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 :-
chronic phase shortened to 2 to 3 years after primary infection.
CD4T cell count < 200 /microL.
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).
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
HIV transmission is by:
- whole blood
- packed rbc
No-HIV –Transmission is seen with:
( Because processing procedure will inactivate virus in all given products):-
- hyperimmune gammaglobulin
- hepatitis B immune globulin
- plasma derived hepatitis B vaccine
- Rh0 immune globulin
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
- O (outlier)
- N (neither M nor O)
Group M ( subtypes or clades ;A to K ) ----most common form worldwide
- Subtype B — most common in western Europe and United States
- Subtype E — most common in Thailand.
- 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)
HIV isolates and their chemokine receptors:-
- R5 strains use CCR5— expressed on monocytes / macrophage and T-cells both
- X4 strains use CXCR4 — expressed on T-cells only.
- 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:
- Apoptosis of uninfected bystander cells
- Direct viral killing of infected cells
- 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 any level of CD4 count levels.
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 :-
- Generalised lymphadenopathy (>2 non inguinal sites)
- Fatigue /malaise
- Weight loss ( > 7kg or >10% of normal body weight)
- 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 :-
> 350 cells/mm3 ---- HIV- associated dementia
> 300 cells/mm3 – T.B.( Mycobaterium Tuberculosis)
< 300 cells/mm3 –Thrush (Candidiasis); Oral hairy leukoplakia (EBV-infections );Protozoans (cryptosporidia; microsporidia and isospora belli)
< 200 cells/mm3 ----Pnuemocystis Jirovecii (Carinii) Pneumonia (PCP); HIV –Associated Nephropathy ( HIVAN).; trypanosomiasis (Chagas disease); Toxoplasmosis; Lymphomas
< 100 cells/mm3 – Cryptococcus neoformans; Bartonella henselae (Bacillary Angiomatosis);
< 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
Globally, Mycobacterium tuberculosis is
the most common opportunistic infection in HIV-infected individuals.
Most common opportunistic infection in AIDS pneumonia — PNEUMOCYSTIS JIROVECI
Most common opoortunististic infection in AIDS in INDIA— TUBERCULOSIS
Most common FUNGAL infection in HIV/AIDS in INDIA/world both----- CANDIDIASIS
Most common cancer in AIDS—NHL>>>> KAPOSI- SARCOMA
Most common neurological manifestation in HIV infection— “AIDS-DEMENTIA COMPLEX”
Most common skeletal muscle disorder ---- INFLAMMATORY MYOPATHY.
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)-
- Immunoblastic lymphomas (60%–Most common Lymphoma in HIV)—consists of –a) diffuse large b cell lymphoma b) primary effusion lymphoma
- Burkitts lymphomas (small non cleaved cell lymphomas)
- Primary CNS lymphomas.
HIV associated HODGKINS LYMPHOMA :-
- Mixed cellularity (most common)
- Nodular sclerosis
- Lymphocyte depleted
Most common type of lymphoma in HIV ----- (60%) IMMUNOBLASTIC LYMPHOMA ( diffuse large b cell lymphoma) .(Primary CNS Lymphoma – 20% in HIV cases.
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.
BEST METHOD for Diagnosis------RT-PCR