|Year : 2016 | Volume
| Issue : 1 | Page : 59-63
Global scenario of HIV/AIDS: Declining trend and moving toward cure
Ramalingam Sekar1, Manoharan Mythreyee2
1 Assistant Professor, Department of Microbiology, Government Theni Medical College, Tamil Nadu Dr. MGR Medical University, Theni, Tamil Nadu, India
2 Professor, Department of Microbiology, Government Theni Medical College, Tamil Nadu Dr. MGR Medical University, Theni, Tamil Nadu, India
|Date of Web Publication||23-Feb-2016|
Department of Microbiology, Government Theni Medical College, Theni - 625 512, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
People living with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) (PLH/PLHA) are increasing worldwide (29.8 million in 2001 and 36.9 million in 2014) mainly owing to the aversion of AIDS related deaths by effective antiretroviral therapy (ART). Although the prevalence is increasing, the new HIV infections decreased from 3.4 million in 2001 to 2 million in 2014, and AIDS-related deaths were decreased from the peak of 2.4 million in 2005 to 1.2 million in 2014. Implementation of ART with wide coverage and free access, especially in low- and middle-income countries is an important reason for the decline of AIDS-related deaths. Further, it is expected that the recent understanding in the mechanisms of latent infection and importance of reservoir could help to achieve a "functional cure" from HIV infection in near future.
Keywords: Acquired Immune Deficiency Syndrome (AIDS)-related mortality, Human Immunodeficiency Virus (HIV)/AIDS, HIV cure, incidence, prevalence
|How to cite this article:|
Sekar R, Mythreyee M. Global scenario of HIV/AIDS: Declining trend and moving toward cure. Indian J Public Health 2016;60:59-63
|How to cite this URL:|
Sekar R, Mythreyee M. Global scenario of HIV/AIDS: Declining trend and moving toward cure. Indian J Public Health [serial online] 2016 [cited 2020 Jul 6];60:59-63. Available from: http://www.ijph.in/text.asp?2016/60/1/59/177310
| Introduction|| |
After three decades of intensive research on Human Immunodeficiency Virus (HIV), it remains as an important public health challenge worldwide, with significant social and economic implications.  However, advances in the treatment of HIV infection have resulted in an ultimate shift in its epidemiology, from a deadly infectious disease to a chronic manageable condition.  Thus, the rate of incidence of Acquired Immune Deficiency Syndrome (AIDS) that is the most severe clinical presentation of HIV infection have declined compared to that in 1990s. 
In the year 2000, the Millennium Declaration Goal was established with special attention to control the global burden of HIV/AIDS by 2015 (MDG 6). After the declaration, enormous fund was released for the control of HIV infection, with the changing priority from time to time. Initially, the priority was given for primary prevention (prevention of HIV acquisition), and later for secondary prevention (prevention of HIV transmission), and recently the priority was shifted to the management of PLH/PLHA. Reportedly, from 2000 to 2014, about US$185.8 billion has been spent for the public health measures of HIV infection.  As we have reached the year 2015, herewith we analyze the trend of HIV prevalence and incidence along with AIDS-related deaths, and therapeutic/preventive milestones achieved in HIV research since 2001.
| Global Scenario of HIV/AIDS: Current Picture|| |
Prevalence: People living with HIV
The global prevalence of HIV was gradually increased from 29.8 million in 2001 to 36.9 million in 2014 [Figure 1]. The increase in HIV prevalence is mainly attributed to two factors - first, the HIV causes persistent infection till death as it creates permanent reservoir in memory T H cells, and the second factor is the availability of antiretroviral therapy (ART) that significantly improves the lifespan of PLH. Further, the occurrence of new HIV infections add up to the existing cases increases the PLH throughout the globe. Although the PLH are distributed worldwide, major proportion of them were living in the developing countries located in the southern Africa and Asia [Figure 2].
|Figure 1: Global estimate of PLHA and estimated AIDS-related deaths from 2001 to 2014|
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|Figure 2: Estimated PLHA in 2015 and trends in the incidence of new infections from 2001 to 2014 in different UNAIDS regions|
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Incidence: New HIV infections
The number of people who are newly infected with HIV is constantly declining in most parts of the world [Figure 3]. According to the United Nations Programme on HIV and AIDS (UNAIDS),  about 2 million new HIV infections were documented in the year 2014, which is about 41.2% decline from the year 2001 (3.4 million). More specifically, in the past 4 years alone, new HIV infections declined by 16.7% (2.4 million in 2011) and it suggests that the current control measures implemented by public health authorities were working well and intensifying the control programs would give us better results.
Over the past decade, control of HIV incidence among children has been dramatic. In spite of having stringent preventive measures, about 0.22 million children were newly infected with HIV in the year 2014. However, this is 62.1% lower than the HIV incidence among children from the year 2001 (0.58 million). Similarly, 37.9% decrease was observed among adults (from 2.9 million in 2001 to 1.8 million in 2014).
It is obvious that the stringent efforts taken by the UNAIDS is responsible for the decline in new HIV infections in many parts of the world including sub-Saharan Africa  and Asia , [Figure 2] and [Figure 3]. However, the risk of second growth phase of the epidemic should always be kept in mind.  Hence, the intensified prevention efforts need to be continued as long as HIV is not completely eliminated from the world.
| AIDS-Related Deaths|| |
Global AIDS-related deaths were peaked at 2.4 million in 2005 and decreased to 1.2 million in 2014 (40% decline) [Figure 1]. It is well known that the AIDS-related deaths were primarily caused by opportunistic infections, which takes an opportunity of immunocompromised condition (caused by HIV infection) to infect the host, leading to fatal AIDS defining illnesses. But, in recent years, AIDS-related mortality was significantly reduced, owing to an effective ART. Importantly, about 50% of all deaths among the PLH who have started ART are not due to AIDS.  However, tuberculosis, an AIDS defining illness, continues to be a major cause of morbidity and mortality in low- and middle-income countries. Nevertheless, the HIV-related tuberculosis mortality is 33% declined since 2004. ,
| Management of HIV/AIDS: Highly Active Antiretroviral Therapy|| |
A combination of antiretroviral regimens was developed in the late-1990s and introduced for clinical practice in the year 1997, which transformed HIV from a progressive fatal disease to a chronic manageable disease.  ART not only prevents AIDS-related illness and death, it also has the potential to significantly reduce the risk of HIV transmission and the spread of tuberculosis.  From 1995 to 2013, ART had averted about 7.6 million AIDS-related deaths worldwide, including 4.8 million deaths in sub-Saharan Africa. 
The management of HIV has now become simpler and cheaper than ever before, because of the increased access and wide availability of low-cost generic drugs and fixed dose combinations of drugs. Based on the evidence, that the early initiation of ART provides better life to PLH, the World Health Organization guidelines  for ART initiation has been revised recently. The early initiation of ART decreases the risk of opportunistic infections as the immune system is not allowed to get compromised, thus causing a paradigm shift in the management of HIV from restoration of CD4 cells to preservation of CD4 cells. For this reason, the "test and treat strategy" has been adopted by many clinicians  in developed countries and it could become a worldwide norm for HIV management in the near future.
Because of the success of ART in attaining viral suppression, life expectancy of these patients has now become like a normal person.  However, toxic effects associated with the long-term use of ART causes premature ageing,  consequently many age-related issues were reported in this population. Therefore, future AIDS control programs should address these issues to make an effective public health policy.
| Functional Cure for HIV: Not Far Away|| |
Despite the great successes of ART in reducing AIDS-related morbidity and mortality, it is unable to cure HIV and it necessitates lifelong therapy.  The major limitations of ART is its inability to act on viral reservoirs and latently infected cells. Hence, the current theme of HIV research is mainly focused on finding ways for HIV cure to avoid drug toxicities and economic burden associated with lifelong ART.
A mechanism of HIV control similar to long-term nonprogressors (LTNP) has been observed among the HIV infected persons who had initiated ART during the acute phase of HIV infection. Interestingly, they had retained the HIV control for more than 10 years even after the discontinuation of ART at 3 years.  This observation suggests that early and prolonged ART might help some people to achieve a permanent control of viral replication without complete eradication called "functional cure" from HIV infection. Additional observations on the same mechanism of functional cure have been reported among HIV-infected infants. ,, However, another report states that the discontinuation of ART causes the rebound of viral load in an infant.  Hence, further research is needed to evaluate the efficacy of the early initiation of ART in achieving functional cure from HIV infection.
Another approach was attempted to manually reactivate all latent viruses in the body, thus clearing the viral reservoir  and providing a functional cure. Although the study observed increased activation of latent virus, it does not document any reduction in viral reservoir. Hence, this approach is still in the preliminary stage of achieving a functional cure.
The Berlin patient case report is little more interesting and it is the first documented report on HIV cure in medical literature.  The patient had received stem cell transplantation from a donor carrying a protective C-C chemokine receptor type 5 (CCR5) (co-receptor for HIV infection) mutation for the treatment of leukemia. Although his ART was stopped, there is no viral RNA detected in his plasma or tissue for more than 6 years. , This case led to the process of developing a gene therapy to eliminate CCR5 in patient derived CD4 cells. 
It is expected that the recent understanding in the mechanisms of latent infection  and importance of reservoir  might help to find a way for "therapeutic cure"  or at least a "functional cure" from HIV infection in near future. ,
| Conclusion|| |
HIV infection still continues to be a major contributor to the global burden of disease, especially in sub-Saharan Africa. The incidence of HIV infections has been clearly documented to be declining across the globe. Further, ART has increased the lifespan of PLH and averted many AIDS-related deaths, and contributing to increase in the global prevalence of PLH. Recent understanding in the mechanisms of HIV infection might help to find a way for therapeutic cure or at least a functional cure from HIV infection in near future.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, et al
. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384:1005-70.
Kayeyi N, Fylkesnes K, Michelo C, Makasa M, Sandøy I. Decline in HIV prevalence among young women in Zambia: National-level estimates of trends mask geographical and socio-demographic differences. PLoS One 2012;7:e33652.
Sekar R, Amudhan M, Sivashankar M, Veeran R, Jayachandran C, Mythreyee M. Declining trend of HIV infection among the rural population of South India - A comparison of HIV prevalence in high risk and low risk groups. J Infect 2011;63:91-2.
Sekar R, Amudhan M, Sivashankar M, Mythreyee M. Recent trends in HIV prevalence in a remote setting of southern India: Insights into arranging HIV control policies. J Infect Dev Ctries 2013;7:838-43.
Maartens G, Celum C, Lewin SR. HIV infection: Epidemiology, pathogenesis, treatment, and prevention. Lancet 2014;384:258-71.
Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet 2013;382:1525-33.
Tanser F, Barnighausen T, Grapsa E, Zaidi J, Newell ML. High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science 2013;339:966-71.
Maek-a-nantawat W, Phanuphak N, Teeratakulpisarn N, Pakam C, Kanteeranon T, Chaiya O, et al
. Attitudes toward, and interest in, the test-and-treat strategy for HIV prevention among Thai men who have sex with men. AIDS Care 2014;26:1298-302.
May MT, Gompels M, Delpech V, Porter K, Orkin C, Kegg S, et al
.; UK Collaborative HIV Cohort (UK CHIC) Study. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS 2014;28:1193-202.
Fisher M, Cooper V. HIV and ageing: Premature ageing or premature conclusions? Curr Opin Infect Dis 2012;25:1-3.
Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, et al
.; ANRS VISCONTIStudy Group. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog 2013;9:e1003211.
Bitnun A, Samson L, Chun TW, Kakkar F, Brophy J, Murray D, et al
. Early initiation of combination antiretroviral therapy in HIV-1-infected newborns can achieve sustained virologic suppression with low frequency of CD4+ T cells carrying HIV in peripheral blood. Clin Infect Dis 2014;59:1012-9.
Shiau S, Kuhn L. Antiretroviral treatment in HIV-infected infants and young children: Novel issues raised by the Mississippi baby. Expert Rev Anti Infect Ther 2014;12: 307-18.
Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M Jr, Chun TW, et al
. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med 2013;369:1828-35.
Butler KM, Gavin P, Coughlan S, Rochford A, Donagh SM, Cunningham O, et al
. Rapid viral rebound after 4 years of suppressive therapy in a seronegative HIV-1 infected infant treated from birth. Pediatr Infect Dis J 2014. [Epub ahead of print].
Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, et al
. Depletion of latent HIV-1 infection in vivo
: A proof-of-concept study. Lancet 2005;366:549-55.
Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, et al
. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009;360:692-8.
Yukl SA, Boritz E, Busch M, Bentsen C, Chun TW, Douek D, et al
. Challenges in detecting HIV persistence during potentially curative interventions: A study of the Berlin patient. PLoS Pathog 2013;9:e1003347.
Li L, Krymskaya L, Wang J, Henley J, Rao A, Cao LF, et al
. Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol Ther 2013;21:1259-69.
Kumar A, Abbas W, Herbein G. HIV-1 latency in monocytes/macrophages. Viruses 2014;6:1837-60.
Svicher V, Ceccherini-Silberstein F, Antinori A, Aquaro S, Perno CF. Understanding HIV compartments and reservoirs. Curr HIV/AIDS Rep 2014;11:186-94.
Lewin SR, Deeks SG, Barré-Sinoussi F. Towards a cure for HIV - are we making progress? Lancet 2014;384:209-11.
Barré-Sinoussi F, Ross AL, Delfraissy JF. Past, present and future: 30 years of HIV research. Nat Rev Microbiol 2013;11:877-83.
Deeks SG, Autran B, Berkhout B, Benkirane M, Cairns S, Chun TW, et al
.; International AIDS Society Scientific Working Group on HIV Cure. Towards an HIV cure: A global scientific strategy. Nat Rev Immunol 2012;12:607-14.
[Figure 1], [Figure 2], [Figure 3]