated nested Laplacian approximation to project the prevalence rate from 2020 to 2030 [15].All statistical analyses were executed using R Studio software (version 4.3.1)and the Joinpoint Regression Program (version 5.0.2).In our study, both the listed 'number' and 'rate' were accompanied by UI values enclosed in parentheses.All rates are presented per 100 000 population.Alongside the AAPC, CI values are also provided within brackets.The raw data obtained from GBD download and some analysed data are presented in the Tables S1-10 in the Online Supplementary Document.

Global analysis
The HIV incidence rate among elder-aged individuals increased from 1990 to 1999 (AAPC 1.74, 0.09 to 3.42), but consistently declined from 2000 to 2019 (Table 1).Overall, the HIV incidence rate in 2019 (12.7 per 100 000 population (9.4 to 16.2); AAPC −2.2 (−2.6 to -1.9)) (Table S1 in the Online Supplementary Document) was lower than the incidence in 1990 (19.7 per 100 000 population (15.6 to 24.4)).As for prevalence rate, an overall upward trend was also observed from 1990 − 2019, and the growth rate was most accelerated during 1990 − 1999.The DALYs and mortality rates generally declined over 1990-2019.The joinpoint regression analysis identified a substantial change in incidence of HIV in 1992HIV in , 1996HIV in , 2005HIV in , 2018, and especially in 1992 and 1996 (Figure 1, panel A, Table S2 in the Online Supplementary Document).Prevalence rate exhibited a more linear progression, with an accelerated growth rate post-2006 (Figure 1, panel B).Both DALYs and mortality rates presented a high plateau phase, peaking around 2002 and 2005, and then declining (Figure 1, panels C-D).The decline from 2005-2012 was the most accelerated, but the pace slowed between 2012-2019, unfortunately not returning to the levels observed in 1990.
The incidence rate trend for other STI from 1990-2019 stands in contrast to that of HIV, predominantly showing an upward trajectory (AAPC 0.2 (0.05 to 0.17)) (

Analysis by age group
Subsequently, we stratified the global elderly population by age.Across all four age groups, there was a pronounced decline in the HIV incidence rate (  2).In terms of HIV prevalence rate, there was a general uptrend (Table 3).The most rapid rise was observed in the 60-64 years age group, reaching an AAPC    3).
It's noteworthy that trichomoniasis exhibited the highest other STI incidence rate across all age groups, while genital herpes led in prevalence, followed closely by trichomoniasis.In 2019, the incidence and prevalence rates for trichomoniasis, syphilis, gonococcal infections, genital herpes, and chlamydial infections were all highest among those aged 50-54 years (Table S1 in the Online Supplementary Document).

Analysis by gender group
When breaking down by gender, disparities become apparent.Both genders saw a significant decline in HIV incidence rates, while the other STI excluding HIV displayed a minor increase: for female, the AAPC was −2.S4 in the Online Supplementary Document), the most rapid growth in incidence rate was observed for trichomoniasis (AAPC 0.21 (0.16 to 0.25)), while chlamydial infections led in prevalence growth (AAPC 0.19 (0.12 to 0.26)).For male, chlamydial infections took the lead for both incidence (AAPC 0.14 (0.04 to 0.23)) and prevalence growth (AAPC 0.12 (0.02 to 0.21)).

Analysis by SDI regions
When segmenting by the sociodemographic index (SDI) regions, a discernible pattern emerges for HIV incidence (Table S5 in the Online Supplementary Document).Generally, the lower the SDI, the higher the incidence rate (Figure 4 S10 in the Online Supplementary Document).The prevalence rate of HIV in both genders has increased, with an average increase of 63.97% for female, from 505.93 in 2019 to 829.59 in 2030.Male increased from 556.59 to 710.85, an increase of 27.72%.In terms of the other STI, female increased from 30 770.01 to 31 165.98, while male increased from 18 920.04 to 19 019.91.Overall, the prevalence of STI in the population from 2020 to 2030 showed an increasing trend, with the exception of HIV prevalence increasing more significantly compared to other STI, and the increase in female was greater than that in male.

DISCUSSION
Our findings revealed that in 2019, the incidence and prevalence numbers for the 50-69 age bracket constituted 8.77 and 19.91% of global HIV cases and 11.72 and 26.74% of global other STI, respectively.Previous studies have also indicated a gradual rise in the incidence and prevalence of STI among the elderly worldwide [2,3,9,16], such as South Africa [17,18], the US [19,20], the UK [7,21], China [22,23], Canada [24], Australia [9], and Spain [25].Similar to the global trend [26], we have found that sub-Saharan Africa is also the epicenter for HIV.According to our data, nations such as Lesotho, Equatorial Guinea, Mozambique, Eswatini, and Botswana are among the hardest hit.Additionally, countries including Cuba, Kazakhstan, Hungary, the Philippines, Iran, and Norway have experienced the fastest growth in the health burden of STI.These countries require our focused attention because they are vulnerable to the impact of epidemics when unprepared for increased pressure on resources.These findings also indicate that HIV infection rates and health burdens among elderly populations vary significantly across different regions, potentially influenced by factors such as regional culture, social structures, and health care resource allocation.As a result, it is crucial to develop targeted intervention measures and allocate health care resources for their health protection.
On a broad scale, our study indicated that worldwide efforts have led to a decrease in HIV incidence among individuals aged 50-69, culminating in 2019's incidence rates being lower than those in 1990.The rise in HIV incidence rates was most rapid between 1990 and 1992, after the peak in 1996, a gradual decline ensued.Coincidentally, antiretroviral therapy (ART) first became available, around the same time around the same time, in 1996 [27].As a result, this decline may be attributed to the widespread use of ART globally in the nearly two decades.The prevalence rates didn't demonstrate a stark shift and post-2006, the growth rate of prevalence quickened -a surprising trend.This can be substantiated by widespread application of ART, societal emphasis on HIV prevention and the fact that since 2003, funding for HIV prevention and control by the US Centers for Disease Control and Prevention has steadily increased.Following a plateau between 2002 and 2005, DALYs and mortality rates due to HIV witnessed a marked decline.Perhaps, a reduction in mortality rates and subsequent increase in life expectancy are causes for the upward linear trend in the prevalence rates for the 50-69 age group -a trend incongruent with incidence rates.Overall, in contrast to declining HIV incidence rates from 1990 to 2019, other STI rates rose over the same period [28].This may can be interpreted that although the funding from the US Centers for Disease Control and Prevention for the prevention and control of other STI has not changed since 2003, there has been a significant reduction in the funding, when adjusted for inflation.
Our research indicates that the number of HIV incidences is highest among population aged 50-54, the young elderly population, but its rate of incidence decreases most rapidly.This suggests that HIV prevention efforts may be most effective among this age segment, and continuing to intensify prevention and control measures targeting this age group could yield the greatest benefits for the overall elderly population.Regrettably, irrespective of the age group, the DALYs and mortality rates in 2019 were nearly double those of 1990.Gender-wise, women generally exhibit lower incidence and prevalence rates of HIV compared to men, with a slightly more rapid decline in their rates of incidence, which aligns with the global distribution [29].However, a consistent body of literature also highlights that women continue to face disproportionately higher risks of HIV infection and associated mortality due to factors such as social discrimination, lack of support, and comorbidities [26].Consequently, the efforts in its prevention and control among the elderly female population must persist with sustained attention and resources to ensure that their health and well-being are not overlooked.Delineating by age, the highest other STI incidence rate was seen in the 50-54 age bracket, whereas the fastest growth rate was among those aged 65-69.This pattern echoes the HIV trend, emphasising the need to monitor other STI prevalence among older individuals.Overall, efforts should be concentrated on enhancing the prevention of other STI among the elderly population aged 50-54 and 65-69, particularly targeting male seniors.Additionally, special attention should be given to addressing the incidence of chlamydia and the prognosis of genital herpes among male elderly individuals, along with tackling the prevalence and prognosis issues of trichomoniasis among female seniors.
In our correlation analysis, prevention and control strategies for STI should vary according to SDI levels.In middle SDI regions, both youth [30] and the elderly face heightened risks, necessitating comprehensive plans, increased investment, expanded medical services, and reinforced prevention measures to address the rapidly growing disease burden.High SDI regions should prioritise basic prevention and control measures, such as enhancing sex education, promoting social support and awareness of sexually transmitted diseases, and providing broader testing services to prevent the rise in incidence rates.Low SDI regions, despite declining HIV rates, still face substantial risks, underscoring the need for continued development of health facilities, universal medical services, and community education efforts to curb disease spread.
The rising trends of STI in the elderly can be attributed to several factors.First and foremost, due to the widespread adoption of systematic therapies, mortality rates have seen a decline.The extensive use of Highly ART has lowered the mortality rates of patients with HIV, consequently extending their life expectancy [20].Second, societal progression in terms of perspectives, coupled with the sexual activeness of the elderly, stands in stark contrast to their often outdated views on sexual health.The societal shifts over the past decades have made it more common for older individuals to meet new partners and engage with sex workers.However, older generations are less likely to have received formal sex education in schools and are typically excluded from sexual health promotion campaigns [7].Such factors might lead them towards unsafe sexual practices, heightening the risk of STI transmission [31].Contrary to the misconception that elderly individuals are sexually inactive, literature consistently indicates that sexual activity among those over 50 is higher than assumed [17,[32][33][34][35].However, global overviews on HIV and aging show that very little is known about the HIV knowledge and sexual behaviours of older adults worldwide [36,37].Older individuals are less likely to use condoms, increasing their risk of contracting or transmitting HIV [17].The widespread use of sildenafil (commonly known as Viagra) enables older men to engage in sexual activity more frequently [38].Moreover, older men who use Viagra are more likely to partake in unprotected intercourse [39].Third, the allocation of sexual health resources for the elderly is inequitable, particularly in the realms of health education and clinical care.Healthcare professionals are often hesitant to broach the topic of sexual health with older patients.Due to feelings of embarrassment or other societal barriers, seniors are typically reticent to raise sexual health concerns with their health care providers.Moreover, compared to younger individuals, the elderly tend to exhibit a more extended lag between recognising symptoms and seeking clinical intervention [40].In a sample of individuals aged 40-80 in the USA over the years, more than 75% of those with sexual health issues did not seek the counsel of health experts [41].Such delays pose significant challenges in the effective prevention and management of STI within this demographic.Until now, global responses to HIV have predominantly focused on mothers, children, adolescent girls, and young women, often overlooking the unique needs of older individuals living with HIV [30].The burden of STI in the elderly is increasingly concerning [7,42].Older individuals with STI are confronting emerging challenges, such as heightened risks for cardiovascular diseases, chronic kidney ailments, and osteoporosis [43][44][45][46].Beyond these amplified medical needs, many elderly individuals with STI also grapple with mental health and psychosocial issues like substance use, feelings of isolation, and a lack of social support [47][48][49].
In this context, we have also endeavoured to forecast the incidence rate of STI for the decade spanning from 2020 to 2030.This is similar to previous predictions for individual regions [7,50].Our projections are only grounded in the age brackets and gender disparities observed in the year 2019, coupled with the World Health Organization's estimates of the forthcoming global populace, with the projected rates mirroring the global STI landscape as it was in 2019.Should there be an enhancement in global health status and economic conditions, our analysis, which is contingent upon the SDI, suggests that the actual STI incidence rate could witness a substantial decline compared to our forecasts.Furthermore, an upscale in global governmental investments dedicated to STI prevention and treatment, along with a marked improvement in the sexual health awareness among the elderly demographic, could potentially lead to a reduction in the estimated incidence rates [51][52][53].We believe that these insights underscore the potential for significant progress in the fight against STI, provided that strategic investments and public health initiatives are optimised and intensified on a global scale [9,[54][55][56].The pandemic of COVID-19 has interestingly impacted the incidence rates of STI.Due to the containment measures implemented during the pandemic [57], there was a decline in the incidence of STI in many regions [58][59][60].However, there has been a recent rebound in these rates, which calls for further analysis.
Strengths of our study include, first and foremost, our pioneering use of the GBD database to analyse the annual changes in incidence, prevalence, DALYs, and mortality rates of HIV and other STI for the 50-69 age group from 1990 to 2019.Additionally, we utilised joinpoint regression analysis, providing a comprehensive fit for HIV and other STI trends from 1990 to 2019, offering a clear and intuitive depiction of their trajectories.Moreover, by employing the joinpoint model, we calculated the AAPC for various subgroups, which directly reflects their rate of change.However, there are limitations to our study.First, our study relies on the GBD database.Given the diverse data sources across nations and regions within the GBD, there's a considerable margin of error.Furthermore, considering the potential stigma elderly individuals might associate with STI, we estimate that the data obtained might underrepresent the actual situation.Second, perhaps the most crucial limitation to highlight is that our analysis only delved into a few straightforward influencing factors.However, there are numerous elements impacting the incidence and prevalence of STI, such as economic burdens, health care policies, and more.Merely examining the correlation of rates over the years doesn't offer a holistic and comprehensive understanding of the global trends.This aspect certainly warrants more in-depth exploration in future study endeavours.In future research, exploring alternative data sources or methodologies to validate and supplement GBD data could enhance the accuracy and reliability of the data.Addressing potential data acquisition barriers stemming from underlying societal biases could involve utilising more privacy-protective data collection methods, such as anonymous surveys or community participatory research, to mitigate patient reporting biases and more accurately reflect real-world situations.Additionally, further expanding the scope of analysis to investigate other factors influencing STI incidence and prevalence, such as economic burdens and health care policies, represents a promising direction for future research.

Figure 1 .
Figure 1.Joinpoint regression analysis of global HIV incidence (Panel A), prevalence (Panel B), DALYs (Panel C), and mortality (Panel D) in the elderly aged 50-65 years from 1990 to 2019.The joinpoints have been labeled in the figure, and the corresponding APC and P-values (less than 0.05 is considered statistically significant) are shown in the legend.Different colours represent different segments.All values are per 100 000 population.APC -annual percentage change, DALYs -disability-adjusted life-years

Figure 2 .
Figure 2. Joinpoint regression analysis of global other STI excluding HIV incidence (Panel A), prevalence (Panel B), DALYs (Panel C), and mortality (Panel D) in the elderly aged 50-65 years from 1990 to 2019.The joinpoints have been labeled in the figure, and the corresponding APC and P-values (less than 0.05 is considered statistically significant) are shown in the legend.Different colours represent different segments.All values are per 100 000 population.APC -annual percentage change, DALYs -disability-adjusted life years, STI -sexually transmitted infections

Figure 3 .Figure 4 .Figure 5 .Figure 6 .
Figure 3. Stacked cube of incidence (Panel A) and prevalence (Panel B) rate of five other STI in 2019 based on gender and age group.In an age group, the left shows female and the right shows male.STI -sexually transmitted infections

Figure 9 .
Figure 9.The predictions of global prevalence rates for male and female from 2020 to 2030.HIV.Panel A. Female.Panel B. Male.Other STI excluding HIV.Panel C. Female.Panel D. Male.The black line represents the predicted mean prevalence rate, and the gradient area is its 95% confidence interval.STI -sexually transmitted infections

Table 2 .
Global rate and average annual percentage change (AAPC) in incidence per 100 000 population of HIV and other sexually transmitted infections (STI) excluding HIV from 1990 to 2019 globally and in different age groups, genders, sociodemographic index regions (SDI), and geographic regions

Table 2 .
continued of 5.59 (5.07 to 6.12), followed closely by the 65-69 years group with an AAPC of 5.44 (4.96 to 5.94).A slight decline was observed in other STI prevalence rate across all age brackets (Table3).Compared to 1990, DALYs and mortality rates across all four age groups showed a significant rise in 2019, almost doubling.Moreover, DALYs and mortality rates for other STI showed a marked reduction in all four age categories (

Table 3 .
Global rate and average annual percentage change in prevalence (AAPC) per 100 000 population of HIV and other sexually transmitted infections (STI) excluding HIV from 1990 to 2019 globally and in different age groups, genders, sociodemographic index (SDI) regions and geographic regions , panel A).The middle SDI regions display the most accelerated growth rates for prevalence, DALYs, and mortality when compared to other SDI regions, with AAPCs of 9.46(7.98to10.95), 6.88 (3.97 to 9.86), and 6.74 (3.8 to 9.76) respectively (Table 3, Table 4, Table 5).In terms of incidence number, the middle SDI region led in 2019, accounting for 71 830 cases (Table 2), making up 41.20% of the global incidence in individuals aged 50-69.For prevalence, the middle SDI region again topped in 2019, totalling 2 472 400 cases, which made up 33.72% of the global prevalence.

Table 4 .
Global rate and average annual percentage change (AAPC) in disability adjusted life years (DALYs) per 100 000 population of HIV and other sexually transmitted infections (STI) excluding HIV from 1990 to 2019 globally and in different age groups, genders, sociodemographic Index regions (SDI) and geographic regions

Table 5 .
Global rate and average annual percentage change (AAPC) in mortality per 100 000 population of HIV and other sexually transmitted infections (STI) excluding HIV from 1990 to 2019 globally and in different age groups, genders, sociodemographic Index (SDI) regions and geographic regions