AIDS

AIDS is the late stage of H.I.V. infection that occurs when the body's immune system is badly damaged because of the virus. Human immunodeficiency virus (H.I.V.) is a virus that attacks the body's immune system. 

1.0Structure and Types of HIV Virus 

• A person with HIV is considered to have progressed to AIDS when either of the following occurs:
• Their CD4 cell count falls below 200 cells per cubic millimeter of blood (normal CD4 counts in a healthy immune system range from 500 to 1,600 cells/mm³), or
• They develop one or more opportunistic infections, regardless of their CD4 count.
• HIV has a complex structure made up of several essential components:
• RNA Genome : The virus contains two copies of single-stranded RNA.
• Capsid : A cone-shaped core that holds the viral RNA.
• Envelope : The outermost layer of HIV, which includes a surface glycoprotein (gp120) and a transmembrane glycoprotein (gp41).
• Matrix : A protein layer on the inner surface of the envelope, providing structural support.
• Viral Proteins : The capsid houses key enzymes—protease, integrase, and reverse transcriptase critical for HIV replication.
• Lipid Bilayer : The virus is encased in a lipid bilayer membrane.
• Host Proteins : HIV also incorporates proteins from the host cell it last infected into its structure. 

• HIV-1 is the most common type of HIV and accounts for 95% of all infections, whereas HIV-2 is relatively uncommon and less infectious. 
• HIV-2 is mainly concentrated in West Africa and the surrounding countries. HIV-2 is less fatal and progresses more slowly than HIV-1.

2.0Pathogenesis

• It refers to how the virus causes disease, involving the infection and destruction of immune cells, leading to immune system failure over time.
• The human immunodeficiency virus (HIV) undergoes a complex life cycle involving seven key stages:
• Binding : HIV attaches to a CD4 cell by using its glycoproteins to bind to receptors on the cell surface.
• Fusion : HIV’s outer membrane merges with the CD4 cell membrane, allowing its capsid to enter the cell.
• Reverse Transcription : HIV’s RNA is converted into DNA with the help of the enzyme reverse transcriptase.
• Integration : The newly formed HIV DNA integrates into the host cell’s DNA using the enzyme integrase.
• Replication : The host cell’s machinery transcribes the HIV DNA into new HIV RNA and proteins.
• Assembly : New HIV RNA and proteins assemble into immature HIV particles near the cell membrane.
• Budding and Maturation : The immature HIV particles bud off from the cell membrane. The protease enzyme then rearranges the viral proteins, maturing the HIV particle, making it infectious.

3.0Modes of Transmission

• H.I.V. is spread mostly through four body fluids
• People can get H.I.V. through:
• Vaginal/ anal sex without a condom.
• Sharing drug injecting equipment.
• Mother-to-child transmission during pregnancy.
• Coming into contact with contaminated blood.
• Getting tattoos or body piercings with unsterilized needle

HIV is NOT spread through:

4.0Clinical features of HIV infection

• AIDS is only the last stage in the wide spectrum of clinical features in H.I.V. infection. 
• The Centers for Disease Control (U.S.A.) has classified the clinical course of H.I.V. infection into various groups (Table).
• The natural evolution of H.I.V. infection can be considered in the following stages.

5.0Summary of Classification System for HIV Infection

(Centre for Disease Control, U.S.A.)

• Acute H.I.V. infection: Within a few weeks of infection with H.I.V., about 10-15 percent of persons experience low-grade fever, malaise, headache, lymphadenopathy/sometimes with rash and arthropathy resembling glandular fever. Rarely, there may be acute encephalopathy. Spontaneous resolution occurs within weeks. Tests for H.I.V. antibodies are usually negative at the onset of the illness but become positive during its course. Hence, this syndrome has been called seroconversion illness', though, in the majority of those infected with H.I.V., seroconversion occurs without any apparent illness; H.I.V. antigenaemia (p24 antigen) can be demonstrated at the beginning of this phase.
• Asymptomatic infection: All persons infected with H.I.V. pass through a symptomless infection lasting for several months or years. They show positive H.I.V.  antibody tests during this phase and are infectious. This phase leads to  full-blown AIDS, either directly or through cytopenias, minor opportunistic  infections, persistent generalized lymphadenopathy, or AIDS-related complex  (A.R.C.), as described below.
• Persistent Generalised Lymphadenopathy (PGL): This has been defined as the presence of enlarged lymph nodes at least-1.0 cm, in diameter, in two or more noncontiguous extrainguinal sites, that persist for at least three months, in the absence of any current illness or medication that may cause lymphadenopathy.
• AIDS-Related Complex (ARC): This group includes patients with considerable immunodeficiency, suffering from various constitutional symptoms or having minor opportunistic infections. The typical constitutional symptoms are fatigue, unexplained fever, persistent diarrhea and marked weight loss of more than 10 percent of body weight. The common opportunistic infections are oral candidiasis herpes zoster, hairy cell leukoplakia, salmonellosis or Tuberculosis Generalised lymphadenopathy and splenomegaly are usually present. ARC patients are usually severely ill and many of them progress to AIDS in a few months.
• AIDS: This is the end stage disease representing the irreversible breakdown of Immune defense mechanisms, Leaving the patient prey to progressive opportunistic infections and malignancies.
• Dementia: HIV may cause direct cytopathogenic damage in the central nervous system. It can cross the blood brain barrier and cause encephalopathy leading to loss of    higher functions, progressing to dementia.
• Pediatric AIDS: About half the number of babies born to infected mothers are infected with HIV Many of them may not survive for a year. Children may also acquire the infection from blood transfusion or blood products.

There are many differences between adult and pediatric AIDS. Children develop humoral immunodeficiency early, leading to recurrent infections. Failure to thrive, diarrhea, lymphadenopathy, tuberculosis, opportunistic bacterial infections are common infestations in pediatric AIDS.

6.0 Immunological abnormalities in HIV infection

7.0Diagnosis

1. Enzyme-Linked Immunosorbent Assay (ELISA)

The most common HIV tests use blood samples to detect infection. The enzyme-linked immunosorbent assay (ELISA) identifies HIV antibodies in a patient's blood. If the ELISA test result is positive (reactive), a follow-up confirmatory test, like the Western blot, is necessary to establish a definitive diagnosis. While false negatives or positives are very rare, they can occur if the patient has not yet developed antibodies to HIV or due to laboratory errors.

2. Western Blot Test

• The Western blot test is commonly employed to confirm an HIV-positive diagnosis. It works by separating blood proteins and identifying specific proteins that indicate an HIV infection. This test is often used to confirm a positive result from an ELISA test.
• Another method, the Polymerase Chain Reaction (PCR) test, is designed to detect HIV's genetic material, known as RNA. PCR tests can screen donated blood and identify infections very early, often before antibodies form. Despite their high accuracy, PCR tests are less frequently used than other HIV tests due to their cost, complexity, and time-intensive nature.

8.0Treatment

1. Classification of Antiretroviral Therapy

(A) Nucleoside and Nucleotide Reverse Transcriptase inhibitors (NRTIs)

Eg : Zidovudine, Stavudine, Lamivudine, Abacavir, Tenofovir.

(B) Non-nucleoside Reverse transcriptase inhibitors (NNRTIs)

Eg : Nevirapine, Delavirdine, Etravirine.

(C) Protease inhibitors 

Eg : Saquinavir, Indinavir, Ritonavir, Amprenavir, Darunavir.

(D) Entry inhibitors 

Eg : Enfuvirtide, Maraviroc

(E) Integrase inhibitors 

Eg : Raltegravir

2. Combination Therapy for HIV

• Highly active antiretroviral therapy (HAART) is the recommended approach when HIV is diagnosed.
• The therapy should consist of a 3 drug combination usually to prevent resistance.
• The combination should contain at least 2NRTIs + 1 NNRTI or 1 Protease Inhibitor or 1 Integrase Inhibitor.