HIV: Human Immunodeficiency Virus

HIV: Human Immunodeficiency Virus

• HIV is a retrovirus that attacks immune cells, specifically those with a CD4 surface marker, including LTCD4+, monocytes, macrophages, and dendritic cells.
• This attack weakens the body's immune system.
• HIV can spread through sexual transmission, blood contact, or from mother to fetus.

HIV Types

• HIV-1 is the most common type worldwide and is largely responsible for the global pandemic.
• HIV-2 is more commonly found in West Africa.

Global Impact

• According to UNAIDS data from 2022, 39 million people globally are living with HIV.
• HIV infections are increasing year by year.

Diagnosis and Treatment

• HIV diagnoses are often delayed.
• Without treatment, HIV can progress to AIDS, leading to opportunistic infections.
• Optimal management involves antiretroviral therapy (ART or ARV).
• Challenges exist, including treatment failures and insufficient sensitization programs.

Viral Taxonomy

• Order: Ortervirales
• Family: Retroviridae
• Subfamily: Orthoretrovirinae
• Genus: Lentivirus
• Species: Human Immunodeficiency Virus
• Types: HIV-1 (most common) and HIV-2
• Groups: M, N, O, and P for HIV-1; A to I for HIV-2
• Subtypes: Various subtypes exist for each group.

Viral Structure

• Spherical shape, ranging from 90 to 120 nm in diameter.
• Envelope: A lipid bilayer derived from the host cell and contains spicules.
• Spicules: Consist of Surface Glycoprotein (GP120 for HIV-1/GP105 for HIV-2) and Transmembrane Glycoprotein (GP41 for HIV-1/GP35 for HIV-2).
• Matrix Protein: P17 (HIV-1) or P16 (HIV-2). These are external proteins associated with viral protease.
• Capsid Protein: P24 (HIV-1) or P26 (HIV-2). These are internal and contain the genome.
• Nucleocapsid Proteins: P6-P7 (HIV-1) or P6-P8 (HIV-2). These are associated with viral RNA.
• Enzymes: Reverse transcriptase, integrase, and protease.

Viral Genome

• Consists of two identical strands of single-stranded RNA with positive polarity.
• Three main genes: gag, pol, and env.
  • gag: codes for structural proteins (capsid, matrix, nucleocapsid).
  • pol: codes for enzymes (reverse transcriptase, protease, integrase).
  • env: codes for envelope glycoproteins, specifically gp160, which is cleaved into gp120 (surface) and gp41 (transmembrane/fusion).
• Six regulatory genes contribute to the virus's pathogenicity.
• There are two redundant terminal sequences involved in regulating viral transcription and integration.

Genetic Variability

• High genetic variability in HIV occurs due to:
  • Frequent random mutations: Errors during reverse transcription due to lack of error correction.
  • Recombination: Infection by two genetically distinct virions, leading to recombinant forms.
  • Selection of strains: pressures of the immune system and antiviral treatments.
• This results in a viral population comprised of genetically different, closely related viruses called quasi-species.
• This high variability contributes to the virus's intra-individual diversity.

Epidemiology: Transmission and Prevalence

• Reservoir: Humans
• Transmission routes include:
  • Sexual contact: High-risk with other STIs present.
  • Blood exposure: Through transfusions, accidental exposures (AES), sharing needles, unsanitized piercing/tattoo equipment.
  • Mother-to-child: During the third trimester, perinatally, and via breastfeeding.
• Geographic distribution:
  • HIV-1 group M has pandemic status and is ubiquitous.
  • HIV-2 is more localized in West Africa.
• Susceptibility: Complete, due to the absence of protective immunity.

Epidemiology: Global and National Statistics

• Global AIDS Monitoring by UNAIDS in 2022:
  • 39 million people were living with HIV.
  • 1.3 million new HIV infections occurred.
  • 630,000 deaths were related to AIDS.
• In Morocco, as reported by the Ministry of Health and Social Protection in 2022:
  • 21,200 people were living with HIV.
  • 21% of people living with HIV were unaware of their serological status.
  • 760 new HIV infections were reported.
  • Most cases were concentrated in Souss-Massa, Casablanca-Settat, and Marrakech-Safi.

Pathophysiology

• Target Cells: HIV targets LT CD4+, monocytes/macrophages, and dendritic cells.
• Impact on LT CD4+: Leads to a lethal cytopathic effect (CPE) and cell death.
• Role of Monocytes/Macrophages: These cells support viral presence without damage, acting as viral reservoirs and vehicles.
• Three phases of infection are: Primary infection, asymptomatic phase, and AIDS.

Viral Replication

• There are 3 phases in the viral replication.
• Stage 1: Viral replication is intense, leading to a destruction and decrease in the rate of LT CD4+ blood
• Stage 2: immune response is adaptive. LTCD8 and plasmocytes will secrete antibodies, this will lead to the augmentation of LTCD4 and the diminuation of the viral count.
• Stage 3: Decrease of LTCD4, destroyed by LTCD8 leading to lymphopenia CD4+ and an increase to CD4/CD8 In the last stage, the secretion of the LTCD4 is too low to combat the multiplication and differentiation of LT8 and LB. This results in the reduction of LT8 and plasmocyctes which increases CV.

Clinical Manifestations

• Acute Infection (PI): Occurring 10-12 days after exposure, lasting weeks.
  • 50% asymptomatic -50% show signs of fever, swollen glands, sore throat, rash, meningitis, or mono.
• Latent Phase: occurs after PI with duration lasting 10 years.
  • Asyptomatic and can have minimal symptoms
  • LCD4 decreases by 30-100 Cells per mm3 per annum
  • AIDS occurs 2-10 years
• AIDS Phase: 10 years after PI, usually lasts 2-3 years
  • Immune system diminishes
  • Manifestations can occur from:
    • Pneumocystose, neurological issues, CMV
    • sarcomas and lymphomas

Diagnostic Contexts

• Mandatory screening for blood, organ, and tissue donations, as well as sperm.
• Pregnancy
• Following accidental exposures (AES).
• For STIs

Biological Diagnosis: Sampling

• Patient consent is mandatory.
• Serology: Venous blood samples collected in a dry tube will yield serum.
• Molecular biology: Venous blood collected in an EDTA tube will yield plasma samples.
• Other samples: can be obtained from cerebral spinal fluid and sperm.
• Storage: Samples are to be frozen at -20°C if immediate testing is not possible; it can be kept for a year.

Analytical Phase

• Screening Tests
• Elisa 4 tests can determine HIV1 and HIV2
• Diagnostic testing to identify any risk
• Confirmation must be done with a Western Blot

ELISA vs TROD

• ELISA takes longer to detect, where TROD give more immediate results regarding the screening.
• For the 4th generation for ELISA, the window is limited to two weeks as the AG p24 shows up. Where only antibodies take as one is three weeks to detect.
• ELISA takes longer, where TROD can take up to 20 minutes.
• ELISA tests are considered harder to perform outside of the laboratory as machines for ELISA are seen as complex.
• If patient has had potential risk less than 1 month prior to testing, TROD may not determine a result and is better for results.

Tests for HIV: PCR

• RT PER (Real Time)
• ARN Virial can detect as early s 7-10 days
• Viral detection as low as 20-40 copies
• Aids in diagnosing PI and the patient's genetic code to determine treatment options
• Can also determine the evolution of the disease and any reactions

Methods for Confirming

• Tests use the Western Blot.
• Composed of ag viraux that is used to see migration of gel in order to determine weight.
• Can determine difference between VIH 1 and 2
• Though, it is an expensive method.

Testing During Pregnancy

• Detect HIV in women that are pregnant
• Find and treat infections.
• Treat new infections

Current Testing

• PCR helps determine new borns with ADN directly
• Normal rhythm is 1-3-6-9 months for diagnosis
• Confirmation comes with 2 rounds of tests.

Prevention

• Proviral can be determined using Viral detection.
• But : Quantification du réservoir viral • Diagnostic d’ infection latente du VIH avec charge virale indétectable • Prédictif du risque de progression rapide de l’infection • Non recommandé actuellement en pratique courante • Détection de l’Antigénémie p24 : • Ag p24= Ag soluble de capside VIH 1 • Intérêt actuel : Diagnostic de PI avant la séroconversion Ac = Détectable ≈ 15 jours après

Resistance

• Reccomended before treatment and after failure
• Sequences help determine virus and ARV codes
• Echec if genotype cannot process the >500. ML

Treament

• After 6 months
  • CV undetectable.
  • Lymph reaches TCD4
  • Death rates lower
  • Prevention happens from the start

Prevention

• Six classes exist and are not as effective.
• Tested in March 2015 - treatment is reccomended by OMS
• ARV helps quickly
  • Three types determine:
    • INI InNTI
    • Inti III
    • Inti 1 p1

Monitoring

• Immuno helps, to make any adjustments
• Charge measures viral detection to do flow of cyto.
• Rates must be done with table 1 CD4
  • M0 1x pAN
  • 350 and is indetectable

Failed Theapy

• Charge has low or no impact and is caused by:
• Selection will fail if no cause it apparent by testing.
• Thereoay has tests results such as ARY and genotypes