HIV Infection and Transmission Overview

HIV Infection

• HIV infection is a viral disease characterized by its etiology, pathogenesis, natural history, diagnosis, and treatment.
• Acquired Immunodeficiency Syndrome (AIDS) was first recognized in the United States in the summer of 1981.
• The oldest known case dates back to 1959 in Kanshasa, Democratic Republic of Congo, West Africa.
• Scientists Harald zur Hausen, Françoise Barré-Sinoussi, and Luc Montagnier isolated the virus from lymph node cells of AIDS patients in 1983, earning them the Nobel Prize in 2008.
• Zidovudine was an early drug used in treating HIV.

HIV Transmission

• HIV is transmitted through infected body fluids.
• Sexual contact is a primary mode of transmission.
• Breast milk can transmit HIV to a developing fetus.
• HIV can also be transmitted via blood-contaminated needles.
• Organ transplants, artificial insemination, and blood transfusions are also potential transmission routes.
• Needle prick injuries can lead to HIV transmission.

Retrovirus

• HIV belongs to the Retroviridae family, a subfamily of lentiviruses.
• The genus includes HIV-1, HIV-2, and SIV.
• Retroviruses reverse transcribe their RNA genome into double-stranded DNA (dsDNA).

Anatomy of the AIDS Virus

• The virus has a lipid membrane, gp120 envelope protein, gp41 envelope protein, p17 matrix protein, p24 capsule protein, RNA, and reverse transcriptase.

Viral Genome

• LTR binds to host transcription factors for initiation of transcription.
• Vif overcomes APOBEC and prevents DNA degradation.
• Vpu promotes CD4 degradation and virus release.
• Vpr promotes G2 cell arrest.
• Rev promotes nuclear export of incomplete spliced viral RNA.
• Nef blocks apoptosis of CD4 cells and inhibits cellular activation.

HIV Origins

• HIV emerged from simian immunodeficiency viruses (SIVs).
• HIV-1 originated from chimpanzees, and HIV-2 originated from sooty mangabeys.
• Specific SIVs have crossed the species barrier to great apes and humans.

HIV Origins: Gorillas

• Gorillas may be a source of HIV.
• DNA analysis shows a significant match between an immune deficiency virus found in gorillas and humans.
• Transmission to humans likely occurred between 1884 and 1924.

Genetic Groups

• HIV-1 has three genetic groups: M (major), O (outlier), N (non O non M), P
• Group M is further divided into clades: A, B, C, D, F, G, H, J, K

HIV Types and Subtypes

• HIV-1 has multiple subtypes, a key component of its genetic diversity.
• HIV-1 group M consists of 9 subtypes and several circulating recombinant forms.

HIV Tropism

• HIV can infect T cells (T-tropic) and macrophages (M-tropic).
• CD4 is a key receptor for T-tropic HIV; CCR5 and CXCR4 are coreceptors.

HIV Affinity for CNS Cell Types

• HIV can infect microglial cells, astrocytes, and brain endothelial cells.
• These infections are not mediated via CD4.

HIV Genome Variability

• HIV's reverse transcriptase is error-prone, leading to high mutation rates, hence "quasi species."
• Viruses within an infected person are closely related, but not identical.

Global Summary of the AIDS Epidemic (2015)

• There were approximately 36.7 million people living with HIV in 2015.
• An estimated 2.1 million new HIV infections occurred in 2015.
• An estimated 1.1 million AIDS-related deaths occurred in 2015.
• Key statistics were provided for adults, women, and children.

HIV Pathogenesis: Early Events

• HIV transmission occurs via mucosal surfaces (vagina, rectum, urethra).
• HIV encounters mucosal dendritic cells on a susceptible CD4+ T cell.
• HIV replicates in CD4+ T cells and disseminates to lymph nodes and other tissues.
• This leads to a high viral load (viremia) and widespread infection.

HIV Pathogenesis: Gut-related Events

• Epithelial injury and depletion of mucosal CD4 cells occur during early infection.
• Microbial translocation increases lipopolysaccharide and activates TLR4.
• This results in a secretion of IL6 , contributing to chronic inflammation .

HIV Pathogenesis - Immune Pathogenesis

• Establishment of infection in gut-associated lymphoid tissue (GALT).
• Massive viremia and wide dissemination to lymphoid organs.
• Partial immunologic control of virus replication leading to chronic infection.
• Immune activation by cytokines and HIV envelope-mediated aberrant cell signaling.

HIV Dysfunction due to Immune Attacks

• Exhaustion of the T cell supply.
• Direct killing of T cells by the virus.
• Virus-induced apoptosis.
• Immunological senescence.
• Architectural destruction of lymphoid organs by fibrosis due to TGF-β.

HIV multiplication

• HIV binds to CD4 receptor of T-helper cells.
• HIV RNA is transcribed into T-cell genome, initiating reproduction.
• HIV multiplies inside CD4 cells, killing them, and causing reduced immunity.

Cellular & Humoral Immune Responses to HIV

• MHC class II-peptide complex activation of CD8+ cytotoxic T cells.
• CD4+ helper T cells release cytokines.
• B cells produce antibodies to neutralize the virus.

Immune Escape Strategies

• HIV employs various mechanisms to evade host immune responses.
• Neutralizing antibodies are thwarted by envelope protein variable loops.
• CD4+ and CD8+ T cells are targeted.
• Natural killer (NK) cells are impacted.

Natural History of HIV Infection

• The natural timeline of HIV infection shows stages, including an acute primary infection, a chronic asymptomatic phase, and progression to AIDS.

The Pathway of HIV Infection

• A diagram depicting the CD4+ T lymphocyte count and HIV RNA copies in the plasma throughout the disease progression.

HIV Infection Stages

• Stages based on HIV antibody testing, CD4 cell count, and clinical symptoms.
• Primary, asymptomatic, symptomatic, and AIDS.

HIV Testing

• ELISA, Western Blot, and rapid antibody tests for HIV diagnosis.
• Nucleic Acid Testing (NAT, using DNA-PCR), p24, and HIV viral co-culture are available.

HIV-2 Testing

• HIV-1 screening tests don't always detect HIV-2 infections.
• Combination tests exist to confirm HIV-2.
• Highly specific ELISAs, western blots, radioimmunoprecipitation assays, and polymerase chain reactions are useful.

Antiretroviral Treatment

• Different classes, including nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), are available.
• Combinations of drugs are frequently used.

Why No Cure for HIV

• The high mutation rate of HIV makes it difficult to develop a cure.
• HIV permanently incorporates into host DNA.
• Drug-resistant mutants evolve.

Issues in HIV Vaccine Development

• Lack of ideal animal models.
• High HIV-1 strain variability by subtypes
• Unfavorable market forces and difficult efficacy trials.

Opportunistic Infections

• Opportunistic infections are associated with HIV, particularly at low CD4+ T cell counts.
• Infections can be bacterial, viral, fungal, and parasitic.
• TB is commonly co-infected with HIV, often having a poor prognosis. (The first cause of mortality in patients infected with HIV.)

HIV Eclipse Phase

• The time between HIV infection and detectable HIV RNA in plasma.

HIV Window Period

• The time between HIV infection and detectable HIV antibodies in plasma.

Timeline of HIV Antibody Testing

• Baseline, 6 weeks, 12 weeks, 26 weeks after exposure , seroreversion is usually detected by 6 months.

Natural Course of HIV Infection

• Progressors with a median survival time of 10 years.
• Long-term non-progressors maintain stable CD4+ counts for a long time.
• Elite controllers have undetectable viremia despite lack of ART.

Inability to Eradicate HIV-1 Infection

• CD4+ T cell decline, inadequate CTL response, viral reservoirs (brain, lymphoid tissue), and latency in resting cells.
• HIV-1 has a high mutation potential, escaping immune responses and neutralizing antibodies.

This quiz covers the essential aspects of HIV infection, including its etiology, symptoms, and modes of transmission. Learn about the history of HIV, notable discoveries, and the methods of prevention and treatment. Test your knowledge on how HIV is acquired and the significance of using protective measures.