Human immunodeficiency virus (hiv) :


#1

HUMAN IMMUNODEFICIENCY VIRUS (HIV) :
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:white_check_mark: LENTIVIRUS (slowly replicating RETROVIRUS) that causes the acquired immunodeficiency syndrome(AIDS)

:white_check_mark: a/k/a—“ Slim’s disease “ ( d/t weight loss)

:white_check_mark: Commonest secondary immunodeficiency disorder

:white_check_mark: Most patients with HIV infection progress to AIDS after a chronic phase lasting from 7 to 10 years.

:white_check_mark:Exceptions to this typical course are :-

  1. RAPID PROGRESSORS
    :heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
    chronic phase shortened to 2 to 3 years after primary infection.
    CD4T cell count < 200 /microL.

  2. LONG-TERM NON-PROGRESSORS.
    :heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
    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.
    :heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
    infected individuals have undetectable plasma virus (50-75 RNA copies/mL)

:white_check_mark:Most common mode of spread — (75% of all cases)Sexual contact ( most commonly from Male to female ).

:white_check_mark: Risk of transmission with needle stick injury— 0.3%.

:white_check_mark: Commonest cause of AIDS in children — Vertical transmission

:white_check_mark: BLOOD BANK and HIV ( Harrison18/e page no – 1513 ):-

:white_check_mark: Blood collected for transfusion is routinely screened for both HIV-1 and HIV-2

:white_check_mark:HIV transmission is by:
:traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light:

  1. whole blood
  2. packed rbc
  3. platelets
  4. leucocytes
  5. plasma

:white_check_mark:No-HIV –Transmission is seen with:
:traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light:

( Because 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

:white_check_mark:HIV Epidemiology:-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:cherry_blossom:HIV-1 ---- most common type a/w AIDS in the United States, Europe, and Central Africa
:cherry_blossom:HIV-2----- in West Africa and India.
:cherry_blossom: HIV-1 three subgroups

  1. M(major)
  2. O (outlier)
  3. N (neither M nor O)

:white_check_mark: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.

:white_check_mark: Most common cause of AIDS in India— HIV-1 group-M , Subtype-C.

:white_check_mark: life cycle of HIV:-

:cherry_blossom:HIV infects cells by using ---- CD4 molecule as receptor and various chemokine receptors as coreceptors.

:cherry_blossom:CD4 receptors are required for entry of HIV in Brain
a) macrophages /monocytes
b) dendritic cell
c) CD4T cells (worse affected cells)

:cherry_blossom: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.

:cherry_blossom:early in course of infection R5 (M-tropic) type of HIV is the dominant virus (90%).
:cherry_blossom:T-tropic viruses gradually accumulates ( R5 replaced by X4).

:cherry_blossom: 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) .

:cherry_blossom: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.

:white_check_mark:HIV and GENETICS:-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
:cherry_blossom: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

:cherry_blossom:high mutation rate of the human immunodeficiency virus (HIV) is due to host cell “DNA-POLYMERASE”

:white_check_mark:CD4 count and HIV:-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:cherry_blossom:Normal CD4 count ---- 500 cells/mm3 to 1,000 cells/mm3.

:cherry_blossom: Treatment is recommended for opportunistic infections at any level of CD4 count levels.

:white_check_mark: Viral load level of HIV in body) is measured by------- number of copies of HIV-1 per milliliter of blood plasma (copies/mL).

:white_check_mark:GOAL OF HIV-THERAPY ---- to lower viral load below 50 copies/mL within 6 months of treatment.

:white_check_mark:DIAGNOSES OF AIDS:-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
is made in anyone with HIV infection and a “CD 4-T cell count <200 /Microlitres.”
“AIDS-RELATED COMPLEX (ARC)”:-

:white_check_mark: Clinically recognized syndromes seen in HIV infected patients at the end of clinical latency

:white_check_mark:Clinical criteria to define ARC :-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

  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.

:white_check_mark: CD4 -COUNT SIGNIFICANCE :-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:cherry_blossom:During asymptomatic period of HIV infection, average rate of CD4T cell decline is —50 cells /mm3/year.
:cherry_blossom:High risk of opportunistic infections — CD4T cells < 200/mm3.
:cherry_blossom:Cardiovascular diseases risk — CD4T cells < 500/mm3.

:white_check_mark: CD4T-cells and infections :-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:cherry_blossom:> 350 cells/mm3 ---- HIV- associated dementia
:cherry_blossom:> 300 cells/mm3 – T.B.( Mycobaterium Tuberculosis)

:cherry_blossom:< 300 cells/mm3 –Thrush (Candidiasis); Oral hairy leukoplakia (EBV-infections );Protozoans (cryptosporidia; microsporidia and isospora belli)

:cherry_blossom:< 200 cells/mm3 ----Pnuemocystis Jirovecii (Carinii) Pneumonia (PCP); HIV –Associated Nephropathy ( HIVAN).; trypanosomiasis (Chagas disease); Toxoplasmosis; Lymphomas

:cherry_blossom:< 100 cells/mm3 – Cryptococcus neoformans; Bartonella henselae (Bacillary Angiomatosis);

:cherry_blossom:< 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

:white_check_mark:HIV- IMPORTANT-INFO:-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:cherry_blossom: Globally, Mycobacterium tuberculosis is
the most common opportunistic infection in HIV-infected individuals.

:cherry_blossom: Most common opportunistic infection in AIDS pneumonia — PNEUMOCYSTIS JIROVECI

:cherry_blossom: Most common opoortunististic infection in AIDS in INDIA— TUBERCULOSIS

:cherry_blossom:Most common FUNGAL infection in HIV/AIDS in INDIA/world both----- CANDIDIASIS

:cherry_blossom:Most common cancer in AIDS—NHL>>>> KAPOSI- SARCOMA

:cherry_blossom:Most common neurological manifestation in HIV infection— “AIDS-DEMENTIA COMPLEX”
:cherry_blossom:Most common skeletal muscle disorder ---- INFLAMMATORY MYOPATHY.
:cherry_blossom: Most common organism to cause pneumonia in HIV is---- streptococcus pneumonia (HARRISON 18/E PAGE 1547)

:white_check_mark:HIV and LYMPHOMAS:-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:cherry_blossom:Lymphoma occurs in HIV infection when CD4T CELL COUNT < 200 cells/mm3 .

:cherry_blossom:AIDS-DEFINING LYMPHOMAS are NON-HODGKINS LYMPHOMAS (NHL) only .(HODGKINS LYMPHOMA are not AIDS-DEFINING LYMPHOMAS).

:white_check_mark:AIDS-DEFINING NON HODGKINS LYMPHOMAS (NHL)-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

  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.

:white_check_mark:HIV associated HODGKINS LYMPHOMA :-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

  1. Mixed cellularity (most common)
  2. Nodular sclerosis
  3. Lymphocyte depleted

:white_check_mark:Most common type of lymphoma in HIV ----- (60%) IMMUNOBLASTIC LYMPHOMA ( diffuse large b cell lymphoma) .(Primary CNS Lymphoma – 20% in HIV cases.

:white_check_mark:Most common extranodal site for non hodgkins lymphoma in HIV ----CNS.

(Most common extranodal site for NON HODGKINS LYMPHOMA-------- stomach)

:white_check_mark:DIAGNOSIS OF HIV-INFECTIONS:-
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:

:cherry_blossom: Most sensitive (=best screening method)----- ELISA

:cherry_blossom: Most specific (=confirmatory)---- WESTERN BLOT (positive if antibodies exist against 2 out of 3 HIV-proteins i.e. p24; gp 41; gp120/60 )

:cherry_blossom:Window period ( 2-4 weeks)— by PCR.

:cherry_blossom:BEST METHOD for Diagnosis------RT-PCR