INTRODUCTION — The acquired immunodeficiency syndrome (AIDS) was first recognized among men who have sex with men in the United States in 1981 [1,2]. While initially limited, infection with the human immunodeficiency virus (HIV) has literally exploded over the past four decades to become the worst pandemic of the 20th century. With more than 50 million fatalities, the AIDS epidemic now ranks alongside the influenza pandemic of the early 1900s and the Bubonic plague of the 14th century in terms of fatalities . The impact of this disease on human suffering, cultures, demographics, economics, and even politics has been felt in nearly every society across the globe.
The initial optimism that followed the discovery of HIV, the development of diagnostic assays to help monitor the epidemic, the prophylaxis of opportunistic infections, the identification of effective antiretroviral drugs, and the prevention of perinatal transmission has been tempered by the stark reality and magnitude of the global HIV pandemic. The pandemic continues to spread relentlessly and to consolidate in many other locations. In some countries in sub-Saharan Africa, the AIDS pandemic had caused a dramatic decline of life expectancy that started to rebound with access to antiretrovirals.
This topic reviews worldwide statistics on the global HIV pandemic, modes of transmission, and the introduction of antiretroviral therapy (ART) into resource-limited settings. Updated information on global statistics is available on the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United States Centers for Disease Control and Prevention (CDC) websites. The clinical impact of ART on morbidity and mortality and the prevention of HIV are discussed in detail elsewhere. (See "Use and impact of antiretroviral therapy for HIV infection in resource-limited settings" and "HIV infection: Risk factors and prevention strategies" and "When to initiate antiretroviral therapy in persons with HIV", section on 'Universal treatment'.)
ORIGIN OF THE HIV PANDEMIC — While AIDS was only recognized in 1981, molecular phylogenetic studies indicate that HIV was present in Central and West Africa since the early 1900s, likely in localized populations . The current pandemic may have emerged from these populations in the mid-1900s with improved access to transport and other societal changes .
Zoonotic transmission — Molecular phylogenetic studies suggest that HIV evolved from a lentivirus, simian immunodeficiency virus (SIV), which has been found in some subspecies of monkeys from Bioko (an island off the African coast) and some subspecies of chimpanzees in Cameroon [6,7]. Researchers believe that all the SIV strains infecting primates across Africa diverged from a common ancestor between 32,000 and 78,000 years ago .
Several lines of evidence support zoonotic transmission of primate lentiviruses into humans [6,8]:
●Similarities in viral genome between SIV and HIV
●Prevalence in the natural host
●Geographic association between the animal reservoir and emergence of human cases
●Plausible route of transmission
Direct evidence of simian-to-human transmission is still missing but is inferred by the known practice of hunting chimpanzees for food ("bushmeat"), particularly in Western Africa . Unlike other more readily transmitted zoonoses, important viral adaptations may have been required for HIV to infect humans. These adaptations may have included the acquisition of viral regulatory genes such as vpu, vif, nef, and tat, and structural genes, gag and env . Observations from wild primate populations indicate that SIV, like HIV-1, is associated with progressive CD4 cell loss, lymphatic tissue destruction, and premature death [9,10].
Molecular epidemiology of HIV — Worldwide, there are two types of HIV: HIV-1, which originated from SIV strains in apes, and HIV-2, which originated from an SIV strain in sooty mangabey monkeys. HIV-1, the most prominent type, is further divided phylogenetically into different groups and subtypes. The main clinical implications of these different types of HIV are that infection with HIV-2 appears to have a more indolent natural history than HIV-1 and is intrinsically resistant to certain antiretroviral agents. Different subtypes of HIV-1 may also differ in the rate of transmission or disease progression [11-14]. Additionally, the multiple types and groups pose challenges for development of an effective and inclusive vaccine.
HIV-1 consists of four distinct viral groups, each of which resulted from a different zoonotic transmission event [15,16]. Groups M, N, and O were transmitted from chimpanzees and group P from gorillas. Group M ("Main") HIV is considered the pandemic strain and comprises the vast majority of strains of HIV, whereas the other groups have much more limited geographic distribution [8,17]. Viruses from group M are subsequently divided into nine distinct subtypes or clades (A-D, F-H, J-K) and recombinants of the subtypes, termed circulating recombinant forms (CRF). Subtype C accounts for almost half of the HIV-1 infections worldwide and predominates in Southern Africa and India (figure 1) [18-20]. Subtype B (which includes the highly virulent VB variant) predominates in North America, Western and Central Europe, the Caribbean, and Latin America .
Group O ("Outlier") represents far fewer strains, approximately one percent of global infections, and is geographically limited to West Africa (specifically Cameroon, Gabon, and Equatorial Guinea). Group N ("non-M/non-O") is represented by very few isolates and has only been documented in Cameroon. Group P, a novel HIV virus closely related to SIV strains found in gorillas, was discovered in 2009 from a woman in Cameroon . As of 2011, group P virus has been identified in only one other individual, also in Cameroon [16,22].
HIV-2 (groups A through H) is estimated to cause approximately five percent of global HIV infections. In particular, it is an important cause of infection in West Africa, and areas with historic ties to West Africa, such as Portugal, Spain, Goa, and India. The epidemiology of HIV-2 is discussed in detail elsewhere. (See "Epidemiology, transmission, natural history, and pathogenesis of HIV-2 infection".)
WORLDWIDE STATISTICS — Since its recognition in 1981, the pandemic has reached every country and nearly all populations throughout the world.
General statistics — By the end of 2021, the reported statistics on the global burden of HIV were the following [23,24]:
●38.4 million adults and 1.7 million children (<15 years old) were living with HIV/AIDS.
●1.5 million adults and 160,000 children had been newly infected with HIV that year.
●552,000 adults and 98,000 children died of AIDS that year.
The overall prevalence of HIV globally appears to have stabilized (at 0.7 percent) but continues to increase in some countries, likely due to increased survival of infected people because of antiretroviral treatment. However, the 2021 incidence of new HIV infections represents a decline of 54 percent from 2001, when there were 3.4 million new infections.
Nearly 60 percent of the world's population that has HIV is in sub-Saharan Africa. Countries in sub-Saharan Africa and the Caribbean have the highest national rates of adult HIV prevalence. As an example, in 2021, the adult HIV prevalence ranged from <0.1 percent in the Middle East and North Africa to 7 percent in sub-Saharan Africa overall, and it exceeded 25 percent in some sub-Saharan countries, such as Botswana, Lesotho, and Swaziland [23,24]. Part of this disparity can be attributed to the maturity of the epidemics in Africa and the more recent introduction of HIV into some other areas of the world.
Children bear a substantial proportion of the burden of HIV, both directly and indirectly. An estimated 1.7 million children are living with HIV/AIDS worldwide [23,24]. Of the 160,000 infants and children with HIV in 2021, 70 percent were born in sub-Saharan Africa, 25 percent in Southeast Asia, and the remainder in Latin America and the Caribbean [24,25]. Additionally, it is estimated that 25 million children have been orphaned by the premature death of both parents due to AIDS, placing enormous responsibilities on communities. With escalation of the pandemic in Southeast Asia and Eastern Europe, these numbers are only likely to increase, unless more aggressive prevention campaigns and interventions programs intercede to slow the pace of the pandemic. (See "Prevention of vertical HIV transmission in resource-limited settings".)
Worldwide, HIV/AIDS has been one of the top 10 causes of death in the 2010s, mainly driven by the mortality associated with HIV in sub-Saharan Africa, where it was the primary cause of death . However, due to marked increase in access to antiretroviral therapy (ART; approximately 28.7 million people on treatment), AIDS-related mortality has declined by 45 percent since 2010.
Sub-Saharan Africa — Approximately 10 percent of the world’s population lives in sub-Saharan Africa, but the region is home to almost two-thirds of the world’s population with HIV . The overall HIV prevalence rate in this region is 6.7 percent, and it exceeds 25 percent in some countries [23,24,27]. The highest HIV prevalence rates in the world are found in Swaziland (27.2 percent). Of the population with HIV within sub-Saharan Africa, 25 percent are in South Africa and 13 percent in Nigeria .
●Trends in cases – Nevertheless, the largest epidemics in sub-Saharan Africa (South Africa, Nigeria, Ethiopia, Zambia, and Zimbabwe) have either stabilized or are showing signs of decline. The decrease in new HIV infections since 2010 is larger in Eastern and Southern Africa than in any other region. The number of new HIV infections in Eastern and Southern Africa dropped from 1.1 million in 2010 to 670,000 in 2021. However, some countries, such as Ethiopia and Madagascar, actually experienced increases in the number of new infections over the same time period.
●Heterosexual transmission and burden in females – HIV infection in sub-Saharan Africa is generalized epidemic and is mostly related to heterosexual transmission. In 2021, females accounted for 59 percent of new HIV infections in the region [23,24,28]. The sex discrepancy is particularly evident among adolescents and young females; the HIV incidence among females aged 15 to 24 years is 2.5 times higher than that among males of the same age. Much of heterosexual transmission occurs between established partners. As an example, in a study of more than 4000 adult men and women in Rwanda and Zambia who underwent voluntary counseling and testing for HIV, an estimated 55 to 93 percent of new heterosexually acquired HIV infections occurred within serodiscordant marital or cohabiting relationships . Sex workers represent a high-risk group in sub-Saharan Africa. In a systematic review, the estimated prevalence of HIV among female sex workers in the region was 11.8 percent; compared with the general female population, the odds of HIV infection in a sex worker was 13.5 (95% CI 10-18.1) .
●Other key populations – A substantial proportion (roughly one-quarter) of new infections are among other key populations and their sexual partners. Specifically, MSM and transgender women represent high-risk groups . In a study in eight sub-Saharan African countries, 33 percent of transgender women said they had been physically attacked at some point, 28 percent had been raped, and 27 percent said they were too afraid to use health care services .
Latin America and the Caribbean
●The Caribbean – After sub-Saharan Africa, the Caribbean has the second highest HIV prevalence rates in the world [23,24]. In 2021, the 16 countries in the Caribbean region accounted for 330,000 people living with HIV; overall HIV prevalence was 1.1 percent. There have been declines in new HIV infections and AIDS-related deaths of 29 and 37 percent, respectively, from 2010 to 2021. Progress toward the elimination of mother-to-child HIV transmission has also continued in the Caribbean; more than 90 percent of pregnant women living with HIV knew their status in five of the nine countries in the region and were receiving ART.
Haiti and the Bahamas remain the worst affected, with an estimated national prevalence of 2.1 percent in Haiti and 3.3 percent in the Bahamas.
●Latin America – In the 17 countries comprising the Latin America region, an estimated 2.2 million adults and children are living with HIV; overall HIV prevalence is 0.4 percent [23,24]. Brazil, with its large population, accounts for 830,000 people living with HIV. In 2021, the number of new HIV infections was 110,000. New HIV infections have increased by 21 percent compared with those in 2010. However, AIDS-related deaths have decreased by 8 percent, and 60 percent of those with HIV are receiving ART.
The HIV epidemic is particularly pronounced among MSM throughout Latin America and in certain Caribbean countries. In particular, approximately 30 percent of MSM in Jamaica have HIV [23,24].
Asia and the Pacific — An estimated 6.0 million individuals with HIV (15 percent of the global total) live in Asia and the Pacific islands, which comprise 30 countries and 60 percent of the world's population [23,24]. With the exception of Thailand, where HIV prevalence is 1.1 percent, national HIV prevalence levels remain comparatively low (less than 1 percent) in most countries. Nevertheless, low prevalence in large populations can result in substantial HIV burdens. As an example, India's low national adult HIV prevalence rate of 0.2 percent translates into an estimated 2.4 million people living with HIV, one of the highest figures in the world.
In 2021, there were 260,000 new infections in this region, a decline of 14 percent from 2010; however, there was significant variation by country (eg, Thailand experienced a 50 percent decrease, while annual new infections increased in Pakistan and the Philippines by 39 and 141 percent) [23,24]. There has also been an overall 30 percent reduction in AIDS-related deaths since 2010, again with significant variation. Australia, Cambodia, and Thailand have achieved testing and treatment targets, but AIDS-related mortality rates are rising in Afghanistan, Pakistan, and the Philippines.
In China, the government estimates that 958,000 are infected with HIV, which represents an HIV prevalence of approximately 0.05 percent of the general population [23,24]. It was estimated that 131,000 new cases of HIV were diagnosed in China in 2019. Most cases are concentrated in five provinces: Guangdong, Guangxi, Xinjiang, Yunnan, and Henan, where residents became infected through contaminated equipment at a plasma donation center.
The estimates for India are based primarily on anonymous testing data from public clinics for prenatal care and for patients with other sexually transmitted infections (STIs) . Approximately 85 percent of HIV transmission in India is thought to be through sexual contact. Barriers to control of the epidemic include the lack of social acceptance of condoms and the legal ramifications of being gay that limit access and adherence to best prevention practices .
A high HIV prevalence has also been found among MSM in other Asian countries including Cambodia (9 percent), Thailand (15 percent), and India (18 percent) . Rising numbers of new infections among gay men and other MSM are a major concern. High prevalence among sex workers is also a major contributor to the spread of HIV in this region, where it exceeds 20 percent in certain urban centers throughout Asia (eg, Mumbai, Hanoi) [23,24].
Middle East and North Africa — The HIV epidemic in the Middle East and North Africa is growing. The estimated 14,000 new infections in 2021 represented a 33 percent increase since 2010 [23,24].
The epidemic in the region is highly concentrated among key populations and their sexual partners. People who inject drugs accounted for 43 percent of new HIV infections in 2021, and gay men and other MSM for another 23 percent . Combination prevention programs focusing on key populations need to expand, including HIV self-testing to increase coverage of pre-exposure prophylaxis and treatment. Women are particularly vulnerable to sex-based violence, stigma, and discrimination, resulting in limited access to HIV services. Coverage of services for the prevention of mother-to-child HIV transmission is among the lowest in the world.
United States — At the end of 2019, an estimated 1.2 million persons in the United States were living with HIV infection [35-37]. The national adult HIV prevalence was estimated to be about 0.3 percent. Of those with HIV, approximately 14 percent are not yet aware that they are infected. In 2019, there were an estimated 36,400 new HIV diagnoses in the United States, an overall 7-percent decrease compared with 2014, and more than a two-thirds reduction since the height of the epidemic in the mid-1980s . In 2018, there were 15,800 deaths among individuals diagnosed with HIV, a rate of 4.9 per 100,000 people.
HIV continues to have a disproportionate impact on certain populations. HIV prevention and treatment programs are not adequately reaching those who could most benefit from them, and certain groups such as MSM, transgender persons, Black Americans, and Hispanic/Latin Americans continue to be disproportionately affected. Black Americans and Hispanic/Latin Americans represented a higher proportion of people with HIV in 2019 than in 1981 . Additionally, the highest mortality rates among people with HIV are reported among Black Americans (accounting for 45 percent of all HIV-associated deaths, compared with 32 and 16 percent for White and Hispanic/Latin American populations, respectively).
MSM accounted for 69 percent of the new HIV diagnoses in the United States in 2018. Black American MSM accounted for 25 percent and Hispanic/Latin American MSM 20 percent of all new HIV diagnoses. From 2014 through 2018, the number of HIV diagnoses increased for transgender adults and adolescents. Among transgender male-to-female (MTF) adults and adolescents with new HIV diagnoses in 2018, those aged 25 to 29 years comprised the largest percentage (27 percent) followed by those aged 20 to 24 years (25 percent).
Straight people and people who inject drugs (PWID) also are affected by HIV in the United States. In 2018, 24 percent of HIV diagnoses were attributed to heterosexual contact. HIV diagnoses increased among PWID, with notable increases occurring among White PWID.
HIV diagnoses are not evenly distributed across states and regions. The highest rates of new diagnoses occur in the southern United States. More than 50 percent of new HIV diagnoses in 2018 occurred in 50 jurisdictions (48 counties, Washington, DC, and San Juan, Puerto Rico). These 50 jurisdictions, along with seven states with a disproportionate occurrence of HIV in rural areas, are prioritized in Phase I of a plan to eliminate new infections by 75 percent in 5 years and by 90 percent in 10 years, termed Ending the HIV Epidemic: A Plan for America ; the plan is based on the pillars of early diagnosis, rapid and effective treatment, multipronged prevention, and outbreak response.
Europe — By the end of 2021, there were 1.8 million HIV infections in the Eastern European and Central Asia Region, which includes the Russian Federation, where there is an urgent need to scale up HIV prevention services [23,40]. HIV prevalence averages 0.9 percent, but Eastern Europe and Central Asia are one of only three regions where the HIV epidemic is growing. In 2021, there were 160,000 new infections, an increase of 48 percent since 2010, and AIDS-related deaths increased 24 percent.
There is a large gap between HIV testing and treatment initiation, with only 63 percent of people with HIV who know their HIV status on treatment and only 41 percent [34 to 46 percent] of all people with HIV in the region virally suppressed. Key populations and their sexual partners are disproportionately impacted, accounting for 99 percent of new HIV infections in 2019. High levels of stigma and discrimination faced by lesbian, gay, bisexual, transgender, and intersex (LGBTI) people and people with HIV impede the provision of effective prevention services. High levels of physical, sexual, and emotional violence toward women and girls are also significant barriers.
The HIV epidemic in this region is strongly driven by heterosexual transmission and PWID, who accounted for 42 percent of all new infections in 2021, and is dominated by two countries, Russia and Ukraine (81 and 9 percent of new infections, respectively). The number of new HIV cases in Russia alone increased by 108 percent between 2010 and 2019. In Western and Central Europe, sexual transmission among MSM was the most common route, followed by heterosexual transmission.
Methods for establishing HIV incidence — Establishing accurate estimations of HIV incidence through the use of assays that can distinguish recent from chronic infection is critical to monitor the pandemic, identify target populations for interventions, reduce the risk of HIV transmission, and evaluate the effectiveness of HIV prevention and treatment programs. This is especially important in low- and middle-income countries that continue to bear a disproportionate share of the global burden of HIV/AIDS. In the United States, surveillance is based primarily on new HIV diagnoses, which does not distinguish whether the infection is new or just newly detected.
Determining the best strategy for measuring incidence is a challenge. Traditional HIV surveillance methods have used changes in prevalence to estimate HIV incidence rates, but this approach requires multiple rounds of surveillance over many years in the same population groups. Prospective follow-up of a cohort of people without HIV at baseline provides a direct measure of HIV incidence; however, such studies are challenging, expensive, not sustainable in resource-limited settings, and raise ethical issues. Furthermore, the enrollment of persons into a cohort study often leads to behavior changes that result in a lower observed HIV incidence than in the broader population of interest.
The United States Centers for Disease Control and Prevention (CDC) developed an innovative system designed to estimate the number of new HIV infections (or incidence, as opposed to new diagnoses) in a given year. This system estimates duration of infection based on results of the limiting antigen (LAg) HIV-1 capture enzyme immunoassay, which distinguishes recent infection (approximately 130 days after seroconversion) from chronic infection . The use of other tests (specifically an antibody avidity assay, HIV viral load measurement, and CD4 cell count) to supplement results from the LAg immunoassay in a multi-assay algorithm can more accurately detect recent infection. These tests are now being used in multiple countries for more accurate estimates of incidence.
MODES OF TRANSMISSION DRIVING THE PANDEMIC — The major modes of acquiring HIV infection are [42,43]:
●Parenteral transmission, predominantly among people who inject drugs (PWID)
The relative importance of these different modes of transmission in driving the HIV pandemic varies geographically and has evolved over time.
The risk of getting HIV varies widely depending on the type of exposure or behavior (such as sharing needles or having sex without a condom) (table 1). Some exposures to HIV carry a much higher risk of transmission than other exposures. For some exposures, while transmission is biologically possible, the risk is so low that it is not possible to put a precise number on it. However, risks add up over time so that even behavior with relatively small risk can accrue and lead to a high lifetime risk of HIV infection. There may be a relatively small chance of acquiring HIV when engaging in a risk behavior with an infected partner only once, but if repeated many times, the overall likelihood of becoming infected is much higher.
Sexual transmission — More than 80 percent of infections worldwide occur through heterosexual transmission, and over 50 percent of all people with HIV in the world are female . These statistics reflect the situation in sub-Saharan Africa, which houses the majority of the world's population with HIV and where heterosexual transmission is the main contributor to the HIV pandemic.
In contrast, more males than females are infected with HIV in other parts of the world. This, in part, reflects the epidemic among men who have sex with men (MSM), who are 19 times more likely than the general population to have HIV . In some resource-rich settings, despite high rates of testing and access to antiretroviral therapy (ART), the incidence of HIV infection among MSM has increased while the incidence from other modes of transmission have trended downwards. As an example, in the United States, the number of newly diagnosed HIV infections attributed to MSM sexual contact increased from 2009 to 2018, while those attributed to injection drug use and heterosexual contact decreased . At the end of 2018, MSM transmission accounted for 69 percent of newly diagnosed HIV infections in the United States.
Injection drug use — Outside of sub-Saharan Africa, injection drug use (IDU) accounts for approximately 30 percent of new HIV infections . IDU is fueling HIV epidemics in Central and Eastern Europe and in some countries of Asia . It is also a major concern in industrialized nations and the Middle East. The vulnerability of this risk group and the rapidity with which HIV can spread through needle-sharing were reflected by a 2015 outbreak of HIV among people who inject drugs (PWID) in a rural region of Indiana, where HIV had previously been only rarely reported . Decades of experience within dozens of countries supports the effectiveness of needle exchange programs, in which PWID can trade in used needles for clean ones [49,50]. Across eight countries in Eastern Europe and Central Asia, a tripling of needle exchange program coverage between 2005 and 2010 was associated with reduced injecting risk behavior and reduced new HIV and hepatitis C virus infections. After 10 years of needle exchange programs in Australia, the number of new HIV infections was reduced by up to 70 percent. Unfortunately, 43 percent of countries with documented IDU do not have needle-syringe programs in place.
A meta-analysis in 2008 examined the role of IDU as a cause of HIV transmission worldwide . Prevalence estimates of IDU could be ascertained for 61 countries containing an estimated 77 percent of the world's population. Estimates suggest that 15.9 million people might inject drugs worldwide; the largest numbers of injectors were found in China, the United States, and Russia, where mid-estimates of HIV prevalence among injectors were 12, 16, and 37 percent, respectively. Furthermore, HIV prevalence among PWID was 20 to 40 percent in five countries and over 40 percent in nine.
Mother-to-child transmission — Over two million infants are born to women with HIV annually. These children are vulnerable to HIV transmission in utero, at birth, or through breastmilk. Mother-to-child transmission accounts for 90 percent of HIV infections among children worldwide. In the most affected countries in the world, such as in sub-Saharan Africa, 20 to 40 percent of pregnant women have HIV, and one-third of their babies can become infected if they are not on ART . Antiretroviral use during pregnancy, at the time of delivery, and during breastfeeding can nearly eliminate transmission, and, over the past several years, there has been a rapid scale-up of services to prevent mother-to-child transmission of HIV. This has reduced the annual number of new infections among children by 50 percent worldwide since 2010. Globally in 2021, an estimated 85 percent of pregnant or breastfeeding women living with HIV were receiving antiretroviral medicines to prevent transmission of HIV to their children, up from 50 percent in 2010.
Nevertheless, there were 1.7 million children under 15 years of age living with HIV worldwide in 2021 [23,24]. An additional 160,000 children acquired HIV in 2021 (2800 per week), and 95,000 children died of AIDS-related causes (260 per day). In some high-burden countries, such as Angola, Chad, and Nigeria, less than half of the pregnant or breastfeeding women living with HIV are receiving antiretroviral medicines.
The risk of perinatal transmission and the effect of antiretroviral use on that risk are discussed in detail elsewhere. (See "Prevention of vertical HIV transmission in resource-limited settings" and "Prevention of HIV transmission during breastfeeding in resource-limited settings" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings".)
RISK FACTORS — Risk of HIV transmission varies by the viral level of the source individual, the mode of transmission, and other cofactors. As an example, the risk of sexual transmission of HIV is also impacted by the type of sexual behavior and the presence of concomitant sexually transmitted infections (STIs). Risk factors for transmission and strategies to reduce risk are discussed in detail elsewhere. (See "HIV infection: Risk factors and prevention strategies", section on 'Risk factors for infection'.)
ART AND HIV EPIDEMIOLOGY
Impact of ART — The introduction of antiretroviral therapy (ART) has substantially impacted the epidemiology of HIV. Overall, HIV prevalence has increased, likely because of improved survival among those who are treated, and incidence has decreased, likely as a result of decreased transmission with more widespread treatment. (See 'General statistics' above.)
The improvements in AIDS- and non-AIDS-related morbidity and mortality among individuals with HIV who are successfully treated with ART are discussed in detail elsewhere. (See "When to initiate antiretroviral therapy in persons with HIV", section on 'Universal treatment'.)
ART coverage — Improving delivery of antiretroviral therapy (ART) in resource-limited countries has been a primary focus of international efforts to combat the HIV pandemic.
By the end of 2021, ART coverage globally had reached approximately 28.7 million people, compared with 7.5 million in 2010 [23,24,52]. By this time, over USD $18 billion had been allocated for ART care and prevention, mostly in resource-limited countries. One analysis demonstrated that HIV funding was associated with a decline in all-cause mortality rates in the African countries where it had provided the greatest ART coverage . The development of generic medications has also been an important advance in making ART available in resource-limited countries . In December 2013, the UNAIDS Programme Coordinating Board called on UNAIDS to support country- and region-led efforts to establish new targets for HIV treatment scale-up beyond 2015. In response, stakeholder consultations on new targets have been held in all regions of the world. These targets by 2020 were:
●90 percent of all people living with HIV will know their HIV status.
●90 percent of all people with diagnosed HIV infection will receive sustained ART.
●90 percent of all people receiving ART will have viral suppression.
However, new targets have been set for 2030 as follows:
●95 percent of all people living with HIV will know their HIV status.
●95 percent of all people with diagnosed HIV infection will receive sustained ART.
●95 percent of all people receiving ART will have viral suppression.
With international support, several resource-limited countries have been able to successfully provide widespread ART access. In Zambia, Rwanda, Botswana, and other countries, HIV treatment coverage either doubled or almost doubled from 2015 to 2021 , reinforcing the feasibility of rapid scale-up. Especially encouraging is the rapid expansion of treatment services in certain fragile settings, such as the Democratic Republic of the Congo, where the proportion of people living with HIV receiving HIV treatment also doubled from 16 to 33 percent between 2012 and 2015. These encouraging results from diverse countries provide credibility to the attainment of the 90-90-90 targets. However, challenges remain, and many countries are struggling to achieve the third 90 percent target . In 2021, of the 38.4 million people with HIV worldwide, 84 percent knew their HIV status, 75 percent were on ART, and 66 percent were HIV virally suppressed . The progress in children (ages <15 years) is slower, with only 40 percent virally suppressed.
Access to ART — Despite advances in antiretroviral therapy (ART) provision, a large proportion of people with HIV do not have access to or are otherwise not receiving ART .
Late access to ART has been associated with high early mortality rates . In the Zambia study, most mortality occurred within the first three months of starting therapy, consistent with the advanced stage of disease at presentation (mean CD4 cell count 143 cells/microL) . In another community-based antiretroviral treatment program among 1340 patients with HIV in South Africa, more than 46 percent of the total mortality occurred after enrollment, but prior to the initiation of ART .
Reasons for suboptimal ART use despite availability include failure to test and diagnose HIV, failure to link and retain in care, stigma and misperceptions about HIV and its risks, and poor coordination of services. Even transportation costs can be a major barrier for patients trying to access ART. One study in Uganda demonstrated that home-based care can be less costly and as efficacious as clinic-based care in attaining viral suppression .
COINFECTIONS WITH HIV — The epidemiology of HIV is intertwined with those of numerous other infectious disorders because of geographic overlap and the adverse impact of HIV-associated immunosuppression with the natural history of such infections. In turn, these infections contribute to the excess morbidity and mortality associated with HIV infection. Such infections include tuberculosis, malaria, cryptococcal meningitis, and chronic viral hepatitides. These are discussed in detail elsewhere:
●HIV infection in humans likely originated from zoonotic transmission from nonhuman primates. HIV-1 and HIV-2 are the two types of HIV identified worldwide. HIV-1 is the more prominent type and consists of four distinct viral groups; group M is the most common and has worldwide distribution. Viruses from group M are divided into nine distinct subtypes and recombinants of the subtypes, which have varying geographic distribution (figure 1). (See 'Origin of the HIV pandemic' above.)
●In its fourth decade, the HIV pandemic has reached every country and nearly all populations throughout the world. The overall prevalence of HIV continues to increase in some countries with improved survival with antiretroviral treatment, but the incidence of new HIV infections has declined since the year 2000. (See 'Worldwide statistics' above.)
●Nearly two-thirds of the world's population with HIV is in sub-Saharan Africa, where heterosexual transmission is the main contributor to the HIV epidemic. Elsewhere, other modes of infection are more important. Injection drug use is fueling HIV epidemics in Central and Eastern Europe and in some countries of Asia. In some resource-rich settings, including the United States, the incidence of HIV infection has been increasing among men who have sex with men despite general trends of decreasing incidence otherwise. (See 'Modes of transmission driving the pandemic' above.)
●Marked advances in HIV antiretroviral therapy (ART) have resulted in significant changes in the survival rate and quality of life of individuals with HIV. Improving delivery of ART in resource-limited countries has been a primary focus of international efforts to combat the HIV pandemic. Despite advances in ART provision in such settings, a large proportion of patients with HIV still do not have access to or are otherwise not receiving ART. (See 'ART and HIV epidemiology' above.)
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