Sunday, 4 May 2014

HIV

high yield (HIV):
HUMAN IMMUNODEFICIENCY VIRUS (HIV) :
• LENTIVIRUS (slowly replicating RETROVIRUS)
that causes the acquired immunodeficiency
syndrome(AIDS)
• a/k/a---“ Slim’s disease “ ( d/t weight loss)
• Commonest secondary immunodeficiency
disorder
• Most patients with HIV infection progress to
AIDS after a chronic phase lasting from 7 to 10
years.
• Exceptions to this typical course are :-
1) RAPID PROGRESSORS
chronic phase shortened to 2 to 3 years after
primary infection.
CD4T cell count < 200 /microL.
2) LONG-TERM NON-PROGRESSORS.
untreated HIV-1-infected individuals who
remain asymptomatic for 10 years or more
with stable CD4+ T-cell counts and low levels
of plasma viremia (usually less than 500 viral
RNA copies per milliliter).
3) ELITE CONTROLLERS.
infected individuals have undetectable plasma
virus (50-75 RNA copies/mL)
• Most common mode of spread --- (75% of all
cases)Sexual contact ( most commonly from
Male to female ).
• Risk of transmission with needle stick
injury--- 0.3%.
• Commonest cause of AIDS in children ---
Vertical transmission
• BLOOD BANK and HIV ( Harrison18/e page no
– 1513 ):-
Blood collected for transfusion is routinely
screened for both HIV-1 and HIV-2
A) HIV transmission is by-------
1) whole blood
2) packed rbc
3) platelets
4) leucocytes
5) plasma
B) No-HIV –Transmission is seen with
( processing procedure will inactivate virus in all
given products) ---
1) hyperimmune gammaglobulin
2) hepatitis B immune globulin
3) plasma derived hepatitis B vaccine
4) Rh0 immune globulin
HIV Epidemiology:-
• HIV-1 ---- most common type a/w AIDS in
the United States, Europe, and Central Africa
• HIV-2----- in West Africa and India.
• HIV-1 three subgroups
1) M(major)
2) O (outlier)
3) N (neither M nor O)
• Group M ( subtypes or clades ;A to K ) ----
most common form worldwide
1) Subtype B --- most common in western
Europe and United States
2) Subtype E --- most common in Thailand.
3) Subtype C (fastest-spreading type
worldwide) --- most common in India, Ethiopia,
and Southern Africa.
• most common cause of AIDS in India---
HIV-1 group-M , Subtype-C.
life cycle of HIV:-
• HIV infects cells by using ---- CD4 molecule
as receptor and various chemokine receptors as
coreceptors.
• CD4 receptors are required for entry of HIV in
Brain
a) macrophages /monocytes
b) dendritic cell
c) CD4T cells (worse affected cells)
• Chemokine receptors:-
HIV isolates and their chemokine receptors:-
1) R5 strains use CCR5--- expressed on
monocytes / macrophage and T-cells both
2) X4 strains use CXCR4 --- expressed on T-
cells only.
3) R5X4-- dual-tropic.
early in course of infection R5 (M-tropic) type
of HIV is the dominant virus (90%).
T-tropic viruses gradually accumulates ( R5
replaced by X4).
T-tropic viruses are “MORE
VIRULENT” ( because capable of infecting many
T cells and even thymic T-cell precursors and
cause greater T-cell depletion and
impairment) .
• infection leads to low levels of CD4+ T cells
through a number of mechanisms including:
1) Apoptosis of uninfected bystander cells
2) Direct viral killing of infected cells
3) Killing of infected CD4+ T cells by CD8
cytotoxic lymphocytes that recognize infected
cells.
HIV and GENETICS:-
• Very high genetic variability ( difference from
other viruses) due to :-
a) Fast replication cycle with generation of
about 1010 virions every day
b) High mutation rate of approximately 3 x 10−5
per nucleotide base per cycle of replication and
c) Recombinogenic properties of REVERSE
TRANSCRIPTASE
• high mutation rate of the human
immunodeficiency virus (HIV) is due to host cell
“DNA-POLYMERASE”
CD4 count and HIV:-
• Normal CD4 count ---- 500 cells/mm3 to
1,000 cells/mm3.
• Treatment is recommended for opportunistic
infections at CD4 count levels:
1) less than 500/mm3 ----- ART start
2) Less than 200/ mm3---- pneumocystis
pneumonia (PCP).
3) Less than 50 mm3/: mycobacterium avium
complex (MAC).
• Some circumstances, it is recommended to
start treatment when CD4 count is higher.
These include:
a) hepatitis B or hepatitis C
b) heart problems or kidney disease
c) having treatment for cancer
d) age over 50
• Viral load (= level of HIV in body) is measured
by------- number of copies of HIV-1 per
milliliter of blood plasma (copies/mL).
• GOAL OF HIV-THERAPY ---- to lower viral
load below 50 copies/mL within 6 months of
treatment.
• DIAGNOSES OF AIDS:-
is made in anyone with HIV infection and a “CD
4-T cell count <200 /Microlitres.”
“AIDS-RELATED COMPLEX (ARC)”:-
• Clinically recognized syndromes seen in HIV
infected patients at the end of clinical latency
• Clinical criteria to define ARC :-
1) Generalised lymphadenopathy (>2 non
inguinal sites)
2) Fatigue /malaise
3) Weight loss ( > 7kg or >10% of normal body
weight)
4) Fever
5) Diarrhoea
6) Night sweats
NOTE:- OPPORTUNISTIC INFECTIONS and
CANCERS a/w AIDS are not included in this
criteria.
CD4 -COUNT SIGNIFICANCE :-
• During asymptomatic period of HIV infection,
average rate of CD4T cell decline is ---50
cells /mm3/year.
• High risk of opportunistic infections --- CD4T
cells < 200/mm3.
• Cardiovascular diseases risk --- CD4T cells <
500/mm3.
• CD4T-cells and infections :-
1) > 350 cells/mm3 ---- HIV- associated
dementia
2) > 300 cells/mm3 – T.B.( Mycobaterium
Tuberculosis)
3) < 300 cells/mm3 –Thrush (Candidiasis); Oral
hairy leukoplakia (EBV-infections );Protozoans
(cryptosporidia; microsporidia and isospora
belli)
4) < 200 cells/mm3 ----Pnuemocystis Jirovecii
(Carinii) Pneumonia (PCP); HIV –Associated
Nephropathy ( HIVAN).; trypanosomiasis
(Chagas disease); Toxoplasmosis; Lymphomas
5) < 100 cells/mm3 – Cryptococcus
neoformans; Bartonella henselae (Bacillary
Angiomatosis);
6) < 50cells /mm3--- Cytomegalovirus (CMV-
retinitis); Mycobaterium Aviam Complex (MAC);
Histoplasmosis; IRIS (Immune Reconstitution
Inflammatory Syndrome ---parodoxical
worsening of preexisting symptoms after
starting ART treatment ); Primary CNS
Lymphomas
HIV- IMPORTANT-INFO:-
1) Most common opportunistic infection in
AIDS---- PNEUMOCYSTIS JIROVECI
2) Most common opportunistic infection in AIDS
pneumonia --- PNEUMOCYSTIS JIROVECI
3) Most common opoortunististic infection in
AIDS in INDIA--- TUBERCULOSIS
4) Most common FUNGAL infection in HIV/AIDS
in INDIA/world both----- CANDIDIASIS
5) Most common cancer in AIDS---KAPOSI-
SARCOMA
6) Most common neurological manifestation in
HIV infection--- “AIDS-DEMENTIA COMPLEX”
7) Most common skeletal muscle disorder ----
INFLAMMATORY MYOPATHY.
8) Most common organism to cause pneumonia
in HIV is---- streptococcus pneumonia
(HARRISON 18/E PAGE 1547)
HIV and LYMPHOMAS:-
• Lymphoma occurs in HIV infection when CD4T
CELL COUNT < 200 cells/mm3 .
• AIDS-DEFINING LYMPHOMAS are NON-
HODGKINS LYMPHOMAS (NHL) only .
(HODGKINS LYMPHOMA are not AIDS-
DEFINING LYMPHOMAS).
• AIDS-DEFINING NON HODGKINS LYMPHOMAS
(NHL)-
1) Immunoblastic lymphomas (60%--Most
common Lymphoma in HIV)---consists of –a)
diffuse large b cell lymphoma b) primary
effusion lymphoma
2) Burkitts lymphomas (small non cleaved cell
lymphomas)
3) Primary CNS lymphomas.
• HIV associated HODGKINS LYMPHOMA :-
1) Mixed cellularity (most common)
2) Nodular sclerosis
3) Lymphocyte depleted
• Most common type of lymphoma in HIV -----
(60%) IMMUNOBLASTIC LYMPHOMA ( diffuse
large b cell lymphoma) .(Primary CNS
Lymphoma -- 20% in HIV cases (HARRISON 18/
e page 1566.)
• Most common extranodal site for non
hodgkins lymphoma in HIV ----CNS.
(Most common extranodal site for NON
HODGKINS LYMPHOMA-------- stomach)
DIAGNOSIS OF HIV-INFECTIONS:-
• Most sensitive (=best screening method)-----
ELISA
• Most specific (=confirmatory)---- WESTERN
BLOT (positive if antibodies exist against 2 out
of 3 HIV-proteins i.e. p24; gp 41; gp120/60 )
• Window period ( 2-4 weeks)--- by PCR.
Compiled by Devesh Mishra sir

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