World AIDS day : Better to Know More

Author : Himanshu Sadulwad

Synopsis

An estimated 37.7 million people are currently living with HIV. As of now, it has claimed 36.3 million lives. A disease with one of the highest death tolls in the world, we speak of none other than HIV-AIDS.

AIDS remains a major public health issue that affects millions worldwide. On this World AIDS day, let us educate ourselves a bit more on this crucial topic.

Origin

In humans, AIDS is caused by two lentiviruses namely, Human Immunodeficiency Viruses types 1 and 2 (HIV-1 and HIV-2). In this section, we describe the origins of these viruses and the circumstances that lead to the AIDS pandemic.

Both HIVs are the result of multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) naturally infecting African primates. Most of these transfers resulted in viruses that spread in humans to only a limited extent. However, one transmission event, involving SIVcpz from chimpanzees in southeastern Cameroon gave rise to HIV-1 group M which is the principal cause of the AIDS pandemic ( Paul Sharp and Beatrice Hahn 2011).

How humans acquired the ape precursors of HIV-1 groups M, N, O, and P is not known; however, based on the biology of these viruses, the transmission must have occurred through cutaneous or mucous membrane exposure to infected ape blood or body fluids. Such exposures occur most commonly in the context of bushmeat hunting (Peeters et. al. 2002). Whatever the circumstances it seems clear that human-ape encounters in west-central Africa have resulted in four independent cross-species transmission events.

Since its first discovery, HIV-2 has remained largely restricted to West Africa, with the highest prevalence rates in Guinea-Bissau and Senegal ( de Silva et al. 2008). Most individuals infected with HIV-2 do not progress to AIDS, although those who do, show clinical symptoms indistinguishable from HIV-1 ( Rowland-Jones and Whittle 2007).

A sooty mangabey origin of HIV-2 was first proposed in 1989 (Hirsch et al. 1989) and subsequently confirmed by demonstrating that humans in West Africa harbored HIV-2 strains that resembled locally circulating SIVsmm infections (Gao et al. 1992; Chen et al. 1996). The fact that sooty mangabeys are frequently hunted as agricultural pests in many areas of West Africa provided plausible routes of transmission.

Virology

The human immunodeficiency virus (HIV) is grouped to the genus Lentivirus within the family of Retroviridae. On the basis of genetic characteristics and differences in the viral antigens, HIV is classified into the types 1 and 2 (HIV-1, HIV-2). Epidemiologic and phylogenetic analyses currently available imply that HIV was introduced into the human population around 1920 to 1940.

HIV Genome structure

The HIV genome consists of two identical single-stranded RNA molecules that are enclosed within the core of the virus particle. The genome of the HIV provirus, also known as proviral DNA, is generated by the reverse transcription of the viral RNA genome into DNA, degradation of the RNA and integration of the double-stranded HIV DNA into the human genome. The DNA genome is flanked at both ends by LTR (long terminal repeat) sequences.

In the direction 5′ to 3′ the reading frame of the gag gene follows, encoding the proteins of the outer core membrane, the capsid protein, the nucleocapsid and a smaller, nucleic acid-stabilising protein.The gag reading frame is followed by the pol reading frame coding for the enzymes protease, reverse transcriptase, RNase H and integrase . Adjacent to the pol gene, the env reading frame follows from which the two envelope glycoproteins gp120 (surface protein) and gp41 (transmembrane protein) are derived.

Particle structure

The mature HIV particle is round, measures approximately 100 nm in diameter, with an outer lipid membrane as its envelope.The viral envelope is composed of a lipid bi-layer and, in mature virus particles, the envelope proteins SU and TM. The conical capsid is assembled from the inner capsid protein p24.Two identical molecules of viral genomic RNA are located inside the capsid and several molecules of the viral enzymes RT/RNase H are bound to the nucleic acid.

Infection of human cells

The surface glycoprotein gp120 of the mature HIV particle binds to the CD4 receptor on the host cell. All CD4-positive cells such as T helper cells, macrophages, dendritic cells and astrocytes are susceptible to HIV. After attachment to the CD4 molecule via the C4-domain of gp120, a conformational change in CD4 and gp120 occurs, opening up an additional site for gp120 to enable binding to the co-receptor, i.e. chemokine receptor 5 (CCR5) or chemokine receptor 4 (CXCR4) on the cell surface.

Fusion of the viral and cellular membranes leads to translocation of the viral capsid into the cytoplasm. The capsid is taken up by an endosome, and a change in the pH value in the phagosome induces the release of the capsid contents into the cytoplasm. Activation of reverse transcriptase takes place in the cytoplasm.

HIV RT transcribes the single-strand HIV RNA genome into DNA (complementary DNA or cDNA). In parallel to DNA synthesis, the RNA strand is degraded enzymatically by RNase H, followed by conversion of single-stranded cDNA into double-stranded DNA (proviral DNA) by the DNA-dependent DNA polymerase activity of RT. This proviral DNA is transported via nucleopores into the cell nucleus in the form of a complex consisting of the integrase and linear or circular proviral DNA. The integrase then inserts at random the proviral genome into the human host cell genome. Integration of the proviral DNA finalizes the HIV infection of the cell and the establishment of a persistent infection.

Epidemiology

According to present knowledge, the spread of HIV started at the beginning of the 20th century. Zoonotic transmission of SIVcpz from chimpanzees (Pan troglodytes) occurred for HIV-1 group M and group O around 1920 and HIV-1 group N around 1960 in West Central Africa. HIV-2 was transmitted zoonotically from Sooty Mangabey (Cercocebus atys) to humans in West Africa around 1940. Molecular genetic analyses suggest that HIV-1 was exported to Haiti probably in 1966 and arrived in North America approximately 2 years later. Since the mid-1980s the different HIV-1 M subtypes have been spreading, leading to a global pandemic. In contrast to HIV-1, HIV-2 initially remained restricted to West Africa because of its significantly lower infectivity. After HIV-2 was exported to Portugal and France probably during the mid-1960s, the spreading of HIV-2 with a low prevalence especially in Europe, South America, and Asia is documented. Globally, an estimated 37.7 million people were living with HIV in 2020.

Transmission

HIV can enter the body via intact mucous membranes, eczematous or injured skin or mucosa, and parenteral inoculation.

The major factors leading to the transmission of HIV are as follows:

Having unprotected sexual intercourse with a person infected with HIV

Sharing injections, drug equipment with someone who has HIV.

Through vertical transmission i.e. from mother to child during pregnancy, birth, or breastfeeding.

Receiving blood transfusions, organ transplants, or tissue transplants that are contaminated with HIV.

Symptoms

Acute HIV Infection

A few weeks after getting HIV, many people have flu-like symptoms, which may last days or weeks. These symptoms can include fever, headache, tiredness, and enlarged lymph glands in the neck and groin area. Some people may have no symptoms.

Chronic HIV Infection

In the next stage of HIV infection, the virus still multiplies, but at very low levels. People may not feel sick or have any symptoms.

If they are not getting treatment for HIV during this stage, they can still pass the virus to other people. Getting and staying on treatment prevents passing HIV to others.

Without HIV treatment, people can stay in this stage for a decade or more, although some move through this stage faster.

AIDS

AIDS is the most advanced stage of HIV when a person's immune system is severely weakened and has difficulty fighting infections and certain cancers. At this stage, serious symptoms develop, such as:

• Rapid weight loss

• Serious infections

• Pneumonia

• Recurrent fevers

• Prolonged swelling of the lymph nodes

• Skin blotches

• Prolonged diarrhea

• Sores of the mouth, anus, or genitals

• Memory loss

• Depression

• Other neurologic disorders

NOTE: The only way to know for sure if you have HIV is to get tested. One CANNOT rely on symptoms to tell whether you have HIV.

Diagnosis

The detection systems can be differentiated into two principles of detection namely Antibody and Virus detection. HIV RNA can be detected in the blood using a nucleic acid test (NAT) about 11 days after infection.

Antibody screening tests

HIV antibody screening tests are used for the primary diagnosis followed by a confirmation test in the case of a reactive result in the screening assay. In addition to the ELISA (enzyme-linked immunosorbent assay) or variants of this test system, particle agglutination tests are used. Approved ELISA tests contain antigens of HIV-1 group M, particularly HIV-1 M: B, group O, and HIV-2. Depending on the manufacturer, additional antigens derived from the reverse transcriptase and the p24 protein are included in the test systems. An infection can be detected serologically after 3 weeks.

Confirmatory test (Western blot, Immunoblot)

The Immunoblot/Western blot assay was introduced as serologic confirmatory tests, but these test systems have a lower sensitivity in the early phase of HIV infection than antibody screening tests or p24 antigen detection systems. Only if the criteria for a positive Immunoblot/Western blot are fulfilled can the HIV infection be considered as confirmed.

p24 Antigen test

The p24 protein forms the inner capsid. Each virus particle contains approximately 2,000 p24 molecules. Detection of p24 antigen is performed using a combination of polyclonal or monoclonal antibodies, following the principle of the sandwich ELISA technique.

NAT - Nucleic Acid Amplification Technology

Diagnosis of an HIV infection can be performed by determining proviral DNA in cells or of the viral RNA genome in plasma. For analysis of the viral load and the presence of HIV in blood donations, RNA is extracted from virus particles in plasma. Genome detection can be done either via direct amplification of defined target sequences or through the use of probes with subsequent signal amplification.

Treatment

HIV infection has a very complex pathogenesis and varies substantially in different patients. Therefore, it can easily be considered a very host-specific infection. The specificity of pathogenesis often complicates treatment options that are currently available for HIV infection. Effective management of HIV infection is possible using different combinations of available drugs. This method of treatment is collectively known as antiretroviral therapy (ART). Standard ART consists of a concoction of at least three medicines (termed as “highly active antiretroviral therapy” or HAART). Effective ART often helps control the multiplication of HIV in infected patients and increases the count of CD4 cells, thus, prolonging the asymptomatic phase of infection, slowing the progression of the disease, and also helping in reducing the risk of transmission.

The following are the important HIV drug classes:

Reverse transcriptase inhibitors

Protease inhibitor

Fusion inhibitor

Chemokine Receptor 5 Antagonist

Integrase Strand Transfer Inhibitors

Prevention

Anyone can get HIV but steps can be taken to protect self from HIV

Protected sexual intercourse with the use of condoms, diaphragms, etc.

Limit number of sexual partners

Get tested and treated for STDs

Get Pre-exposure Prophylaxis

Use of sterile equipment while injecting drugs.

Social impact and stigma

"We live in a completely interdependent world, which means we cannot escape each other. How we respond to AIDS depends, in part, on whether we understand this interdependence. It is not someone else's problem. This is everybody's problem." - Bill Clinton

HIV stigma refers to the negative attitudes and beliefs about people with HIV. It is the prejudice that comes with labeling an individual as part of a group that is believed to be socially unacceptable.

The patients are being discriminated against based on outdated and prejudiced views of the people surrounding them. In many families and societies being diagnosed with HIV simply means being social outcasts. People fear they may contract the disease through mere casual contact or handling the articles being used by them. This leads to them being shunned by society.

As with any disease, recovery from HIV needs the mental stability of the person. Unfortunately regarding this disease mental stability is a luxury that is not given to the person. It is considered that it is the individual's fault that they have contracted this disease. HIV is frequently transmitted through actions that are kept secret, hidden, or are illegal- a characteristic that makes this disease unique. Misconceptions have shaped beliefs; unfortunately, most people in our society do not realize that it is not the patient’s intention to be infected by HIV. Consequently, despair, exhaustion, and helplessness approaching panic are experienced by most patients, who are faced with society’s rejection, losing their hopes for a prosperous future. It is almost impossible to conceptualize the degree of suffering the human body undergoes and the despair of the human mind in a societal group devastated by AIDS.

Like any other stigma it is rooted in the fear of HIV. Many of our ideas about this disease emerge from that which appeared first in the early 1980s. There still exist numerous misconceptions about how HIV is transmitted and what it means to live with HIV today. As with any other taboo, overcoming this social stigma requires the eradication of the fear associated with it. This fear can only be eradicated through education. Multiple efforts are being taken by WHO and local healthcare authorities to educate the public about this disease; mainly its transmission and modes of prevention. People need to realize that speaking with the patient or casual contact with the infected does NOT spread this disease. The people suffering from AIDS need to be accepted in society. They need support and strength from the ones surrounding them to combat it.

The theme of World AIDS day 2021 is " End inequalities. End AIDS" , this year we take the fight not to the hospitals but we fight it within us. We fight to accept the harsh reality that these patients live in. This year we try to make this world more hospitable to them.

Only with the acceptance of the true reality can mankind produce a united front to combat this disease.

References

Origin of HIV and the AIDS Pandemic by Paul M. Sharp and Beatrice H. Hahn

Human Immunodeficiency virus (HIV) by German Advisory Committee Blood (Arbeitskreis Blut) Subgroup 'Assessment of Pathogens Transmissible by Blood'

Current scenario of HIV/AIDS, Treatment Options, and Major Challenges with Compliance to Antiretroviral Therapy by Adnan Bashir Bhatti, Muhammad Usman and Venkataramana Kandi

The social stigma of HIV-AIDS : society’s role by Emmanuel N Kontomanolis, Spurgeon Michalopoulos and Zacharias Fasoulakis