CHAPTER 173 AIDS/HIV
-HIV- retrovirus
-fourth leading cause of mortlity worldwide
-sixth leading cuse of death of Americans age 25 to 44
Virion- icosahedral struc
- 2 envelope proteins- external gp120 and
transmembrane gp41
Hallmark: reverse transcription of of its genomic RNA to
DNA by enzyme reverse transcripatase
CD4 molecule- responsible for helper or inducer fxn in the
immune sysytem
- two major coreceptor HIV 1- CCR5 and CXCR4
Cellular activation_ critical to the pathogenesis of HIV
disease
gag- encodes proteins that forms the core of the virion -
p24 ag
pol- encodes enzyme for reverse transcription and
integration
env- encodes the envelope glycoproteins
HIV2- lacks the vpu gene and has a vpx gene not seen in
HIV 1
Groups of HIV1
Group M- (major) responsible for most infection the world
-subtype c- most common form worldwide
Group O - outlier- cameroon, gabon, france
Group N- 1st in cameroon
Transmission: homo-heterosexual contact (most
common), bld. infected moter, perinatal, breast milk
male to female infection- more efficient mode
Genital ulcerations linked; treponema, hemophilus
ducreyi, herpes simpex
Nonulcerative STD: Chlamydia, Neisseria and
Trichomonas
Best documented factor that is assoc. higher rate of
transmission: + high level of maternal viremia
Not with exposure w/ tears, sweat and urine
HALLMARK Of Disease; profound immunodeficiency
resulting form progressive quanti and quali def of T
helper/inducer cells
CD4 molecule- primary receptor of HIV
Dissemination of virus to lymphoid organ- major factor int
he establishement of a chronic and persistent infection
Dendritic cells- important role in the intitiation of the
disease
Infection: CHRONIC AND PERSISTENT
-able to evade elimination and conrol by the
immune system; latency present
Level of CD4 + T cell- a good predictor of the pattern of th
eclinical course and devt of advanced disease
Clinical latency- asymptomatic but w/ progressive decline
w/ CD4
10 years- median time from primary HIV to AIDS
Long term non-progressors- long term survisors-
remained alive greater than 15 to 20 years after initial
infection
B5701- plays a direct role in restriction of virus
replicataon
LYMPHOID tissues- major anatomic sites for the
establishment and propagation of HIV infection
M. tuberculosis- common opportunistic infection in HIV
infected individuals, screen PPD
CD28- major co-stimulatory molecule for the normal
activation of T cells
Syncitia formation- fusion of cell membrane of an infected
cell within the cell membrane of variable numbers of
uninfected CD4
Gp 120- assoc. w/ a number of immuno pathogenic
processes incld. anergy, apoptosis and abn cell trafficking
Mx of failure of CD4
1) destruction of lymphoid precursors cells
2) gradual dysruption of the lymphoid tissue
microenvironment
NK cells- provide immunosurveillance against virus
infected cells , tumor cellsa nd alalogenic cells
Main cell types infected in the Brain: a)Perivascular
macrophages
b) microglial cells
KAPOSI'S Sarcoma-
1) Classic form- old men jewish , mediterranean and
eastern europe
2) Equatoril- african - all ages
3) organ transplant assoc
4) assoc w/ HIV 1 infxn
- angioproliferative disease , xss prolif of spindle cell,
vascular in origin and have features common w/
endothelial and smooth muscle cells
12 weeks( w/in)- antibodies to HIV appears; gag
protein,p24 and p17, gag precursor p55
V3 region- major site for the devt of mutations that lead to
variant HIV that are not well recognized by the immune
system
DX: p24 antigen capture assay; nucleic acid amplification
ELISA- standard screening test for HIV infection >99.5 %
sensitive
False + EIA- ab to class II ag, Autoab, hepatic disease,
recent influenza vaccine, acute viral infections
WESTERN BLOT- most commonly used confirmatory test
(-) WB- no bands
(+) conclusive- 2 out of 3- p24, gp41 nad gp
120/160
False (+)- absence of p31
EIA- appropriate test in px in whom HIV is suspected
HIV RNA- an essential component in monitoring of
patients w/ HIV
ACUTE HIV SYNDROME
-3 to 6 weeks after primary infection
-fever, skin rash, pharyngitis, and myalgia
ASYMPTOMATIC STAGE (LATENCY)
- median time 10 years for untreated px
SYMPTOMATIC
-severe- CD4 < 200/ul
Acute bronchitis and sinusitis- prevalent during ll stages
of HIV
Sinusitis- fever, nasal congestion and headache
MAxillary sinuses- Most commonly involve:by
encapsualted org
Pneumonia- most common manifestation of pulmonary
disease
Pneumococcal infxn- earliest serious infection to occur in
HIV
P.carinii pneumonia- once the hallmark of AIDS, decline
now
-cm: fever, cough non productive, retrosternal
pauin worse on inspiration , sharp and burning; indolent
course,xry -normal to bilateral interstitial infiltrtes
Pentamiidne tx of PCP- show upper lobe cavitary
disease like Tb
tX: TMP/SX- sta-ndard tx
Intravenous pentamidine- tx of choice for severe disease
-when given rapidly may produce hypotension
due to Cv collapse
CIProfloxacin- recommended for enteric pathogens
diarrhea- Cryptosporidia, Microsporidia, Isospora belli
Nitazoxanide- tx: cryptosporidia
Albendazole- tx: microsporidia
TMP-SMX- Isospora infxn
CMV colitis: fanciclovir/ foscarnet
Condyloma lata- most common presentation of syphilis in
HIV
Lactic acidosis- most commonly seen w/ NRTI and can
be fatal
Anemia- most common hematologic abn in HIV
C. neoformans- leading infectious cause of meningitis w/
AIDS (Amphotericin B)
HIV encephalopathy- initial AIDS-defining illnes in 3% of
px w/ HIV
Phenytoin-tx for seizures
Brain biopsy: definitive diagnostic procedure for
Toxoplasmosis
-tx: Sulfadiazine and pyrimethamine w/
leucovorin
JC Virus- progressive multifocalleukoencephalopathy
Distal sensory polyneuropathy- most common sensory
neuropathy
Cotton wool spots- most common fundoscopic exam
findings in HIV
CMV retinitis- on e of the most devastatng consequences
of HIV infection
HAART- cornerstone of management of px w/ HIV
RTI- block the HIV replication cycle at the pt of RNA dep
DNA synthesisn reverse transcription phase
NNRTI-selective for HIV1 reverse transcriptase
Side effects: mitochondrial damage: hepatic steatosis,
lactic acidosis, polyneuropathy and pancreatitis,
lipodystrophy syndrome
Regimen: 2 Nucleoside analogues+1 NRTI or 2
Nucleoside analogue + 1 protein inhibitor