HIV Flashcards
HIV structure & classification
Family: Retroviridae
Subfamily: Lentiviridae
Genus: Lentivirus
2 segments of (+)ssRNA whose replication involves RNA-dependent DNA synthesis via reverse transcription.
Baltimore: VI
Capsid core with lipid enveloped derived from host.
Viral glycoproteins: gp120 surface and gp41 transmembrane.
HIV genes and proteins coded
- Structural proteins:
A. gag- Matrix, Capsid, Nucleocapsid
B. env- Surface envelope glycoproteins (gp 120) binds CD4
& Transmembrane envelope glycoprotein (gp 41)
C. pol - Rt, integrase, protease
- Regulatory proteins:
A. tat - trans-activator of transcription - transcription
B. rev - Regulator of virion protein expression - post transcriptional regulation and exposure of viral RNA from nucleus.
HIV subdivisions
HIV 1: 4 lineages M,N,O,P
M group divided into 9 subtypes: A,B,C,D,F,G,H,J,K
HIV 2: 9 lineages A to I
Most common HIV subtype globally
C - 42%
HIV CRF
Circulating recombinant form - hybrid of 2 subtypes
HIV life cycle
Infection of cells mediated by gp120 envelope glycoproteins.
Receptor- T cells have CD4 receptors - lymphocytes, monocytes, macrophages.
Other receptors used - CCR5 and CXCR4 - CCR5 inhibitors useful here.
Once HIV binds to CD4 + other receptors, gp41 fuses the virus and it enters into the cytoplasm - fusion inhibitors useful here.
In the CYTOPLASM, RNA undergoes reverse transcription to ssDNA and then to dsDNA. dsDNA forms a complex with the viral and host proteins and is transported to the nucleus.
dsDNA integrates into host genome by DNA splicing by viral integrase or forms DNA circles.
The integrated virus is called PROVIRUS. Transcription of viral RNA occurs by host RNA polymerase. Mature virions are assembled.
HIV protease is activated and is needed for viral maturation - encapsulation of the viral proteins.
Elite controller
A small subset of individuals exhibit persistently low plasma HIV RNA levels less than 50 copies/mL without ART.
High proportion of HLAb 5701 -65%- seen in this cohort - CD8 T cell driven viral control.
CD4 counts every 6 months & VL 6-12 months.
BHIVA recommends ART given low level viral replication if:
- Declining CD4
- Inverted CD4:8 ratio
- Any HIV related complications
- Coinfection with HBV,HCV, or HTLV
- Significant comorbidities including cancer
- Immunosuppression
- Pregnancy
Berlin & London patients
Underwent HSCT with a donor homozygous for delta 32 CCR5 mutations - leads to lack of CCR5 expression on cells.
Berlin patient has undetectable for 10 years - then started PrEP, so don’t know longer term outcome.
HIV testing window periods
Based on 99th percentile
4th gen - 45 days
3rd gen - 60 days
POCT - Determine HIV1/2 (3rd gen), INSTI HIV1/2, Oraquick Rapid HIV1/2 antibody test - 90 days
HIV screening assays timings
Infection - D0
RNA - D10
P24 capsid antigen - D14 to D20
IgM (EIA/CLIA) - D20 to D23
IgG (EIA/CLIA) - D28 onwards
HIV avidity
Offered by Colindale for suspected recent infections
HIV reporting
SEE ALBUM
HIV assay generations
1 through 5 - see ALBUM
HIV screening SMI algorithm
Diagnosis should be made on 3 CE (UKCA from 2025!) marked 4th gen assays in an ISO 15189 lab.
2 CE marked 4th gen test should detect HIV1/2 and a 3rd CE marked test should differentiate HIV 1 vs 2 (typing).
See ALBUM
HIV-1 usual regimens
Usual:
1. Dolutegravir (II)+ emtricitabine (NRTI)/tenofovir AF (NRTI) OR
Dolutegravir + emtricitabine/tenofovir DX
Bone/renal caveats for tenofovir DX
- Dolutegravir (II)/lamivudine (NRTI)
No baseline resistance, VL < 500k, CD4 > 200
- Dolutegravir (II)/lamivudine (NRTI)/abacavir (NRTI)
HLAB5701 negative and QRISK < 10%