JAYS QUIZPAD: AIDS Overview and Global Statistics

Acquired Immunodeficiency Syndrome (AIDS)

• AIDS is a disease caused by the retrovirus HIV, leading to profound immunosuppression.
• This can result in opportunistic infections, secondary cancers, and neurological problems.

Secondary Immunodeficiencies

• HIV transmission mainly happens through unprotected sex, contaminated blood products, needles, and during pregnancy/breastfeeding.
• Saliva and tears do not transmit HIV.

Epidemiology and Statistics

• Since its discovery in 1981, AIDS has become an epidemic.
• Globally, an estimated 42 million people are living with HIV/AIDS.
• 38.6 million are adults, 19.2 million are women, and 3.2 million are children under 15.
• Genetic research suggests HIV originated in West-Central Africa in the late 19th or early 20th century.
• HIV/AIDS has had a significant impact on society, causing illness and discrimination.

Global Estimates of HIV/AIDS (2001)

• Global map showing estimated numbers of adults and children with HIV/AIDS, as of end 2001.
• Various regions have variable numbers reported (in millions).
• Total estimated adults and children living with HIV/AIDS: 40 million.

HIV and Life Cycle

• Two main types of HIV: HIV-1 and HIV-2.
• HIV is a retrovirus with two copies of single-stranded RNA genome.
• The genome contains gag (core protein), pol (enzymes), and env (envelope protein).
• The virus encodes 6 regulatory and accessory proteins.

HIV and Host Cell Infection Mechanisms

• HIV uses reverse transcriptase to convert viral RNA to DNA, which then integrates into the host's DNA.
• HIV has marker proteins (gp120) on its surface to recognize and infect specific immune cells.
• The protein coat contains MHC-I and MHC-II molecules.

Complete Activation of HIV

• CD4 is recognized by the virus but a costimulatory signal is necessary for viral attack.
• T cells: coreceptor is CXCR4, which also acts as a receptor for the chemokine SDF-1.
• There is competitive inhibition between chemokine and HIV, leading to the T-tropic HIV strain.

Infection of Human Cell with HIV

• HIV gp120 surface protein binds CD4 on target cells.
• Transmembrane component gp41 binds coreceptor CXCR4 for fusion.
• Viral genome and proteins enter the host cell within a nucleocapsid.
• Reverse transcriptase transcribes the viral ssRNA genome into a double-stranded DNA molecule (provirus).
• The provirus is integrated into the host's DNA.

HIV Replication and Host Impact

• Virus infects helper T cells (T_H) in local mucosal surfaces.
• Rapid spread to lymphoid tissue, glial cells, and genital secretions.
• Cytotoxic T cells appear within weeks of initial infection.
• Neutralizing antibodies may appear.
• Replication process begins after a short period.

HIV Replication and the Immune System

• Hosts develop an immune response, but high viral replication error rates mean high mutation rates.
• Repeated replication and mutation allow HIV to persist in lymph nodes.
• Infected cells can be killed directly or indirectly by immune mechanisms.
• After months, a balance is established between virus replication, immune response, and available cells, with the disease entering a chronic phase.
• High rate of viral replication leads to a decline in circulating CD4+ T cells.

HIV Impact on Lymphoid Organs and Immune Cells

• 99% virus replication in CD4+ T cells of lymphoid organs, 1% in monocytes and resting CD4+ T cells.
• HIV infection with CD4+ T cells declining below 200 cells/µL leads to opportunistic infections.
• Risk of opportunistic infections and malignancies increases when CD4+T cell count is below 50 cells/µL.
• Rate of immunologic and clinical progression varies between individuals, closely tied to virus replication.

AIDS Signs and Symptoms

• Early symptoms resemble a flu, lasting 2-4 weeks. -Common symptoms: fever, headache, sore throat, swollen lymph nodes, rash, diarrhea, weight loss. -Opportunistic infections like Pneumocystis carinii pneumonia (PCP) appear as the immune system weakens.
• CD4 lymphocyte count below 200 cells per microliter (µL) suggests immune deficiency.
• Soaking night sweats, dry cough, shortness of breath, and persistent/high fever are later-stage symptoms.
• Persistent white spots/lesions, headaches, blurred vision, and prolonged lymph node swelling also occur.
• Associated cancers, like Kaposi's sarcoma, may develop.
• Children experience different symptoms like difficulty gaining weight, delayed development, and increased susceptibility to childhood illnesses.

HIV Testing

• ELISA is the initial screening test for HIV antibodies.
• Western blot confirms a positive ELISA result to rule out false positives.
• Indirect fluorescent antibody (IFA) and polymerase chain reaction (PCR) tests may confirm results or detect HIV earlier.

HIV Treatment

• Highly Active Antiretroviral Therapy (HAART) is the main treatment, using a combination of antiretroviral drugs like nucleoside reverse transcriptase inhibitors (NRTIs).
• HAART considers 200 to 350 CD4+ cells/mm3 as a target range.
• Other classes include non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors.

Future of HIV Treatment

• Scientists are researching more potent protease inhibitors, less toxic reverse transcriptase inhibitors, and new drug classes, such as fusion and integrase inhibitors.