Epidemiology of HIV and AIDS

The human immunodeficiency virus (HIV) kills or impairs the cells of the immune system and progressively destroys the body’s ability to protect itself. Over time, a person with a deficient immune system (immunodeficiency) may become vulnerable to infections by disease-causing organisms such as bacteria or viruses. These infections can become life threatening.

Mechanism of HIV Infection

HIV enters the bloodstream and seeks out T-helper lymphocytes, white blood cells essential to the functioning of the immune system. One of the functions of these cells is to regulate the immune response in the event of attack from disease-causing organisms such as bacteria or viruses. When the virus infects the T-helper lymphocyte, the cell sends signals to other cells, which produce antibodies. This T-helper lymphocyte cell may also be called the T4 or the CD4 cell.

HIV infects and destroys the T-helper lymphocytes and damages their ability to signal for antibody production. This results in the eventual decline of the immune system.

There are five stages of HIV/AIDS infection:

·         Primary or acute infection

·         The window period ending with seroconversion

·         The asymptomatic period

·         The period of being symptomatic

·         Full-blown AIDS

 The Origin of HIV

Since the human immunodeficiency virus was identified in 1983, researchers have worked to pinpoint the origin of the virus. In 1999 an international team of researchers reported that they discovered the origins of HIV-1, the predominant strain of HIV in the developed world.

A subspecies of chimpanzees native to West Equatorial Africa was identified as the original source of the virus. The researchers believe that HIV-1 was introduced into the human population when hunters became exposed to infected blood. The transmission of HIV is driven by changes in migration, housing, travel, sexual practices, drug use, war, and economics that affect both Africa and the entire world.

HIV Strains and Subtypes

HIV has divided into two primary strains: HIV-1 and HIV-2. Worldwide, the predominant virus is HIV-1, and generally when people refer to HIV without specifying the type of virus they are referring to HIV-1. The relatively uncommon HIV-2 type is concentrated in West Africa and is rarely found elsewhere.

HIV is a highly variable virus that mutates very readily. This means there are many different strains of HIV, even within the body of a single infected person. Based on genetic similarities, the numerous virus strains may be classified into types, groups, and subtypes.

Both HIV-1 and HIV-2 have several subtypes. It is virtually certain that more undiscovered subtypes are in existence now. It is also probable that more HIV subtypes will evolve in the future. As of 2001, blood testing in the United States can detect both strains and all known subtypes of HIV.

Epidemiology of HIV and AIDS

Epidemiology is the study of how disease is distributed in populations and of the factors that influence or determine this distribution. Epidemiologists try to discover why a disease develops in some people and not in others. Clinically, AIDS was first recognized in the United States in 1981. In Washington State, the first case of AIDS also appeared in 1981. But it wasn't until 1983 that the virus was identified as the cause of the new disease. Since then, the number of AIDS cases has continued to increase, both in the United States and in other countries. 

People who are infected with HIV come from all races, countries, sexual orientations, genders, and income levels. Globally, most of the people who are infected with HIV have not been tested and are unaware that they are living with the virus. The U.S. Centers for Disease Control and Prevention (CDC) estimates that 1.2 million people aged 13 years and older are living with HIV infection, including 168,000 (14%) who are unaware of their infection. This is a decline from 25% in 2003 and 20% in 2012 and is a positive sign because studies have shown that many people with HIV who know that they are infected avoid behaviours that spread infection to others, and they can get medical care and take antiviral medications that may reduce HIV spread by as much as 96% (CDC, 2014; 2014b).

CDC estimates that that there are only 4 transmissions per year for every 100 people living with HIV in the United States, which means that the clear majority (at least 95%) of people living with HIV do not transmit the virus to anyone else. This represents an 89% decline in the transmission rate since the mid-1980s, reflecting the combined impact of testing, prevention counselling, and treatment efforts targeted to those living with HIV infection (UNAIDS, 2013).

The estimated incidence of HIV has remained stable overall in recent years, at about 50,000 new HIV infections per year (CDC, 2014b). While this is still too high a level, stabilization is a sign of progress. With continued increases in the number of people living with HIV thanks to effective HIV medications, there are more opportunities for HIV transmission than ever before. Yet, the annual number of new infections has not increased (UNAIDS, 2013).

Worldwide, there were about 2.1 million new cases of HIV in 2013, and about 35 million people are living with HIV around the world. Of those, 3.2 million are children, 2.1 million are adolescents, and 4.2 million are people over age 50. In 2013 new HIV infections worldwide were 2.1 million, but new infections have fallen 38% since 2001 and new infections among children have fallen by 58% in the same period (CDC, 2014a; UNAIDS, 2014).

Through 2011 the cumulative estimated number of deaths of people with diagnosed HIV infection ever classified as stage 3 (AIDS) in the United States was 648,459 (deaths may be due to any cause, which can make data interpretation complex). Nearly 39 million people with AIDS have died worldwide since the epidemic began (CDC, 2014a).

Globally, AIDS-related deaths, which peaked in 2005 at 2.4 million, have declined steadily ever since, and were estimated at 1.5 million in 2013 (UNAIDS, 2014). Even though Sub-Saharan Africa bears the biggest burden of HIV/AIDS, countries in South and Southeast Asia, Eastern Europe and Central Asia, and those in Latin America are significantly affected by HIV and AIDS (CDC, 2014a; UNAIDS, 2014).

The discovery of combination antiviral drug therapies in 1996 resulted in a dramatic decrease in the number of deaths due to AIDS among people given the drug therapies. Many people who have access to the therapies may not benefit from them or may not be able to tolerate the side effects. The medications are expensive and require strict dosing schedules. In developing countries many people with HIV have no access to the newer drug therapies.

During the period 2008–2013, men accounted for 85% of the new cases and women for 15%. Fifty-seven percent were white, 17% black, 16% Hispanic, and 5% Asian. The remaining 5% included native Hawaiians, American Indians, and those of multiple race. Children under 13 accounted for 2% of the new cases, while those age 13 to 24 were another 14%. Most of the cases (57%) were among adults 35 to 54, and the remaining 28% were age 54 and older (WDOH, 2014).

Source: https://www.atrainceu.com/course-module-short-view/2493557-136_washington-hiv-aids-4-units-module-01

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HIV Elite Controllers and Prospect of HIV Vaccine

If left untreated, HIV will typically progress to AIDS; that is the general rule. However, a small subset of HIV-positive people is believed to be able to control HIV without ever progressing to AIDS—and without the use of antiretroviral drugs. These people, once called long-term non-progressors, are today commonly referred to as HIV elite controllers.

While experts had long considered this level of innate resistance a mystery, the bulk of evidence today suggests that specific genetic mutations confer to this "elite" control of HIV. As such, greater focus is being placed on determining if the same mechanisms can be mimicked in other people, with the aim of designing an AIDS vaccine or some immunologic approach to controlling HIV drug without the use of drugs.

Elite Controllers

Elite controllers are broadly defined as HIV-positive people who maintain an undetectable HIV viral loads without the use of HIV drugs. Relieved of the burden of uncontrolled viral activity, elite controllers typically have well-preserved immune systems (as measured by the CD4 count), meaning their risk of opportunistic infection is considered low.

It is estimated that elite controllers account for about 1 in 300 HIV-infected people. That figure can vary, however, given that research often defines elite controllers differently.

In some cases, elite controllers are defined as being able to maintain undetectable virus for a year; others are only included after anywhere from 3-15 years.

This is an important distinction because we cannot confidently say those elite controllers will never advance in their disease or experience a sudden activation of viral activity.

We must assume that some of this population will.

Mechanism of Elite Control

Early studies were not successful in finding common traits and characteristics among elite controllers. It was not until the advent of genetic research and technologies that we were able to pinpoint commonalities among those with presumed elite control.

Among the key researchers, Harvard Medical School scientist Bruce Walker, M.D. was among the first to isolate the genetic differences in the make-up of this population, drawing evidence from a cohort of 1,100 elite controllers and 800 people with AIDS.

In the normal immune system, specialized immune cells, called "helper" T-cells, recognize disease-causing viruses and "tag" them for neutralization. "Killer" T-cells then lock onto the virus at specific attachment points and effectively kill the virus from within. 

However, HIV can adapt to the immune onslaught, mutating to prevent the "killer" cell attachment, while destroying the "helper" cells needed to signal the attack in the first place.

In his group's research, Walker was able to determine that the "killer" T-cells in the elite control group were able to function independently of "helper" T-cells.

Furthermore, his team found that the "killer" cells were able to neutralize a broad diversity of HIV, not just a specific subset as is most often the case.

Since Walker's research was published, scientists have been able to isolate many of the genetic mutations found in the genome of the elite control population. Among them:

• The mutation of the FUT2 gene, which is found in 20% of the European population and is known to provide strong resistance to other types of virus.
• The presence of specialized genes called human leukocyte antigen B (HLA-B), which are found in a large proportion of elite controllers.

The genetic mechanism which allows elite controllers to produce so-called broadly neutralizing antibodies (bNAbs) faster than non-elite controllers. bNAbs, by definition, can kill a broader variety of HIV. Typically, a non-elite-controller can take years to produce these cells, by which time HIV has already establish hidden latent reservoirs which are largely impenetrable to attack. Elite controllers, by contrast, seem to be able to activate bNAbs almost immediately, preventing (or at least reducing) the establishment of latent reservoirs.

By identifying these genetic mechanisms, scientists hope to replicate the processes either through gene therapy, an immunologic vaccine, or a combination of biomedical approaches.

Downside to Elite Control

Despite the optimism surrounding elite control and associated vaccine research, increasing evidence has shown that elite control comes at a price. When compared to non-elite-controllers on antiretroviral therapy (ART), elite controllers tend to have more than twice the number of hospitalizations, particularly from non-HIV-associated diseases that are known to disproportionately affect all people with HIV. 

When compared to non-elite-controllers on ART with undetectable viral loads, elite controllers had 77% more hospitalizations. Even non-elite-controllers with detectable virus fared better, suggesting that ART manages to minimize some of the long-term chronic inflammation that we know can increase the risk and premature development of non-HIV-associated cancers, cardiovascular diseases, and neurological disorders.

Source: https://www.verywellhealth.com/hiv-elite-controllers-48616

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