HIV and AIDS: A Full Explanation

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HIV: Human Immunodeficiency Virus

HIV stands for Human Immunodeficiency Virus. It is a virus that attacks the human immune system, specifically targeting CD4 cells (T-helper cells), which play a central role in coordinating the immune response. By destroying these cells, HIV weakens the immune system, making it harder for the body to fight off infections and diseases.

HIV is transmitted through certain body fluids such as:

• Blood
• Semen
• Vaginal fluids
• Rectal fluids
• Breast milk

The virus can be transmitted through sexual contact, sharing needles, childbirth, and breastfeeding. It is important to note that HIV cannot be transmitted through air, water, saliva, sweat, tears, or casual contact.

AIDS: Acquired Immunodeficiency Syndrome

AIDS stands for Acquired Immunodeficiency Syndrome. It is the final stage of an HIV infection when the immune system is severely damaged and unable to fight off infections and diseases. A person with HIV is considered to have progressed to AIDS when their CD4 cell count drops below 200 cells per cubic millimeter of blood (normal range is 500-1,500) or when they develop one or more opportunistic infections, which are illnesses that take advantage of a weakened immune system.

Symptoms and Stages of HIV Infection

HIV infection typically progresses through three stages:

1. Acute HIV infection: This stage occurs within 2-4 weeks after infection and is characterized by flu-like symptoms such as fever, fatigue, swollen lymph nodes, sore throat, and rash. These symptoms usually last for a few weeks and then resolve. During this stage, the virus replicates rapidly, and the viral load (amount of virus in the blood) is very high, increasing the risk of transmission.
2. Chronic HIV infection: Also known as the asymptomatic or latent stage, this phase can last for many years (up to a decade or longer) without any symptoms. The virus continues to multiply at lower levels, and the person's viral load may decrease. During this stage, the person can still transmit the virus to others.
3. AIDS: As mentioned earlier, this is the final stage of HIV infection when the immune system is severely compromised. The person becomes susceptible to opportunistic infections and illnesses that a healthy immune system would typically be able to fight off.

Diagnosis and Treatment

HIV is diagnosed through blood tests that detect the presence of the virus or the body's immune response to the virus (antibodies). Early diagnosis and treatment are crucial to slow the progression of the disease and reduce the risk of transmission.

There is currently no cure for HIV, but antiretroviral therapy (ART) can help control the virus and prevent its progression to AIDS. ART involves taking a combination of HIV medications daily to suppress the virus, maintain a low viral load, and preserve the immune system. If taken consistently and correctly, ART can allow people with HIV to live healthy, long lives and reduce the risk of transmission to others.

Prevention

Preventing HIV transmission is key to controlling the spread of the virus. Some preventive measures include:

• Practicing safer sex by using condoms consistently and correctly
• Limiting the number of sexual partners
• Getting regularly tested for HIV and other sexually transmitted infections
• Using sterile needles and not sharing needles for drug use
• Taking pre-exposure prophylaxis (PrEP), a daily medication for people at high risk of HIV infection
• For HIV-positive pregnant women, receiving proper medical care and treatment to reduce the risk of transmission to their babies

By understanding the basics of HIV and AIDS, taking preventive measures, and getting early diagnosis and treatment, it is possible to control the spread of the virus and improve the quality of life for those living with HIV.

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Topic Highlights:-

• lipid-enveloped RNA virus which occurs as two types, HIV-1 and HIV-2, both of which cause AIDs.
• HIV is primarily a sexually transmitted disease but other modes of transmission include blood and blood products, tissue and organ donation, sharing of needles among intravenous drug users, needle stick injuries, and from an infected mother to the child.
• HIV infects the CD4+ cells, weakening the immune system, spread of infection gradually leads to immune compromise and AIDS.
• This animation explains the structure of HIV, the pathogenesis, immune response, clinical features, manifestation.

Transcript:-
Recognition of the AIDS pandemic dates back to 1981, when an increased incidence in the United States of two rather rare diseases, Kaposi’s sarcoma and Pneumocystis Carinii, now known as Pneumocystis jiroveci pneumonia was observed. Since these conditions were first seen in male homosexuals and intravenous heroin users in association with lowered immune competence and fatal infections, the term Acquired Immune Deficiency Syndrome (AIDS) was coined.

Three groups were involved in the discovery of the etiologic agent causing AIDS.

1. Luc Montagnier’s laboratory at the Pasteur Institute in Paris, who with Francoise Barre-Sinoussi, first identified the virus and named it the virus Lymphadenopathy Associated Virus (LAV).
2. Robert Gallo, working at the National Institute of Health in Washington, DC, named the virus the Human T-cell Lymphotropic Virus III (HTLV-III), and
3. Jay Levy’s laboratory at the University of California in San Francisco called it the AIDS-associated retrovirus (ARV).

The AIDS virus was subsequently named the Human Immunodeficiency Virus (HIV).

HIV is an RNA virus that belongs to the family Retroviridae; genus Lentivirinae. HIV occurs as two types, HIV-1 and HIV-2. Both HIV types cause AIDS, but with HIV-2 the disease progression is generally milder and slower. HIV-2 also has less mother-to-child transmission. HIV/AIDS is the fourth leading cause of death globally. Thus far, about 33.2 million people have been infected with HIV worldwide, with 2.5 million new infections and 2.1 million deaths reported during 2007.

HIV-1 variants are classified into three major phylogenetic groups: group M (main), group O (outlier) and group N (non-M/non-O).

Group M, which is responsible for the majority of infections worldwide, can be further subdivided into 10 recognized phylogenetic subtypes or clades – A–D, F–H, J, K and other circulating recombinant forms (CRFs). The original clade E is a recombinant virus containing part of clade A and a portion of a new subtype, labelled E. Clade G may also be a recombinant virus. HIV-2 has 8 groups (A–H) but no clades. It is genetically similar to the Simian Immunodeficiency Virus (SIV). Co-infection with HIV-1 and HIV-2 can occur.

HIV is primarily a sexually transmitted disease (STD), transmitted by heterosexual and homosexual practices: anal, vaginal, and oral sex. The other modes of transmission are through blood and blood products; tissue and organ donation; sharing of needles among intravenous drug users (IDUs); needle stick injuries among health care workers; and perinatal transmission from an infected mother to the child, transplacentally, during birth and via breast milk.

HIV is a lipid-enveloped virus measuring 90–120 nm in diameter. The viral genome consists of two, usually identical, copies of single-stranded RNA enclosed within a nucleoprotein core. When one cell is co-infected by two different viruses, recombination can take place in which the new virus has genetic portions of the two different viruses. Each of the genomic RNAs is attached to reverse transcriptase, an enzyme characteristic of the family Retroviridae. Reverse transcriptase transcribes the viral RNA into a single strand of viral DNA (cDNA), which is formed into double-stranded DNA using the viral enzyme. This double stranded DNA enters the nucleus and integrates into the host chromosomal DNA. This transcribed integrated viral particle is referred to as a provirus. The inner viral core is surrounded by a nucleocapsid protein shell or p24. The viral envelope is a host-derived lipoprotein membrane with viral glycoproteins that are identified as gp120 and gp41. Envelope proteins appear as spikes on the virion surface for binding to the cell and also function as transmembrane anchors during virus attachment.

HIV genes are characterized as structural and non-structural or accessory. The three structural genes are gag, pol and env. A gag gene determines the viral core and the inner shell. The precursor p55 protein is cleaved into the viral proteins p2, p24, p18 and p15. An env gene determines envelope synthesis. The precursor glycoprotein gp160 is cleaved into gp120 and gp41. gp120 encodes the spikes and gp41 determines the transmembrane anchoring glycoprotein. A pol gene codes for the enzyme reverse transcriptase (RT). The precursor p100 is cleaved into subunits p32 (integrase), p51 and p66 (Reverse transcriptase RT) as well as the p10 protease. The latter enzyme plays a role in cleaving the gag and pol proteins.

The accessory genes present in HIV are tat, rev, nef, vif, vpr, vpu, vpx, and the long terminal repeats (LTRs).

1. The tat protein is important for the transcription of the viral genome into the messenger RNA for the viral proteins
2. The protein produced from the rev gene regulates the viral mRNA expression and permits an unspliced message to be transferred into the cytoplasm of the cell to produce the viral proteins, including gp160.
3. The protein produced from nef has a variety of functions that can increase or decrease HIV replication.
4. The vif protein increases the viral infectivity and cell to cell transmission. It also helps in proviral DNA synthesis and virion assembly.
5. The vpr protein gene helps in HIV replication and transactivation that enhances viral replication.
6. The vpu protein (only present in HIV-1) helps in virus release.
7. The vpx gene (only present in HIV-2) participates in viral entry and infectivity.

In addition, at the 5' end or left-end portion of the viral genome there is a long terminal repeat (LTR) region which contains both promoter (enhancing) and suppressing elements that influence viral transcription.

The pathogenicity of the virus is primarily due to destruction of CD4 helper T cells that are vital for the induction and maintenance of immune responses to many pathogens. They are also responsible for immune competence. Their depletion impacts several aspects of cellular immunity. Infected cells also demonstrate a marked decrease in cytokine production, such as interleukin-2, gamma interferons and other lymphokines. This result affects both T-cell mediated immune response and B cell humoral activity. There is decreased antibody response to new antigens, polyclonal activation of B cells with hypergammaglobulinemia. Lack of certain cytokines can lead to defective function of macrophage and monocytes and microglial cells in the central nervous system, as well as reduce the function of dendritic cells, cytotoxic T lymphocytes and natural killer cells. Together, these immune abnormalities result in defective chemotaxis, intracellular antigen degradation and disruption in antigen presentation.

The reduction in CD4 T cells (infected and uninfected) and disease progression correlates with immune activation that results from HIV infection. This increased T cell activation can induce CD4 cell and CD8 cell apoptosis by certain processes such as the interaction of the Fas ligand and Fas antigen on cell surfaces. Production of pro-inflammatory cytokines like TNF-alpha, IL-6, IL-1 beta, IFN-alpha and gamma is also altered and can be involved.

HIV infection can cause a shift in immunoregulatory cytokines and chemokine production. Type-1 cytokine production, which helps in the generation of effector and memory T lymphocytes, is reduced. For example, IL-12, a natural killer cell stimulator is impaired in association with hyperproduction of IL-10, a type 2 cytokine. The type 2 cytokines can induce antibody responses.

During the asymptomatic infection period, viral replication in the blood is low. However production of progeny virions in lymphoid tissues continues until scarring depletes lymphoid tissue T cell reservoirs. Virus levels in the lymphoid tissue are kept under control in part by the immune system. CD8 T-cells of the lymphoid system, in particular, can reduce viral replication.

HIV infection is divided into different stages:

1. Stage 1 - Acute HIV infection: 1–2 weeks after infection, 50–75% of infected people present with non-specific symptoms such as low grade fever, headache, malaise, rash, and lymphadenopathy. This is called seroconversion illness or the acute retrovirus syndrome. Very early in infection, antibody titers are undetectable, i.e., antibody tests are negative, whereas viral p24 in the blood and viral RNA are demonstrable.
2. Stage 2 - Asymptomatic infection: Irrespective of seroconversion illness, there is a period of symptomless infection. Antibody tests are positive. The infection remains controlled until the immune system becomes so compromised that Stage 3 begins.
3. Stage 3 - Symptomatic infection: Years of viral activity cause damage to the immune system including destruction of the lymphatic tissue in the gastrointestinal tract and lymph nodes, as well as other tissues harboring the virus. Moreover, viral virulence is incurred with extensive loss of the CD4 helper T cells which cannot be replenished by the host immune system. These effects lead to progressive and irreversible immune deficiency. The patient can have lymphadenopathy and becomes prone to ‘opportunistic infections’ or develops HIV-related symptoms characterized by fatigue, fever, malaise, weight loss and diarrhea.
4. Stage 4 or AIDS: Due to severe damage to the immune system, major opportunistic infections and cancers develop. The World Health Organization (WHO) defines this stage by the presence of HIV wasting, opportunistic infections such as pneumocystis pneumonia, cytomegalovirus retinitis, esophageal candidiasis, extrapulmonary tuberculosis and cryptococcal meningitis. Cancers include Kaposi’s sarcoma and B cell lymphoma.

The clinical severity of AIDS is reflected by the type of infection and malignancy. Various systemic manifestations are:

1. Respiratory: Most common infection is pneumonia caused by Pneumocystis jiroveci (formerly called carinii). Even though seen in industrialized countries, Mycobacterium tuberculosis, Mycobacterium avium-intracellulare complex and atypical mycobacteria are more prominent in developing or resource limited countries. Pneumonias due to cytomegalovirus (CMV), cryptococcus and fungi are also seen. Malignancies, especially Kaposi’s sarcoma, may also be present with pulmonary manifestations.
2. Hematological: Idiopathic thrombocytopenic purpura (ITP), anemia, progressive lymphopenia in association with a drop in CD4 cell counts and cytopenias can be observed.
3. Gastrointestinal: Oral thrush, herpetic stomatitis, gingivitis, Kaposi’s sarcoma and hairy leukoplakia caused by Epstein-Barr virus involve the oral cavity. Diarrhea, distension and abdominal pain are common. Pathogens causing diarrhea include cryptosporidium, salmonella, mycobacteria, isospora and CMV. Systemic strongylosis can also occur.
4. Malignancies: Kaposi’s sarcoma, a non-metastasizing tumor that is often mucosal and cutaneous; Hodgkin’s and non-Hodgkin’s lymphomas (particularly B-cell lymphoma), primary central nervous system lymphoma, invasive cervical carcinoma, invasive anal carcinoma.
5. Central Nervous System: Typical CNS pathogens include cryptococcus, M. tuberculosis and Toxoplasma gondii. Other CNS infections include CMV, herpes simplex virus, JC papovavirus, and candida species. CNS lymphomas (Epstein-Barr virus positive) are common.
6. Dementia: HIV crosses the blood-brain barrier and can cause toxic and cytopathic damage to the CNS directly or via inflammatory cytokine production. This effect manifests itself as encephalopathy that progresses into loss of brain functions and dementia.
7. Cutaneous: Herpetic lesions, candidiasis, xeroderma, molluscum contagiosum and folliculitis are common lesions.
8. Ophthalmic: Cytomegalovirus retinitis is the most common ophthalmic disease reported by AIDS patients, which can lead to blindness. As AIDS progresses, Progressive Outer Retinal Necrosis is seen.