Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome (AIDS)
Human Immunodeficiency Virus (HIV) & Acquired Immune Deficiency Syndrome (AIDS) Part I
The Uniqueness Of AIDS
AIDS is a new disease to humans and society.
Originated from mutation(s) of a virus common to another species.
HIV/AIDS has changed the tropisms of several pathogens common to humans, including imparting neurological tropisms.
Allowed the reemergence of pathogens in humans that were nearly eradicated.
Continues to demonstrate the role of cellular immunity in the evolution of several human diseases.
Current State of AIDS Treatment
No adequate treatment exists for the eradication of the AIDS virus in individuals already infected with HIV.
There is an increasing population of persons who remain infectious.
No vaccine is currently available to protect against HIV infection or AIDS.
Common Clinical Observations
All patients with AIDS exhibit a severe depression of cellular immunity.
Hypothesized Risk Factors for AIDS
Various possibilities considered:
A new disease within the gay community possibly linked to
Use of recreational drugs (e.g., nitrates) to heighten sexual experience?
Practice of anal sex?
Combination of multiple factors associated with the gay lifestyle?
Emergence of a new strain of cytomegalovirus.
A fungus producing cyclosporin A.
The AIDS Virus: Designation History
Previous designations:
Lymphadenopathy-associated virus (LAV)
AIDS-related virus (ARV)
Human T-cell lymphotropic virus type 3 (HTLV-3)
Current designation: Human Immunodeficiency Virus (HIV).
Evidence Supporting HIV as the Etiologic Agent of AIDS
Overwhelming evidence indicates that HIV is the causative agent of AIDS.
Animal and Epidemiologic Studies of HIV/AIDS
Animal studies:
Similar retroviruses causing immunodeficiency identified in animals:
Feline immunodeficiency virus
Simian immunodeficiency virus
Epidemiologic studies:
AIDS manifests clinically only after HIV infection presents.
HIV can be detected and/or isolated from 100% of patients diagnosed with AIDS.
HIV cannot be detected in patients who are immunosuppressed due to drugs, X-irradiation, or cancers.
Blood-Transmission Studies
Studies from 1982 and 1983 revealed a direct correlation between HIV infection in donors and subsequent development of AIDS in recipients.
Dramatic decreases in transfusion-associated AIDS have occurred since screening blood for HIV infection.
In Vitro Studies
In vitro, HIV infects and kills CD4+ T lymphocytes in culture, correlating with the affected cell population in AIDS.
Koch’s Postulates
Four postulates to establish a microorganism as the causative agent of a disease:
The microorganism must always be found in diseased individuals, never in healthy individuals.
The microorganism must be cultivated in pure culture.
Pure cultures must cause the same disease when inoculated into susceptible animals.
The microorganism must be re-isolated from the experimentally infected animal.
Application to HIV/AIDS:
HIV is found exclusively in persons with AIDS, not in immunosuppressed individuals.
HIV has been isolated from AIDS patients and cultivated in pure form.
Researchers accidentally inoculated with pure cultures of HIV have developed AIDS.
Identical strains of HIV have been recovered from researchers post-inoculation.
Global Statistics on HIV/AIDS
Since the onset of the pandemic, approximately 91.4 million individuals have been infected with HIV.
Of those infected, 44.1 million have died from AIDS-related illnesses.
Initial mortality rate estimated between 100% (83%-90%).
2009 mortality rate estimated between 52% to 73%.
Current mortality rate approximates ~48%.
Current Global Statistics (2024)
40.8 million individuals are currently living with HIV infection.
87% of individuals living with AIDS are aware of their HIV status.
5.3 million individuals are unaware they have HIV.
1.3 million new infections reported.
AIDS-related deaths have decreased by 70% since the peak in 2004.
In 2024, there was a death attributable to HIV-related causes approximately every minute.
US Statistics (2022)
Approximately 1.2 million individuals living with HIV infection.
13% of individuals living with AIDS are unaware of their infection.
31,800 new infections reported.
Nature of HIV
HIV is classified as a pathogenic human retrovirus.
Characteristics of Retroviruses
Retroviruses possess reverse transcription capabilities.
Virion structure:
Enveloped
Icosahedral or conical capsid
Envelope acquired at the plasma membrane.
Contains reverse transcriptase enzyme.
Diameter approximately 100 nm.
Genome is linear single-stranded RNA between 7 - 10 kilobases.
Encodes for 9 structural and regulatory proteins.
Distinctive Characteristics of Retroviruses
Contains two identical copies of the RNA genome per virion.
Genome RNA gets converted to DNA by reverse transcriptase.
A DNA copy of the genome (provirus) integrates into host cell DNA.
Classification of HIV
Among retroviruses, HIV is classified specifically as a lentivirus.
Types of HIV
HIV Type 1 (HIV-1):
Prevalent globally.
Causes slow but progressive immune system deterioration (5 - 8 years).
HIV Type 2 (HIV-2):
Found primarily in West Africa.
Causes slow but progressive immune system deterioration (11 - 19 years).
HIV-1 Subtypes (Clades)
Subtype nomenclature for classification of HIV-1 isolates is based on genetic diversity.
Specific geographical areas cluster certain subtypes.
Major (M) group: contains 9 subtypes (A-D, F-H, J, K).
B subtype is predominant in the United States and Europe.
Recognized groups: Outlier (O) group, non-M, non-O (N) group, and P group.
Global Considerations for Vaccine Development
Existence of subtypes worldwide must be taken into account in developing safe and effective AIDS vaccines.
HIV-1 Genome Segments
gag (group-specific antigen):
Composition: capsid protein, matrix protein, nucleocapsid protein.
pol (DNA polymerase):
Includes: reverse transcriptase, protease, integrase.
env (envelope proteins):
Includes: gp120, gp41, and gp160 (precursor).
Lentivirus Genome Composition
gag (group-specific antigen)
pol (DNA polymerase)
env (envelope proteins)
Additional regulatory genes: vif, vpu, tat, rev, nef, vpr.
Receptors & HIV Tropisms
T-cell-tropic strains of HIV-1:
Utilize CD4 molecule and CXCR4 chemokine receptor.
Macrophage-tropic strains of HIV-1:
Utilize CD4 molecule and CCR5 chemokine receptor.
Function of Reverse Transcriptase
Functions as three enzymes:
RNA-dependent DNA polymerase: Uses single-stranded RNA as a template to form single-stranded DNA copy of genome.
RNAse H activity: Selectively dissolves RNA in RNA-DNA hybrid.
DNA-dependent DNA polymerase: Uses the single-stranded DNA copy to form a double-stranded DNA copy (provirus or proviral DNA).
Maturation of HIV-1
Full-length transcripts from proviral DNA serve as genomic RNA.
env protein (gp160) undergoes glycosylation in the lumen of the ER, where it is cleaved into gp120 and gp41, then directed to plasma membrane.
gag and pol proteins bind to the inner surface of the plasma membrane and newly synthesized genomic RNA.
As assembly around genomic RNA occurs, the plasma membrane curves, allowing the developing virion to grow.
Final Assembly and Release of HIV-1
Spherical particles are formed and enveloped through the envelopment process.
Released enveloped particles undergo protease cleavage of gag and pol polyproteins to yield individual structural and enzymatic proteins.
Structural proteins rearrange to form the viral core of mature, infectious virions.
Susceptibility to HIV-1 Infection
HIV-1 does not discriminate based on:
Sex (male vs female)
Age (infant vs elderly)
Race or Ethnicity
Socioeconomic Status
Geography
Religion
Sexual Preference
Equal Susceptibility
Everyone has equal susceptibility to HIV-1 infection; however, not all individuals are equally susceptible to developing AIDS following HIV-1 infection.
Transmission of HIV-1
Transmission occurs through direct contact with infected body fluids (not transmitted via aerosols).
Body Fluids Infected with HIV-1
Blood and blood products.
Semen and cervicovaginal secretions.
Amniotic fluid.
Breast milk.
Saliva.
Tears.
Urine.
Cerebrospinal fluid.
HIV-1 is not detected in sweat.
Casual Contact and Transmission
HIV-1 is not transmitted through casual contact, including:
Handshaking.
Hugging.
Kissing on the cheek.
Deep kissing (uncertain).
Sharing household items.
Toilet seats, doorknobs, hot tubs.
Routes of HIV-1 Transmission
Sexual route
Blood route
Mother to child route
Sexual Route of HIV-1 Transmission
Risk levels for HIV-1 transmission during sexual activities (from highest to lowest risk):
Anal intercourse.
Vaginal intercourse.
Oral sex (risk level uncertain).
Cofactors Increasing Susceptibility to HIV-1 Infection
Genital lesions from other sexually transmitted diseases (gonorrhea is a possible exception).
Lack of circumcision among males increases susceptibility to:
Genital herpes.
Genital warts.
No increased susceptibility to syphilis.
Alcohol consumption.
Blood Route of HIV-1 Transmission
Transfusion of blood or blood products.
Sharing of contaminated needles (not solely from drug abuse).
Transplantation of contaminated tissues or organs.
Occupational Transmission of HIV-1
Accidental needlestick has a transmission risk of 0.1 - 0.3% if blood is known to be HIV-1 positive.
If blood status is unknown, risk varies by prevalence in the community:
Prevalence at 1:10,000 yields a risk of 1:10 million.
Prevalence at 1:100 yields a risk of 1:100,000.
Transmission likelihood depends on multiple factors, including needle bore, depth of needlestick, volume injected, and viral load.
Comparison: HIV-1 vs Hepatitis B Virus (HBV) Transmission Risk
Risk of infection from a single needlestick:
HIV-1: <0.5% (if known to be HIV+)
HBV: ~18% (if known to be HBV+)
Mother-to-Child Route of HIV-1 Transmission
Transmission rate ranges from 12% to 50% (average = 25%).
Intrauterine transmission occurs via the placenta.
Virus exposure at birth can happen during vaginal delivery.
Breastfeeding can lead to transmission through infected breast milk, with a ~12% risk for extended breastfeeding.