HIV: Types, Targets, and Mechanisms

No new information was provided; therefore, the study notes are identical to the original ones.

HIV Overview

• HIV (human immunodeficiency virus) targets cells of the immune system, leading to immunodeficiency.
• Immunodeficiency increases the risk of infections and tumors, which are referred to as AIDS (acquired immunodeficiency syndrome).
• Two main types of HIV exist: HIV-1 and HIV-2.
• HIV-1 is more common worldwide and in the US, predominantly associated with AIDS.
• HIV-2 is rarer and mostly found in western Africa and southern Asia.
• "HIV" typically refers to HIV-1 due to the rarity of HIV-2.

Cellular Targets and Mechanisms

• HIV targets CD4+ cells, which include macrophages, T-helper cells, and dendritic cells.
• The CD4 molecule is crucial for immune cell attachment and communication.
• HIV uses its gp120 protein to attach to the CD4 molecule on target cells.
• HIV also requires a co-receptor (CXCR4 or CCR5) to enter the cell.
• CXCR4 co-receptors are mainly found on T-cells.
• CCR5 co-receptors are found on T-cells, macrophages, monocytes, and dendritic cells.
• Individuals with homozygous mutations in CCR5 may have resistance or immunity to HIV.
• Heterozygous mutations in CCR5 can slow disease progression.
• HIV is a single-stranded, positive-sense, enveloped RNA retrovirus.
• It uses reverse transcriptase to create proviral DNA from its RNA.
• The proviral DNA integrates into the host cell's DNA in the nucleus.
• Immune cell activation inadvertently transcribes and translates new HIV viruses.

Viral Tropism and Infection Phases

• HIV is prone to making errors during replication, leading to different strains with varying behaviors.
• Viral tropism refers to the host cell preference of these HIV strains.
• The R5 strain of HIV, which binds to the CCR5 co-receptor, infects macrophages, dendritic cells, and T cells early in the acute infection.
• Dendritic cells capture the virus and migrate to lymph nodes, leading to high viral replication.
• Acute infection symptoms resemble flu or mononucleosis.
• The immune system responds, controlling viral replication, and the patient enters the chronic or clinically-latent phase, with lower, detectable viral levels by 12 weeks.
• The chronic phase can last 2-10 years, with a slow increase in viruses and a decrease in T cells.
• During the chronic phase, T cell counts are usually above 500 cells / mm3.

Disease Progression and AIDS

• Some patients develop an X4 strain of HIV during the chronic phase which targets the CXCR4 coreceptor, primarily found on T-cells.
• X4 strains can destroy CD4 T cells in lymphoid tissues.
• Lymphadenopathy and minor infections like oral hairy leukoplakia and oral candidiasis occur when T cell counts drop to 200-500 cells / mm3.
• AIDS is diagnosed when T cell levels fall below 200 cells / mm3, indicating a severely compromised immune system.
• AIDS symptoms include persistent fever, fatigue, weight loss, and diarrhea.
• AIDS-defining conditions include recurrent bacterial pneumonia, pneumocystis pneumonia, candidiasis of the esophagus, Kaposi sarcoma, and primary lymphoma of the brain.
• Death in AIDS patients often results from infections that a healthy immune system could manage.

Transmission and Diagnosis

• Male-to-male transmission is the most common mode in the US.
• Male-to-female transmission is more common in resource-limited settings.
• HIV is present in vaginal and cervical fluids, allowing for female-to-male transmission.
• Sexual intercourse accounts for over 75% of HIV cases.
• Other transmission routes include intravenous drug abuse and mother-to-child transmission (via placenta, delivery, or breast milk).
• Less common modes include accidental needlesticks and blood transfusions.
• HIV tests include antibody tests, antibody/antigen tests, and RNA/DNA tests.
• Antibody tests detect antibodies against HIV.
• Antigen tests and RNA/DNA tests directly detect the virus.
• Antibody/antigen tests are recommended for screening due to their ability to identify early infections.
• A confirmatory test (antibody or nucleic acid test) is recommended following a positive screening test.

Treatment

• There is currently no cure for AIDS.
• Antiretroviral therapy (ART) can prolong life, improve health, and reduce transmission risk.
• ART involves a combination of medicines, known as an HIV regimen.
• ART slows HIV replication, allowing the immune system to recover and fight off infections.