2: HIV Infection Flashcards

Question

HIV epidemiology

Answer 1

A

HIV2 less virulent and harder to transmit

Answer 2

A

retrovirus
RNA = replicated inside a cell using RT to convert RNA to DNA to be integrated into host genome

Structure:

icosahedral (20-faced)
diploid genome
9 genes that encode 15 structural, regulatory and auxiliary proteins i.e. gp120, gp41, RT

Answer 3

A

CD4+ Th, CD4+ monocytes, CD4+ dendritic cells

selective loss of CD4 Th cells

Protection from HIV requires:

antibodies (B cells)
sufficient CD8+ T cells

Answer 4

A

Receptor = CD4 molecule/antigen

Co-receptor (most strains require) = CCR5 / CXCR4

Answer 5

A

Sexually = via mucosa (esp. damaged sites/MSM), infects CD4 cells which carry virus to LN

Infected blood = transfusion, needle sharing, blood products

Vertical (mother to child) = ante/intrapartum, breastmilk

Answer 6

A

inflammation
nonspecific activation of macrophages, NK cells and complement
release of cytokines and chemokine (only those made by NK cells can reduce infection of CD4 T cells by HIV)
stimulation of plasmacytoid dendritic cells (pDC) by TLRs

Answer 7

A

Anti-gp120 and anti-gp41 (Nt) antibodies are important in protective immunity
Non-neutralising anti-p24 gag IgG are also produced
HIV remains infectious even when coated with antibodies

Answer 8

A

Reverse Transcriptase (RNA to DNA) – lacks proof-reading mechanisms from cellular DNA polymerases
Transcription of DNA into RNA copies

→ accumulate lots of mutations with numerous variants

The propensity to mutate can lead to the development of advantageous features such as:

Escape from neutralising antibodies
Escape from HIV-1 specific T cells
Resistance and escape from antiretroviral drugs

Answer 9

A

Attachment (Attachment Inhibitors / AI)
Fusion (FI)
Reverse transcription (RTI)
Integration of viral DNA into host (INI)
Transcription of DNA to viral RNA
Translation of viral RNA to produce viral proteins
Viral protein cleavage by proteases (PI)
Assembly and budding of new HIV

-gravir = integrase inhibitor

-avir = protease inhibitor

-ines = NRTI

Answer 10

A

HIV to AIDS = 8-10 years

viral burden predicts disease progression:

rapid progressors (10%) take 2-3 years (mainly seen in Africa)
LTNP (<5%) will have stable CD4+ counts and no sx’s after 10 years
Exposed-seronegatives (ESN) = people exposed to HIV but do not seroconvert
Elite Controllers = can suppress viral replication

HAART significantly improves prognosis

Answer 11

A

Anti-HIV antibodies (ELISA) – screening test

Anti-HIV antibodies (Western Blot) – confirmation test

Viral load (viral RNA detection using PCR) – very sensitive; steps:

Reagent preparation
Specimen preparation
Amplification
Detection

Initial baseline plasma viral load is a good predictor of the time taken for the disease to appear

Answer 12

A

Flow cytometry

Onset of AIDS correlated with decrease in number of CD4 T cells

antigens on T cells:

CD3,CD4
CD19
CD8
CD56

Answer 13

A

(1) Phenotypic → viral replication is measured in cell cultures under selective pressure of increasing concentrations of antiretroviral drugs (compared to wildtype)
(2) Genotypic → mutations detected by sequencing amplified HIV genome (limited to sequencing RT and P)

Both assays are available commercially (but are EXPENSIVE)

Answer 14

A

Substantial control of viral replications

Increase in CD4+ T cell counts

initial rise = redistribution of memory T cells
later rise = thymic naive T cell creation

Improvement in host defences (decline in opportunistic infections (AIDS) and mortality)

NOTE: HAART does NOT eliminate HIV from the body as there is a reservoir in CD4+ T cells

Answer 15

A

Combination of 3 or more ART drugs

2 backbone drugs (x2 NRTIs)
>1 binding agent (x1 NNRTI or INI), 2nd line = boosted PI

Answer 16

A

Backbone drugs:

Nucleoside Reverse Transcriptase Inhibitors (NRTI) – e.g. Zidovudine / AZT
Nucleotide RTI – e.g. Tenofovir
Non-NRTI (NNRTI) – e.g. Efavirenz
Protease inhibitor (PI) – e.g. Indinavir

Binding agents:

Integrase inhibitors (INI) – e.g. Raltegravir
Attachment inhibitors (AI) – e.g. Maraviroc
Fusion inhibitors (FI) – e.g. Enfuvirtide

Answer 17

A

All symptomatic patients
All CD4+ count < 200 cells/uL
CD4 count 200-350 cells/uL

All offered IMMEDIATE treatment – more for _public health_ than an individual’s health

Answer 18

A

Boosted PI – block cytochrome P450
Efavirenz – P450 inducer
INI – interacts with indigestion remedies (Gaviscon, aluminium salts, calcium salts) and is sequestered which can be very bad as some INI is absorbed but very little and so resistance is bred very quickly

I.E. if treating >55yo HTN with amlodipine, the amlodipine will seem to not work if the patient is also on Efavirenz (they might not tell you this) as the amlodipine will be broken down too quickly

Answer 19

A

Does NOT eradicate latent HIV-1
Fails to restore HIV-specific T cell responses
Threat of drug resistance
Significant toxicities
High pill burden
Adherence
Quality of life
Cost (>40% with no access)

Answer 20

A

Male circumcision (APCs in foreskin at a high density)
Condoms
PrEP (Truvada)
TasP (Treatment as Prevention – if on treatment, cannot transmit infection; i.e. U=U)

Answer 21

A

HIV-1 infection interferes with basic aspects of CD4+ and CD8+ T cell activation
HIV-1 infection may interfere with APC function
Effective immunity requires antibodies to prevent infection and neutralise virus, and sufficient CTL to eliminate latently infected cells
An effective vaccine must elicit potent antibodies and CTL
Permanent control of latently infected cells by CTL may prevent progression to AIDS
Effective ART requires combinations of at least 3 agents, typically from different classes
Arrest of viral replication does not lead to diminution of latently infected cells; thus a residual reservoir persists which his capable of establishing ongoing viral activity upon therapy discontinuation
Host immune responses may reduce this risk of even deplete residual reservoirs