Global,Regional,and National Burden of HIV and Drug-Susceptible Tuberculosis Co-Infection Among Adolescents and Young Adults (1990-2021)

Abstract

Background

HIV and drug-susceptible tuberculosis (DS-TB) co-infection severely affects adolescents and young adults (10-24 years), leading to a significant infectious disease burden, yet this age group remains overlooked. This study assessed the 1990-2021 global, regional, and national disease burden of HIV and DS-TB co-infection with a specific focus on adolescents and young adults (10-24 years).

Methods

The Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) estimates disaggregated by HIV status and TB drug susceptibility. Number and rates of the incidence, prevalence, and mortality of HIV and DS-TB co-infection from 1990 to 2021 at the global, regional, and national level among individuals aged 10-24 years were collected from GBD 2021. Trends were analyzed by sex and Sociodemographic Index (SDI).

Results

In 2021, over 100 000 new cases and nearly 20 000 deaths were recorded globally, with the highest burden in low-SDI regions and Southern Africa. Globally, all metrics initially increased, then declined after reaching their peak. Higher disease burden occurred in females than in males.

Conclusion

HIV and DS-TB co-infection remains a critical public health challenge for adolescents and young adults. Greater attention must be directed to prevention, treatment, and care among adolescents and young adults.

Plain Language Summary Title

The study reported the incidence, prevalence, and mortality of HIV and drug-susceptible tuberculosis (DS-TB) co-infection in people aged 10-24 years. Global data were used to better understand global trends and better control and prevent the spread of the disease.

Plain Language Summary

Why was the study done? HIV and drug-susceptible tuberculosis (DS-TB) co-infection imposes many adverse clinical outcomes on adolescents and young adults, leading to a significant infectious disease burden. However, there is a persistent trend of neglect concerning individuals aged 10-24 years. We aimed to identify the global, regional, and national disease burden of HIV and DS-TB co-infection in 10 to 24 years old from 1990 to 2021. What did the researchers do? We used data from the 2021 Global Burden of Disease Study to look at how often young people aged 10 to 24 around the world got, had, or died from HIV and DS-TB co-infection between 1990 and 2021. We further analyzed global trends by sex and a measure of a country's development level (Sociodemographic Index or SDI). What did the researchers find? In 2021, HIV and DS-TB co-infection caused 102,712 new cases, 184,481 prevalent cases, and 19,214 deaths globally in people aged 10 to 24 years. Overall, the rates of new cases, prevalent cases, and deaths related to HIV and DS-TB co-infection first went up over time, but then started going down. Young people in the world's least developed regions (Low SDI) and specifically in Southern Africa faced the highest rates of this double infection and death. The burden of these diseases was also higher on young women and girls than on young men and boys. What do the findings mean? This study has identified that HIV and DS-TB co-infection is still a serious health problem for 10 to 24 years old worldwide. We need to improve prevention, treatment, and care for this disease, with special focus on young people in this age group.

Keywords

HIV drug-susceptible tuberculosis adolescents young adults burden of disease

Introduction

Globally, human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection imposes a major global infectious disease burden, especially for children and adolescents. In the demographic under consideration, composed of individuals aged between 10 and 24 years, HIV and TB were responsible for 11% of mortalities.¹ Notably, Acquired Immunodeficiency Syndrome (AIDS) is the only infectious disease with an increasing burden over time.² Drug-susceptible TB (DS-TB) is defended as TB that is susceptible to isoniazid and rifampicin, which is the leading cause of death in patients with HIV, with the incidence of TB-related fatalities among HIV-positive patients reaching 217 000 in 2019.³ Global efforts are intensifying, including United Nations targets to end TB by 2030, and the WHO HIV Strategy 2022-2030 aiming to drastically reduce infections and deaths.^4,5 The high incidence rate of HIV and TB at the age of 10-24 years marks this period as crucial for prevention. Future epidemic progress hinges on controlling infections and disease within this generation.^2,6 However, specific needs in this group are often overlooked, despite their significant disease burden.²

The 10-24 age group exceeded 1.8 billion in 2021 (a quarter of the global population), projected to expand by about 7% by the year 2030.^7,8 Annually, an estimated 1.2 to 3 million young people develop TB, with potential infections 6 to 20 times higher than active disease prevalence.⁶ TB is the fifth leading cause of death for the 10 to 24 age group, with TB and HIV/AIDS together accounting for more than a fifth of fatalities from adolescence into early adulthood.⁹ In comparison to adults, adolescents and young adults are subject to elevated risks of treatment discontinuation, non-completion, and death, compounded by elevated financial and psychological burdens and complex support needs. Addressing these preventable diseases in youth is vital for their long-term health and national socioeconomic futures, forming a cornerstone for achieving global health goals by 2030.¹⁰ Despite their vulnerability, older children and adolescents remain marginalized in long-term health policies and programming.¹¹

HIV and DS-TB co-infection is driven by health, social, and economic determinants, such as poverty, undernutrition, housing conditions, and mental health. Critically, HIV-1 infection dramatically increases DS-TB risk, and DS-TB exacerbates HIV-1 replication and diversity.¹² While global incidence and mortality of HIV and DS-TB are declining overall due to socioeconomic improvements,^13,14 alarming increases persist in regions like Kenya.^15,16 WHO has highlighted that over half of young TB patients face barriers accessing care due to diagnostic and treatment challenges.¹⁷

A number of studies have recently been conducted that focus on the disease burden of HIV and TB co-infection. Wang Yaping and colleagues conducted a study on the burden of HIV and TB co-infection across all age groups.¹⁸ Similarly, Wang Longhao et al concentrated on HIV and DS-TB co-infection and conducted a related study.¹⁹ At present, however, there is a paucity of research on the global disease burden of HIV and DS-TB co-infection among adolescents and young adults. This group suffers the highest HIV and DS-TB co-infection risk and contributes significantly to transmission.² Therefore, this study aims to identify the global disease burden of HIV and DS-TB co-infection, with a particular focus on the 10-24 age demographic. The findings will inform decision-making processes and contribute to the enhancement of HIV and TB control strategies.

Methods

Study Design

This study constitutes a secondary analysis of repeated cross-sectional data. We utilized data obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 using the Global Health Data Exchange (GHDx) results tool. GBD 2021 is a comprehensive study of global health loss, providing detailed information on the burden and prevalence of 371 injuries and diseases, including HIV and DS-TB co-infection, encompassing 21 global regions and 204 countries and territories from 1990 to 2021. An international network of more than 10 000 collaborators from over 150 regions and countries provided, reviewed, or analyzed the available data to produce the GBD metrics. For GBD 2021, efforts were made to integrate a comprehensive range of global data into the projections as much as possible. GBD estimates integrate diverse data sources, including literature reviews, case notifications, and population-based surveys, as described in detail elsewhere.²⁰ The study is compliant with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) (Supplemental appendix).²¹ This study incorporated data from the GBD database, which includes information on individuals aged 10 to 24 years who underwent TB drug sensitivity testing and HIV serological testing from 1990 to 2021. The study exclusively included the GBD study team's final estimated data after standardization and adjustment, while excluding unprocessed data from the GBD study.

Case Definition

The classification of TB follows the International Statistical Classification of Diseases and Related Health Problems (ICD). This includes all forms of TB, both pulmonary and extrapulmonary, whether bacteriologically confirmed or clinically diagnosed. For TB, the ICD-10 codes are A10-A19.9, B90-B90.9, K67.3, K93.0, M49.0, P37.0, and the ICD-9 codes are 010-019.9, 137-137.9, 138.0, 138.9, 139.9, 320.4, 730.4-730.6. For HIV-TB, the ICD-10 code is B20.0. In the GBD 2021, TB incidence was estimated independently according to the results of drug sensitivity tests and HIV status. HIV and DS-TB co-infection is defined as TB (among HIV-positive individuals) that is susceptible to isoniazid and rifampicin.^20,22

Data Collection

For the 10-24 age group with HIV and DS-TB co-infection, data on the number and rates of incidence, prevalence, and mortality were obtained from the GHDx result tool (with 95% uncertainty intervals [UIs]), and these were then categorized by sex, region, and country. The GBD 2021 estimates of the global TB burden have been updated using improved data sources, estimation models, and statistical analysis methods. These updates adhere to the GATHER. The Disease Model Bayesian Meta-Regression (DisMoD-MR) tool (version 2.1) is based on the Bayesian Priors, Regularization, and Trimming (MR-BRT) model. It utilizes various input data sources, including annual case notifications, prevalence surveys, population-based TB surveys, and estimates of cause-specific mortality of TB to provide consistent disease burden estimates.²³ Detailed information on the disease modeling has been delineated in earlier studies.^23,24

In our research, we conducted an analysis of the incidence, prevalence, and mortality of HIV and DS-TB co-infection by country, territory, Sociodemographic Index (SDI) region, and Global Burden of Disease (GBD) region. The SDI serves as a composite indicator that incorporates the total fertility rate among individuals under 25 years, the average level of education for those aged 15 and older, and lag-distributed income per capita. This index provides insights into the developmental status pertinent to health outcomes.²⁵ For this study, we utilized the SDI to categorize the 204 countries and territories into 5 distinct groups: low, low-middle, middle, high-middle, and high SDI regions. Furthermore, these countries and territories were also classified into 21 GBD regions, which comprise countries and territories that are both geographically proximate and epidemiologically akin.²²

Statistical Analysis

Our study encompassed individuals aged from 10 to 24 years, examining the global disease burden of HIV and DS-TB co-infection across years, gender, and location. We calculated 95% UIs using 1000 draws from the posterior distribution, with the 2.5th and 97.5th percentiles as bounds. We evaluated the age-standardized rates of incidence, prevalence, and mortality for HIV and DS-TB co-infection among different sexes, regions, and countries, with rates expressed per 100 000 population. All statistical analysis progress was performed utilizing R software (version 4.3.3).

Results

Global Trends

Globally, incidence and prevalence have declined since their peaks around 2000, while mortality has decreased but remains slightly above 1990 levels. In 2021, there are an estimated 102 712 (95% UI: 91 445 to 114 908) new cases of HIV and DS-TB co-infection in young people aged 10 to 24 years globally, with an incidence of 5.44 (95% UI: 4.84 to 6.09) per 100 000 population, which was lower than that in 1990. Global incidence peaked in 2001 and has declined since. Prevalence in 2021 was estimated at 184 481 (95% UI: 162 933 to 206 706) cases globally, with a prevalence of 9.77 (95% UI: 8.63 to 10.95) per 100 000 population, and decreased compared with 1990. It decreased after peaking at 28.56 (95% UI: 25.27 to 31.46) per 100 000 population in 2000. Mortality was 19 214 (95% UI: 14 966 to 24 109) deaths in 2021, with a rate of 1.02 (95% UI: 0.79 to 1.28) per 100 000 population, representing a small increase from 1990. The global mortality rate peaked in 2003 and has since declined, but remains above 1990 levels (Tables 1 and 2).

Table 1.

Incidence, Prevalence, and Mortality Rates at the Global and Regional Level in 1990 and 2021.

	Incidence	Prevalence	Mortality
Location	Rates per 100 000 Population (Age-standardized), 1990 (95% UIs)	Rates per 100 000 Population (Age-standardized), 2021 (95% UIs)	Rates per 100 000 Population (Age-standardized), 1990 (95% UIs)	Rates per 100 000 Population (Age-standardized), 2021 (95% UIs)	Rates per 100 000 Population (Age-standardized), 1990 (95% UIs)	Rates per 100 000 Population (Age-standardized), 2021 (95% UIs)
Global	7.67	5.44	15.03	9.77	0.81	1.02
	(6.82 to 8.55)	(4.84 to 6.09)	(13.28 to 16.64)	(8.63 to 10.95)	(0.57 to 1.22)	(0.79 to 1.28)
SDI
High-middle SDI	0.57	0.41	0.71	0.67	0.057	0.043
	(0.50 to 0.65)	(0.36 to 0.47)	(0.61 to 0.82)	(0.58 to 0.77)	(0.043 to 0.074)	(0.028 to 0.061)
Low-middle SDI	11.32	5.25	21.19	9.32	1.01	1.03
	(9.77 to 13.02)	(4.60 to 6.00)	(18.39 to 24.14)	(8.21 to 10.48)	(0.71 to 1.51)	(0.76 to 1.40)
High SDI	0.45	0.067	0.64	0.081	0.056	0.0085
	(0.38 to 0.53)	(0.059 to 0.077)	(0.56 to 0.74)	(0.070 to 0.093)	(0.038 to 0.073)	(0.0056 to 0.013)
Middle SDI	2.80	5.28	4.20	8.45	0.19	0.60
	(2.46 to 3.12)	(4.71 to 5.91)	(3.69 to 4.80)	(7.47to 9.35)	(0.15 to 0.24)	(0.46 to 0.72)
Low SDI	38.36	11.75	83.12	22.87	4.83	2.72
	(34.20 to 42.46)	(10.31 to 13.24)	(73.38 to 91.99)	(19.99 to 25.77)	(3.24 to 7.57)	(2.16 to 3.35)
Regions
Central Europe	0.35	0.16	0.42	0.20	0.06	0.03
	(0.27 to 0.41)	(0.14 to 0.19)	(0.28 to 0.53)	(0.17 to 0.23)	(0.04 to 0.07)	(0.02 to 0.05)
East Asia	0.23	0.53	0.35	1.07	0.01	0.03
	(0.15 to 0.28)	(0.45 to 0.60)	(0.22 to 0.42)	(0.88 to 1.25)	(0.00 to 0.01)	(0.02 to 0.05)
Oceania	0.31	2.17	0.55	7.44	0.02	0.54
	(0.21 to 0.37)	(1.92 to 2.42)	(0.40 to 0.75)	(6.58 to 8.28)	(0.01 to 0.03)	(0.33 to 0.81)
Central Asia	0.41	0.13	0.66	0.18	0.04	0.02
	(0.35 to 0.47)	(0.10 to 0.16)	(0.53 to 0.76)	(0.14 to 0.23)	(0.03 to 0.04)	(0.01 to 0.03)
Southeast Asia	1.95	2.78	3.09	5.38	0.21	0.30
	(1.77 to 2.13)	(2.52 to 3.04)	(2.75 to 3.41)	(4.82 to 5.94)	(0.14 to 0.30)	(0.23 to 0.39)
High-income Asia Pacific	0.20	0.11	0.19	0.08	0.01	0.01
	(0.04 to 0.26)	(0.09 to 0.13)	(0.05 to 0.24)	(0.06 to 0.09)	(0.01 to 0.01)	(0.01 to 0.01)
Western Europe	0.92	0.05	1.18	0.05	0.15	0.01
	(0.79 to 1.09)	(0.04 to 0.05)	(1.01 to 1.36)	(0.04 to 0.06)	(0.10 to 0.20)	(0.01 to 0.02)

Australasia	0.30	0.02	0.28	0.02	0.02	0.00
	(0.26 to 0.36)	(0.02 to 0.02)	(0.24 to 0.33)	(0.01 to 0.02)	(0.01 to 0.02)	(0.00 to 0.00)
Eastern Europe	1.08	0.43	1.01	0.39	0.08	0.03
	(0.93 to 1.25)	(0.30 to 0.57)	(0.87 to 1.15)	(0.28 to 0.51)	(0.05 to 0.12)	(0.02 to 0.06)
Southern Latin America	2.46	0.87	3.57	1.11	0.24	0.20
	(2.15 to 2.81)	(0.75 to 1.01)	(3.13 to 4.05)	(0.95 to 1.27)	(0.23 to 0.24)	(0.13 to 0.26)
Central Latin America	1.90	0.91	3.34	1.47	0.35	0.16
	(1.71 to 2.11)	(0.80 to 1.04)	(2.95 to 3.76)	(1.28 to 1.70)	(0.29 to 0.40)	(0.11 to 0.24)
High-income North America	0.45	0.02	0.66	0.03	0.05	0.00
	(0.39 to 0.52)	(0.02 to 0.03)	(0.56 to 0.77)	(0.02 to 0.03)	(0.03 to 0.08)	(0.00 to 0.01)
Andean Latin America	4.42	1.63	5.96	2.07	0.18	0.19
	(3.69 to 5.17)	(1.37 to 1.90)	(4.71 to 7.37)	(1.73 to 2.45)	(0.18 to 0.19)	(0.11 to 0.31)
Caribbean	6.86	2.06	10.41	2.79	1.74	0.51
	(6.16 to 7.71)	(1.82 to 2.34)	(9.03 to 11.64)	(2.39 to 3.23)	(1.05 to 3.01)	(0.27 to 1.41)
North Africa and Middle East	0.27	0.28	0.30	0.36	0.02	0.03
	(0.23 to 0.31)	(0.25 to 0.32)	(0.24 to 0.35)	(0.31 to 0.41)	(0.01 to 0.03)	(0.02 to 0.04)
Eastern Sub-Saharan Africa	92.91	28.16	203.42	52.66	11.98	6.59
	(82.05 to 104.13)	(24.52 to 31.95)	(177.60 to 227.79)	(45.90 to 60.11)	(7.96 to 19.04)	(5.17 to 8.22)
Central Sub-Saharan Africa	40.82	12.23	95.97	27.06	4.91	2.71
	(36.26 to 45.38)	(10.86 to 13.67)	(84.85 to 109.14)	(23.98 to 30.32)	(2.97 to 8.68)	(1.94 to 3.71)
Tropical Latin America	6.09	2.34	8.65	2.58	0.73	0.20
	(5.23 to 7.02)	(1.97 to 2.75)	(7.45 to 9.84)	(2.20 to 2.99)	(0.54 to 0.92)	(0.12 to 0.30)
South Asia	0.34	1.16	0.50	1.80	0.00	0.12
	(0.28 to 0.41)	(0.96 to 1.35)	(0.39 to 0.61)	(1.51 to 2.10)	(0.00 to 0.01)	(0.08 to 0.18)
Southern Sub-Saharan Africa	167.01	130.62	250.40	206.10	8.73	17.86
	(143.89 to 193.74)	(115.09 to 147.35)	(211.73 to 290.20)	(181.43 to 229.93)	(6.05 to 13.01)	(14.24 to 21.58)
Western Sub-Saharan Africa	21.41	7.68	47.82	15.62	2.30	1.76
	(18.98 to 23.52)	(6.74 to 8.70)	(41.91 to 53.12)	(13.66 to 17.59)	(1.61 to 3.34)	(1.21 to 2.58)

Values in parentheses are 95% uncertainty intervals.

Table 2.

Number of New Cases, Cases and Mortality in 21 GBD Regions in 1990 and 2021.

	Incidence	Prevalence	Mortality
	Number of Cases, 1990	Number of Cases, 2021	Number of Cases, 1990	Number of Cases, 2021	Number of Cases, 1990	Number of Cases, 2021
Global	118 618	102 712	232 530	184 481	12 523	19 214
	(105 509 to 132 355)	(91 445 to 114 908)	(205 480 to 257 490)	(162 933 to 206 706)	(8878 to 18 899)	(14 966 to 24 109)
Central Europe	103	30	122.09	36	17	6
	(80 to 121)	(26 to 34)	(83 to 153)	(31 to 42)	(13 to 20)	(4 to 9)
East Asia	855	1289	1294	2611	30	82
	(574 to 1028)	(1093 to 1466)	(816 to 1580)	(2137 to 3029)	(5 to 54)	(50 to 117)
Oceania	6	87	11	300	0	22
	(4 to 8)	(77 to 98)	(8 to 16)	(265 to 334)	(0 to 0)	(13 to 33)
Central Asia	81	29	130	40	7	4
	(70 to 93)	(22 to 36)	(106 to 151)	(30 to 50)	(5 to 9)	(2 to 6)
Southeast Asia	2895	4753	4584	9202	310	514
	(2632 to 3162)	(4307 to 5206)	(4073 to 5065)	(8247 to 10 158)	(208 to 446)	(398 to 666)
High-income Asia Pacific	83	29	78	20	2	2
	(18 to 108)	(24 to 33)	(21 to 101)	(17 to 24)	(2 to 2)	(2 to 2)
Western Europe	757	33	967	36	125	9
	(650 to 894)	(28 to 38)	(830 to 1116)	(31 to 41)	(84 to 165)	(6 to 14)
Australasia	15	1	14	1	1	0
	(12 to 17)	(1 to 1)	(12 to 16)	(1 to 1)	(0 to 1)	(0 to 0)
Eastern Europe	511	141	476	128	37	11
	(438 to 591)	(100 to 188)	(413 to 543)	(91 to 168)	(23 to 55)	(5 to 21)
Southern Latin America	326	133	472	1610	32	31
	(285 to 372)	(115 to 156)	(414 to 536)	(146 to 195)	(31 to 32)	(20 to 40)
Central Latin America	1031	590	1814	959	191	107
	(928 to 1146)	(519 to 675)	(1599 to 2039)	(832 to 1105)	(158 to 216)	(69 to 155)
High-income North America	274	16	405	20	31	3
	(236 to 319)	(14 to 19)	(346 to 471)	(17 to 24)	(19 to 48)	(2 to 4)
Andean Latin America	544	281	733	357	23	32
	(454 to 636)	(237 to 328)	(580 to 907)	(298 to 423)	(22 to 24)	(19 to 53)
Caribbean	733	234	1111	316	186	58
	(658 to 824)	(206 to 265)	(965 to 1243)	(271 to 366)	(112 to 322)	(30 to 160)
North Africa and Middle East	298	460	323	578	19	43
	(250 to 343)	(404 to 527)	(266 to 383)	(501 to 663)	(12 to 32)	(29 to 61)
Eastern Sub-Saharan Africa	57 636	40 960	126 188	76 589	7434	9591
	(50 896 to 64 596)	(35 666 to 46 465)	(110 171 to 141 307)	(66 757 to 87 416)	(4939 to 11 809)	(7516 to 11 951)
Central Sub-Saharan Africa	7066	5496	16 610	12 160	849	1217
	(6276 to 7854)	(4880 to 6143)	(14 685 to 18 889)	(107 710 to 13 626)	(514 to 1503)	(872 to 1666)
Tropical Latin America	2915	1186	4140	1305	349	99
	(2501 to 3361)	(997 to 1391)	(3567 to 4709)	(1113 to 1513)	(258 to 441)	(61 to 152)
South Asia	1149	6077	1665	9479	12	645
	(948 to 1361)	(5064 to 7119)	(1305 to 2038)	(7943 to 11 034)	(5 to 28)	(404 to 943)
Southern Sub-Saharan Africa	28 531	28 493	42 777	44 961	1492	3896
	(24 581 to 33 098)	(25 105 to 32 143)	(36 172 to 49 577)	(39 578 to 50 159)	(1034 to 2222)	(3107 to 4707)
Western Sub-Saharan Africa	12 810	12 393	28 617	25 213	1376	2842
	(11 361 to 14 077)	(10 876 to 14 034)	(25 081 to 31 791)	(22 042 to 28 377)	(966 to 1997)	(1959 to 4163)

Values in parentheses are 95% uncertainty intervals.

SDI Regional Trends

The incidence rate, prevalence rate, and mortality rate are lowest in high SDI regions and highest in low SDI regions in 2021, with the low SDI region beginning to decline earliest. The middle SDI region was the only one showing an increase in incidence, prevalence, and mortality from 1990 to 2021. In 2021, the incidence in the high SDI region was consistently decreasing, and the middle SDI region was the last to decline until 2005. The time of mortality change in the low-middle SDI and high-middle SDI regions was also earlier, in 1999 and 2000, respectively. The middle SDI region was the last to see a decline until 2006. The mortality rate in the low-middle SDI region was slightly higher than in 1990 (Figure 1).

Figure 1.

Time trends in incidence (A), prevalence (B), and mortality (C) globally and in 5 SDI regions from 1990 to 2021.

Geographic Regional Trends

Of the 21 GBD regions, Sub-Saharan Africa, particularly Eastern and Southern regions, bore the highest burden of disease in 2021. Eastern Sub-Saharan Africa had the highest number of new cases (40 960; 95% UI: 35 666 to 46 465), cases (76 589; 95% UI: 66 757 to 87 416), and deaths (9591; 95% UI: 7516 to 11 951) (Table 2). Southern Sub-Saharan Africa had the highest incidence (130.62 per 100 000 population; 95% UI: 115.09 to 147.35), prevalence (206.10 per 100 000 population; 95% UI: 181.43 to 229.93), and mortality rates (17.86 per 100 000 population; 95% UI: 14.24 to 21.58). Central Sub-Saharan Africa and Western Sub-Saharan Africa also had high rates (Table 1, Figure 2). The global SDI was 0.67 in 2021; 4 regions had higher incidence rates, prevalence rates, and mortality rates than the global mean, whereas 17 regions had lower rates than the global mean (Figure 3).

Figure 2.

Incidence (A), prevalence (B), and mortality (C) in 2021, by 21 GBD regions.

Figure 3.

Incidence (A), prevalence (B), and mortality (C) rates from 1990 to 2021.

Gender Differences

The most pronounced gender differences in incidence, prevalence, and mortality are observed in Sub-Saharan Africa, where females consistently exhibit higher rates than males. Figure 4 shows the differences in the incidence, prevalence, and mortality of HIV and DS-TB co-infection in young people aged 10 to 24 years by gender. The most pronounced gender differences are concentrated in Southern sub-Saharan Africa. Furthermore, gender differences are also significant in Eastern, Central, and Western Sub-Saharan Africa. Evident gender disparities are also observed in Oceania, the Caribbean, and South Asia.

Figure 4.

Gender differences in incidence (A), prevalence (B), and mortality (C) in 2021, by 21 GBD regions.

Discussion

Until 2021, the prevalence and burden of HIV and DS-TB co-infection remain concerning. Consistent with previous research findings,^18,19 this study further demonstrates that the disease burden in the middle SDI region has increased rather than decreased, and that Sub-Saharan Africa consistently bore the highest disease burden. It has been established through previous studies that African regions exhibit the highest rates of HIV and TB co-infection. People living with HIV (PLHIV) have been found to be 18 times more likely to develop TB in comparison to those not living with HIV (non-PLHIV). Furthermore, high-HIV regions have been observed to experience increased TB recurrence.^26–28 A previous study has found that HIV infection rates among individuals aged 10 to 24 years declined significantly in 1998,²⁹ which may explain why the incidence, prevalence, and mortality of HIV and DS-TB co-infection began to decrease after peaking between 2000 and 2003.

It was observed that the above 3 indicators were generally higher in women than in men worldwide. In the case of the same viral load, the risk of AIDS in women is 1.6 times that in men,³⁰ possibly due to the stronger immune activation response in women.³¹ The data on drug response indicated that the treatment responses and outcomes were similar in men and women; women were more susceptible to adverse events associated with antiretroviral treatment, as reflected by lower treatment adherence and higher rates of treatment discontinuation, and social and behavioral factors may play an important role in this process.³² The gender inequalities of women in preventing disease and seeking care should also be highlighted.

HIV damages the immune system, significantly increasing susceptibility to TB and accelerating its progression. The age group of 10 to 24 years faces a particularly high HIV/AIDS burden. Despite a decline in recent years, the burden of HIV/AIDS patients has not yet returned to 1990 levels.^25,33 HIV and TB co-infection notification rises throughout adolescence, with nearly 50% of children/adolescents on TB treatment testing HIV-positive. They face high risks of treatment discontinuation, non-completion, and death, compounded by higher financial and psychological burdens and complex support needs. It is vital to emphasize that the global promotion of HIV and TB prevention, treatment, and care services is of paramount importance, particularly for adolescents and young adults. Local governments, especially in less developed countries, should strengthen health education for people to improve comprehensive HIV/TB knowledge and reduce infection risk.

Low-SDI regions showed rapid health gains over 22 years, suggesting effective health investments in lower-income countries. But at the same time, the progress in high SDI countries is remarkable, with large regional disparities in disease burden remaining in 2021, likely due to numerous health inequities. First of all, health inequity is reflected in the professionalism of medical workers. Tiruneh and colleagues found that less than half of the health care workers in Ethiopia had good TB infection control practices.³⁴ Vukugah and colleagues also found that the level of knowledge, attitude, and practice of healthcare workers regarding childhood TB management in Cameroon was unsatisfactory.³⁵ Beyond the professionalism of medical workers, medical professionals face certain gaps. In Uganda, over 90% of TB patients required multiple healthcare visits (an average of 4) for diagnosis, with less than 5% diagnosed on their first visit. Most of them were only diagnosed after constitutional symptoms appeared.³⁶ Efforts are needed to enhance the knowledge and skills training for healthcare workers, and the world should strengthen the construction of medical infrastructure in countries with low economic development levels to enhance the diagnosis and early treatment initiation for HIV and TB patients.

It is hypothesized that economic recession may be a contributing factor to the increased disease burden of HIV and DS-TB co-infection. Brazil, a high TB burden country, saw substantial case increases during its 2015-2019 recession, disproportionately affecting youth.³⁷ Nearly 20% of Brazilian children and adolescents aged 10 to 24 years receiving TB treatment from 2015 to 2018 experienced adverse outcomes like treatment failure or death.³⁸ The direct costs of HIV and TB treatment in children are higher than those in adults. Additional burdens include: pediatric specialists concentrated in urban areas creating geographic barriers; the need for parental accompaniment; and indirect costs from lost school/work time.³⁹ Countries with lower economic development levels need to bear more medical costs, which eventually leads to delayed or interrupted HIV/TB treatment in these countries.

HIV- and TB-related stigma is also a concern, and it is a barrier for patients to seek and adhere to treatment. TB is often associated with HIV because of a lack of knowledge about the disease and belief in myths about the etiology of TB.³⁹ TB stigma is present in 82% of TB patients in Zambia. People often use “kanayaka” to describe people living with HIV as a warning to avoid contact, meaning “a red light that never turns off,” and this label is also used for TB patients. Some patients and many of their relatives and neighbors believe that HIV and TB are the same disease. Many people believe that TB patients also have negative HIV-related attributes, such as immorality and promiscuous behavior, and that TB patients are always co-infected with HIV. This stigma is common in children, and children affected by both HIV and TB do not understand and feel uneasy about their social environment, which increases the additional burden of stigma.⁴⁰ The stigma of HIV and TB co-infected patients hinders their health-seeking behavior, and they choose not to wear masks or hide their illness for fear of discrimination, which ultimately leads to delayed treatment and increased risk of transmission.

Persistent disparities in disease burden exist across countries with different SDI levels. Challenges intensify as large-scale immigration, driven by conflict and globalization, strains these systems.⁴¹ The study found a sharp rise in TB incidence within conflict zones and neighboring countries. For instance, the Syrian war displaced millions to Lebanon, Iraq, and Turkey, significantly increasing TB cases and transmission among refugees and host communities.⁴² TB poses a major threat to crisis-affected populations, with over 85% of refugees originating from or residing in high TB burden countries.⁴³ It is imperative to acknowledge the significance of children in global affairs, as evidenced by the United Nations Children's Fund (UNICEF) report in 2023, which revealed that approximately 1 in 4 children worldwide reside in or are displaced due to conflict.⁴⁴ A Malaysian study found 12.8% of refugee children had latent tuberculosis infection.⁴⁵ Fleeing violence leads to poor living conditions, malnutrition, stress, and immunodeficiency, heightening susceptibility to diseases like TB and HIV.⁴⁶

Our study also has some limitations. Firstly, the GBD database has some missing data resources in some countries or regions, which may affect the accuracy and reliability of the results of this study. Second, both HIV and DS-TB have an incubation period. The incubation period of some HIV sufferers is very long, even more than 15 years, which may lead to an underestimation of GBD data. Third, our classification and analysis according to geographic region or SDI can only illustrate the overall burden of disease in this region, and the results in our study are not sufficient to represent the prevalence of disease in each country under this region. Finally, only one type of TB, DS-TB, was included in our study, excluding other TB types.

Conclusion

In conclusion, HIV and DS-TB co-infection remains a global health concern. From 1990 to 2021, the global burden of disease decreased, and the health gains in low SDI regions increased rapidly. However, the burden increased in middle-SDI regions, contrary to global trends. Sub-Saharan Africa remains the region with the highest disease burden. It is imperative that healthcare providers direct their attention towards young people aged 10-24 years, with a view to improving system investment, strengthening preventive measures, and developing appropriate treatment methods. It is absolutely necessary to enhance the comprehensive management of HIV and DS-TB, and to proactively promote the prevention, treatment, and care of the disease.

Supplemental Material

sj-pdf-1-jia-10.1177_23259582261449285 - Supplemental material for Global, Regional, and National Burden of HIV and Drug-Susceptible Tuberculosis Co-Infection Among Adolescents and Young Adults (1990-2021)

Supplemental material, sj-pdf-1-jia-10.1177_23259582261449285 for Global, Regional, and National Burden of HIV and Drug-Susceptible Tuberculosis Co-Infection Among Adolescents and Young Adults (1990-2021) by Junhui Wu, Guangqi Han, Disha Zhu, Weixuan Wang and Shaomei Shang in Journal of the International Association of Providers of AIDS Care (JIAPAC)

Footnotes

Acknowledgments

The authors appreciate the work of the GBD Study 2021 collaborators.

ORCID iDs

Guangqi Han

Disha Zhu

Weixuan Wang

Shaomei Shang

Ethical Approval and Informed Consent

The GBD protocol has been approved by the University of Washington's research ethics board, and the study is conducted in full compliance with the university's policies and applicable federal, state, and local regulations. This study constitutes a secondary analysis, which was carried out in accordance with the GBD protocol. Informed consent was waived due to the use of deidentified data.

Authors Contributions

Junhui Wu: Study design; data collection and analysis.

Guangqi Han: Study design; Writing.

Disha Zhu: Writing.

Weixuan wang: Writing.

Shaomei Shang: Study design.

Each author is expected to have made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or have drafted the work or substantively revised it.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (No. 72404008) and National Science and Technology Innovation 2030, Noncommunicable Chronic Diseases-National Science and Technology Major Project (Grant No. 2024ZD0524300, 2024ZD0524306). The funding source did not play any role in the design, data collection, analysis, interpretation of data, writing, or decision to submit the article for publication.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplemental Material

Supplemental material for this article is available online.

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