Trends of HIV/AIDS Highlighted the Progresses and Challenges in Prevention and Control From 1990 to 2019

Background HIV/AIDS is a critical public health concern worldwide. This article aimed to demonstrate th trends of HIV/AIDS burden from 1990 to 2019. Methods Data was extracted from the Global Burden of Disease study (GBDs) 2019. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were estimated to quantify the trends at global, regional and national levels. Results During the period 1990-2004, the trend in incidence of HIV/AIDS was stable globally. Whereas the trends in prevalence, death and disability-adjusted life years (DALYs) had pronounced increasing trends, with the respective EAPCs were 7.47 (95%condence interval [CI]: 5.84 to 9.12), 10.85(95%CI: 8.90 to 12.84), and 10.40(95%CI: 8.47 to 12.36). Meanwhile, the pronounced increasing trends were seen in low-resource settings, particularly that of death in Oceania and South Asia, in which the respective EAPCs were 44.76 (95%CI: 40.81 to 48.82) and 40.82 (95%CI: 34.31 to 47.64). However, the global trends in incidence, death and DALYs of HIV/AIDS pronouncedly decreased from 2005 to 2019, with the respective EAPCs were −2.68(95%CI: −2.82 to −2.53), −6.73(95%CI: −6.98 to −6.47) and −6.75(95%CI: −6.95 to −6.54). Whereas prevalence showed increasing trend (EAPC: 0.71, 95%CI: 0.54 to 0.87). Decreasing trends of HIV/AIDS were observed in most regions and countries, particularly that of death and DALYs in Burundi respectively were −15.28 (95%CI: −16.08 to −14.47) and −15.07 (95%CI: −15.79 to −14.33). Conclusions Decreasing trends of HIV/AIDS were observed worldwide over the past 15 years. However, HIV/AIDS remains one of the most critical causes of health loss worldwide, which emphasized the effective prevention and control strategies.

. Other prevention interventions including early preventive intervention, o cial funding, enhancement in HIV/AIDS testing and education, were advocated to reduce the risk of HIV/AIDS transmission [8][9][10][11][12] . Despite the considerable achievements had made, the burden of HIV/AIDS remains a substantial challenge to global public health.
The Joint United Nations Programme on HIV/AIDS (UNAIDS) launched a target of ending the AIDS epidemic by 2030 13 . Therefore, it is necessary to track the trends of HIV/AIDS using the latest data from the Global Burden of Disease study (GBDs). In this study, the authors aimed to investigated the trends of HIV/AIDS from 1990 to 2019, which would inform the strategies of HIV/AIDS control.

Data source
Data on the HIV/AIDS incidence was derived from the Global Health Data Exchange (GHDx) (http://ghdx.healthdata.org/gbd-results-tool/). The disease burden of HIV/AIDS including incidence, prevalence, death, and disability-adjusted life years (DALYs), were extracted by sexes, age, sociodemographic index (SDI) areas, geographic regions, and countries from 1990 to 2019. According to the socio-demographic index (SDI), the world was categorized into low, low-middle, middle, high-middle, and high. The data was available in multiple geographic dimensions, including 21 geographic regions (e.g. East Asia, Oceania, and Caribbean), and 204 countries/territories (e.g. China, Brazil, and South Africa).
Data on Human Development Index (HDI) was downloaded from the United Nations Development Program (http://hdr.undp.org/en/ data).

Statistical analysis
Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were estimated to quantify the changing trends of disease. When involving discrepancies in the age structure of multiple populations over time, the ASR is a necessary and representative index. The ASR was calculated as the following formula: In the above formula, a i is the age-speci c rate in the i th age group, w is the number of people in the corresponding i th age group among the selected reference standard population, and A is the number of age groups. Estimated annual percentage changes (EAPC) is a widely accepted method for describing the magnitude of the trends in ASR 14,15 . A regression line is tted to the natural logarithm of the ASR. EAPC and its 95% con dence interval (CI) was calculated using the linear regression model using the following formula: where y: ln (ASR), and x: calendar year. When both EAPC value and its 95% CI > 0 meant an increasing trend, and both EAPC value and 95% CI < 0 meant a decreasing trend. While others signi ed that trend was stable over time. In order to detect factors in uencing EAPCs, a Pearson correlation analysis was used to analyzed the association between the EAPC and ASR in 1990, and HDI in 2019, respectively. Data was calculated using an R program (Version 3.6.2).

Trends in incidence of HIV/AIDS
Globally, the incident number of HIV/AIDS increased 28.62% since 1990. During the period 1990-2004, the overall age-standardized incidence rate (ASIR) of HIV/AIDS was relatively stable (Table 1, and Figure 1A).  Figure 1B). From 2005-2019, a decreasing trend in ASIR of HIV/AIDS was more obvious in females than that of males, with the EAPC of − 3.14 (95%CI: − 3.30 to − 2.98) ( Table 1). Among age groups, the highest increase in number of HIV/AIDS cases was observed in age group above 60 years (19.83%), and the highest decrease was in group aged under 5 years (−67.8%) (eTable 2 and eFigure 1A in the Additional le).Downward trend of ASIR were observed in low, low-middle, and middle SDI areas, particularly the rst one (EAPC = −5.29, 95%CI: −5.61 to −4.98). However, increasing trends were seen in high-middle and high SDI areas. At regional level, the trends declined in 8 geographic regions, and the largest ones were seen in Eastern Sub-Saharan Africa and East Asia, with the respective EAPCs were −5.66 (95%CI: −5.97 to −5.35) and −5.35 (95%CI: −6.31 to −4.37). However, increasing trends occured in 13 geographic regions, particularly Eastern Europe (EAPC= 12.31, 95%CI: 10.38 to 14.28) ( Table 1, and eFigure 1B-C in the Additional le). Among 204 countries/territories, the ASIR presented downward trends in 72 countries, and the largest one was in Burundi (EAPC = −12.93, 95%CI: −13.23 to −12.63), followed by Cambodia and Democratic Republic of the Congo. On the other hand, the ASIR showed increasing trends in 100 countries, particularly Kazakhstan (EAPC = 13.00, 95%CI: 11.52 to 14.50), followed by Russian Federation and Ukraine ( Figure Figure 2D, and eTable 9, eFigure 5D and 7D in the Additional le).
Globally, the number of DALYs due to HIV/AIDS was 47632. During the period 1990-2004, trends of HIV/AIDS burden, particularly prevalence, death and DALYs rapidly increasing globally. In the early 1990s, The HIV/AIDS epidemic was closely associated with poverty, poor Health infrastructure, lack of control policies, and the high prevalence of injection drug use and sexual transmission [16][17][18][19] . Increasing trends were mostly seen in the low and low-middle SDI areas, where existed poverty, drug use, low-levels education, and limited health systems 20 . Among geographic regions, Oceania, East Asia, and South Asia showed the largest increasing trends of HIV/AIDS, where the ART coverage was only 25.9%, far lower than that in global (40.6%) and low SDI countries (37.9%) 21 . At national level, Nepal, Papua New Guinea, and Lao People's Democratic Republic had the most pronounced increasing trends of HIV/AIDS burden. Furthermore, the situation had been exacerbated by tuberculosis co-infection and drug resistance 22 . In these countries, there were many obstacles to the control of HIV/AIDS, including shortage of capital investment, poor health infrastructure and education 23,24 . Whereas decreasing trends of HIV/AIDS were generally observed in developed region and countries, e.g. New Zealand and Australia, where had the early response to HIV/AIDS prevention in high-risk groups, high-level awareness, and the robust healthcare systems [25][26][27] .
However, decreasing trends of HIV/AIDS were observed worldwide over the past fteen years (2005-2019), which might be due to the effective prevention and control strategies established in recent years, such as poverty reduction, improvement in health infrastructure, and intensive international cooperation 28  pronounced decreasing trends were found in Sub-Saharan Africa countries included Burundi, Malawi, and Zimbabwe, probably due to the secondary education, medical circumcision in adolescents and children [36][37][38] . However, increasing trends of HIV/AIDS occurred in Eastern Europe and Central Asia, which was due to underdeveloped economy, unsound health system, and high risks of infectious diseases [39][40][41] . In the former Soviet countries, tuberculosis, drug use, and HIV infection were major public problems 42,43 , which probably generated the pronounced increasing trends in Georgia, Armenia, and Kazakhstan.
Considerable progress had been achieved in the prevention and control of HIV/AIDS, but there are neither cure nor an effective and safe vaccine for HIV/AIDS 44 , and the emergence of anti-HIV drug resistance brought substantial challenges 45,46 .
Serval limitations should be interpreted in this study:

Declarations
Ethical approval and consent to participate: Not applicable.

Consent for publication:
All authors consent for publication of the manuscript.
Availability of supporting data: All data during this study are included in this published article and its supplementary information les.
Competing interests: The authors declare no competing interests.     The distribution of EAPCs of HIV/AIDS burden at a national level during the period 1990-2004, including incidence (A), prevalence (B), death (C), and DALYs (D) Countries/territories with an extreme value were annotated. ASR, age-standardized rate; EAPC, estimated annual percentage change; DALYs, disabilityadjusted life-years. Note: The designations employed and the presentation of the material on this map do not imply the expression of any opinion whatsoever on the part of Research Square concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. This map has been provided by the authors.