Long-term non-progressors

Medicoman · July 10, 2020, 11:21am

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 :-

RAPID PROGRESSORS

chronic phase shortened to 2 to 3 years after primary infection.

CD4T cell count < 200 /microL.

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).

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

HIV transmission is by:

whole blood
packed rbc
platelets
leucocytes
plasma

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 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

M(major)
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)

Chemokine receptors:-

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)
Fever
Diarrhoea
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

HIV- IMPORTANT-INFO:-

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

#drdeveshmishra

#DPMA #Highyieldinfo: