HIV (Human Immunodeficiency Virus): History, Introduction, Morphology,

HIV (Human Immunodeficiency Virus): History, Introduction, Morphology, Pathogenesis, Lab Diagnosis, Epidemiology, Prevention and Prophylaxis

History of HIV (Human Immunodeficiency Virus)

Acquired immunodeficiency syndrome (AIDS) was first reported in 1981 USA. Montagnier (Pasteur Institute of Paris ) in 1983 isolated HIV from an African patient who suffered from persistent generalized lymphadenopathy and named lymphadenopathy-associated virus (LAV). Human Immunodeficiency Virus (1984): Robert C. Gallo, BBL, NIH, USA isolated Retrovirus and named HTLV-III (Human T Lymphotropic Virus) International Committee on Virus Nomenclature gave generic name ”HIV” in 1986.

AIDS: It is a fatal disease state arising as a result of infection with HIV. It is the result of a complex interaction between the process of viral infection and the host’s response and is characterized by the depletion of cells of the immune system specifically the T4 Lymphocytes. This breakdown of the immune system allows for the opportunities for infection such as; Viral’ Fungal’ bacterial, parasitic infection to invade, and become lethal and neoplasm to occur. AIDS develops after a medium time of 10 years following infection. HIV occurs in 2 forms – HIV 1 and HIV 2. They have about 40% genetic homology with each other.

Classification of HIV

Family: Retroviridae

Subfamily: Lentvirinae

Genus: Lentivirus

Species: HIV-1 and HIV-2

Morphology of Human Immunodeficiency Virus

100- 140 nm in diameter with the cylindrical core.

Envelope: Host derived lipid and protein

Capsid (Shell): The protein coat surrounds the core of the virus (P17, P18) and is icosahedral symmetry.

The nucleocapsid surrounds the inner cone-shaped core.

Core Contains :

2 identical single strands of RNA and carries genetic materials of virus
Structural protein :p25 (p25,p26)
Reverse transcriptase and other enzymes such as Ribonuclease, Endonuclease

HIV genome:

The Structural Gene of Human Immunodeficiency Virus

env gene encodes gp 120/gp41
gag gene encodes capsid and core p25, p25
pol gene encodes for reverse transcriptase gene and p31, p61, p52

The regulatory gene of the Human Immunodeficiency Virus

Controls:

Assembly of viral protein
Infectivity of virus
Viral replication and latency

The function of the regulatory gene of HIV

Tat =Trans activator gene found in the nucleus of infected cells and essential for Viral replication.

Rev gene = Regulatory gene which regulates the production of viral protein

Vif gene = Virion infectivity factor gene is necessary to produce infected particles.

Nef gene = negative regulating factor gene is responsible for the slowdown of transcription of the viral genome which may contribute to keeping the virus in dormant form

Vpr gene – stimulates promoter region of the virus Vpu gene – in HIV 1, it enhances maturation and release of progeny virus from cells.

Vpx – in HIV 2, it enhances maturation and release of progeny virus from cells.

Mode of Transmission of Human Immunodeficiency Virus

It completes by following methods-

Sexual contact
Parenteral transmission
Perinatal transmission

Types of exposure Relative risk% per exposure

Sexual intercourse ( anal, vaginal, oral): 0.1-1.0

Transfusion of blood and blood products: >90

Tissue and organ donation: 50-90

Injection and injury: 0.5-1.0

Mother to baby: 30

Pathogenesis of AIDS

HIV comes into contact with a suitable host cell, mainly CD4 lymphocytes, after entering the bloodstream. Once in the cell, RNA is transcribed by reverse transcriptase into DNA (provirus). The provirus is integrated into the genome of the infected cell causing a latent infection. The long and variable incubation period of HIV infection is because of the latency. From time to time, lytic infection is initiated and releases progeny virions to infect other cells. In an infected person, HIV can be isolated from blood, lymphocytes, cell-free plasma, cervical secretion, semen, saliva, urine, tears, and breast milk.

AIDS-defining condition

Following infection and other conditions have been included as AIDS-defining conditions:

Infection

Pneumocystis carinii pneumonia
Disseminated atypical mycobacterial disease
Cerebral Toxoplasmosis
Oesophageal Candidiasis (diarrhea more than 1 month )
Extrapulmonary Cryptococcosis
Cytomegalo virus (CMV) retinitis
Herpes Simplex Virus infections
Mucocutaneous ulcer lasting more than 1 month
Dissiminated Coccidiodomycosis
Tuberculosis involving at least one extrapulmonary site
Recurrent nontyphoid septicemia
Extraintestinal Strongyloidosis
Progressive multifocal leukoencephalopathy

Neoplasm

Kaposi’s sarcoma
Primary lymphoma of the brain
Another non-Hodgkins lymphoma of B-Cell or unknown immunological phenotype

Resistance

Thermolabile, inactivated in 10 minutes at 60°C, and in seconds at 100°C.

Withstands lyophilization.
At room temperature, in dried blood, it may survive for up to 7 days.

Laboratory Diagnosis of Human Immunodeficiency Virus

It completes two methods i.e. specific tests and non-specific tests.

Specific Tests

Detection of antigen e.g.,p24
Surrogate markers e.g., the CD4 cells count ( less than 200/ µl of blood)
Virus isolation by co-cultivation of the patient’s lymphocytes with uninfected lymphocytes in the presence of IL-2.
Detection of antibody to human immunodeficiency virus
Viral load

ELISA

Particle agglutination test

Rapid Immuno dot test to detect HIV antibody

Indirect Immunofluorescence test

Western blot (WB):

Interpretation of Western Blot

Positive :

When the Western blot (WB) contains 2 or 3 major bands, it has diagnosis significance.

For example:

Anti gp 160/ 120

Anti gp 41

Anti p 24

Negative :

WB is without any HIV -1 specific bands

Intermediate

When the WB contains one or more viral-specific bands but insufficient bands to call the result positive.

The intermediate band should be repeated. If still intermediate should be retested after 2-3 months.

Nucleic acid technology

RT-PCR to detect proviral DNA in the lymphocyte

Non-specific tests

Total and differential leukocyte count (TLC and DLC): Leukopenia and lymphocyte count less than 400 per microliter.
T-lymphocyte subset assays: The normal CD4 and CD8 ratio are 2:1, which is reversed to 0.5:1 in cases of AIDS. The CD4 lymphocyte count goes below 200 per microliter.
Platelet count: Thrombocytopenia
IgG and IgA levels: Increased
Skin test for cell-mediated immunity

Treatment of AIDS

Antiretroviral drugs e.g. didanosine, zidovudine, indinavir, lopinavir, nelfinavir,
ritonavir, etc.
Drugs to prevent opportunistic infections
Drugs to relieve symptoms

Epidemiology of HIV

The human immunodeficiency virus is transmitted through blood, semen, vaginal fluid, and from an infected mother to her baby. It is predominantly a sexually transmitted disease (STD). It can occur in homosexuals as well as heterosexuals. The danger of needle-stick injury remains in medical and paramedical personnel, though the risk of infection has been estimated to be about 1%. Medical and paramedical staff are to be educated on caring for patients with HIV infection. Two serotypes of the human immunodeficiency virus are recognized, HIV-1 and HIV-2, HIV-1 is worldwide in distribution, while HIV-2 is principally found in West Africa. AIDS cases resulting from HIV-1 or HIV-2 infection are clinically indistinguishable. About 60% of adults infected with HIV will develop AIDS within 5 to 10 years and the vast majority of infected individuals will develop AIDS eventually. Virtually all persons diagnosed as having AIDS die of the disease. In Africa, the major manifestation of AIDS is pronounced wasting so that it has been named the slim disease.

Prevention

The recommended preventive measures are as follows-

Sexually contact: Transmission of the virus can be avoided by the use of condoms.
Sharing needles: It is not acceptable to exchange infected syringes or needles.
Blood: It is important to screen both blood and blood products for HIV. This also refers to the cornea, blood, marrow, kidney, and other organs being donated.
Isolation of AIDS patients and initiation of treatment.
Control of infection: Screening of people within risk categories helps to classify individuals infected with HIV.

Prophylaxis

No effective vaccine has been discovered yet. The high rate of mutation of the virus has made the vaccine difficult to produce. For vaccine preparation, many methods have been explored. That includes vaccines with (i) I modified whole virus (ii) envelope-based subunit glycoprotein (iii) targets anti-CD4 antibody cell proteins. A number of these candidate vaccines are currently undergoing human clinical trials.

Keynotes on Human Immunodeficiency Virus

HIV-1 is worldwide in distribution, while HIV-2 is mainly found in West Africa.
Post-exposure prophylaxis for HIV (PEP): PEP is the use of ARVs within 72 hours of exposure to HIV to prevent infection. PEP includes counseling, first aid care, human immunodeficiency virus testing, and administration of a 28-day course of antiretroviral therapy drugs with follow-up care. WHO recommends PEP use for both occupational and non-occupational exposures, and for adults and children.
Viral load: It is the amount of human immunodeficiency virus in the blood (particularly the number of copies of human immunodeficiency virus RNA) and it also helps determine how rapidly the CD4 count is likely to decrease in the next few years.
Post Exposure Prophylaxis (PEP): The risk of acquiring human immunodeficiency virus infection may result from exposure to blood, body fluids, other potentially infected materials, or instruments contaminated with one of these materials. The risk of infection varies according to exposure types and other variables. The majority of exposures and other variables. Infection does not result from most exposures. During the management of infected patients, health workers are normally at very low risk of acquiring an infection. The exposure code (EC) and HIV status code (HIV SC) of the sources of exposure are followed. In combination, Zidovudine 300 mg BD and Lamivudine 150 mg BD are used for a four-week duration. Indinavir 800 mg TDS is applied to this mixture of medicines according to PEP guidelines in selected cases. These medications must be started within an hour or two in order to be effective. When deciding to start PEP, both the risk of infection and the potential side effects of antiretroviral drugs should be carefully considered. The injured area of the wound should be thoroughly cleaned with soap and water in addition to PEP. Also, antiseptics can be used.

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