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‫ُ‬

‫إل َِقلي ً‬
‫ل“‬ ‫العلم ِ َ‬
‫ِ‬ ‫ِ‬ ‫من‬
‫َ‬ ‫ِ‬
‫ُ‬
‫أوتيتم‬
‫ِ‬ ‫َ‬
‫”و َمآ‬
‫صدق ال العظيم‬
AIDS and the
skin

Prof. OSSAMA
HUSSEIN ROSHDY
AIDS and the skin

INTRODUCTION

AIDS (acquired immunodeficiency syndrome)


was first reported in the United States in 1981

AIDS is caused by HIV (human


immunodeficiency virus)
AIDS and the skin

- The initial description of the


human immunodeficiency virus
type I (HIV-1) was in 1983, and
then, HIV-2 in 1986

- Both HIV-1 & HIV-2 replicate in


CD4+ T lymphocyte
AIDS and the skin

These two viruses have been identified for


almost 20 years as the primary cause of the
acquired immunodeficiency syndrome (AIDS).

HIV-1 is the major cause of AIDS in the


world today, so, our discussion will
be primarily limited to HIV-1
AIDS and the skin

The structure of HIV-1


- HIV-1 is a single stranded RNA (retrovirus)
- Belongs to the family of lentiviruses

- Using electron microscopy, HIV-1 and HIV-2


resemble each other strikingly .
- They differ only in the molecular weight of
their proteins
AIDS and the skin

- HIV-1 viral particles have a diameter


of 100 nm and are surrounded by a
lipoprotein membrane.

- The viral particle contains all the


enzymatic equipments that are
necessary for replication: a reverse
transcriptase (RT), an integrase
(p32) and a protease (p11)
Mod of transmission
HIV Life
Cycle
HIV Life Cycle

5.
3.
4.
9.
2.
1. UNCOATING:
REVERSE
GENOME
VIRUS
FUSION:
7. PROTEIN
ASSEMBLY
8. BINDING:
6. PROTEIN
genes
TRANSCRIPTASE:
INTEGRATION:
AND
Viral andcell
SYNTHESIS:
SPREAD:
and
REPLICATION: enzymes
Cell
CLEAVAGE:
Virus attaches to a
Reverse
Viral
New
Cell integrase
membranes
uses
viral
uses HIV
particles
thefuse.
RNA
viralas a
Protease
cell enzyme
Transcriptase
splices
bud
DNA as viral
template
froma theDNA
for
cell
template
cuts long protein
copies
into
and
for cellular
viralon
synthesizing
move
reproducing RNA
DNA to
to the
viral
chain into individual
DNA
infect
HIV proteins.
RNAother cells.
genome.
proteins.
AIDS and the skin

NATURAL HISTORY:

 Rapid progressors:
Develop AIDS within 2-3 years
 Non progressors:
Remain free for 10-15 years
WHAT IS AIDS?
AIDS and the skin

CDC's definition
- All HIV-infected people who have
fewer than 200 CD4+ T cells per
cubic millimeter of blood (<
200X106 /L)
(Healthy adults usually have CD4+ T-cell
counts of 1,000 or more)
- AIDS indicator conditions: 26
clinical conditions that affect
people with advanced HIV disease
AIDS and the skin

CLINICAL PICTURE:

I- EARLY SYMPTOMS:
 Fever (38.5 °C >one month)
 Headache
 Tiredness
 Enlarged lymph nodes
AIDS and the skin
II- CASE DEFINITION of AIDS:
Category A:
Asymptomatic persistent generalized
lymphadenopathy

Category B (symptomatic):
- Conestitutional symptoms: fever and/or
diarrhoea > 1 month
AIDS and the skin

1- Candidosis (thrush, vulvovaginal):


☼ Frequent, persistent, or poorly
responsive to treatment
2- Cervical dysplasia
3- Cervical carcinoma
in-situ
AIDS and the skin

4- Oral hairy leukoplakia


5- Herpes zoster: two
episodes, > one
dermatome
AIDS and the skin

6- Idiopathic thrombocytopenic
purpura
7- Pelvic inflammatory disease
8- Peripheral neuropathy
AIDS and the skin

Category C (AIDS indicator conditions):


1- Candidal infections:
- oesophagus, trachea, bronchi, or
lungs
2- Cytomegalovirus: of any organ other
than liver, spleen, or lymph nodes
3- Herpes simplex infections:
* Mucocutaneous ulcers > 1 month
* Herpetic bronchitis, oesophagitis,
or pneumonitis
AIDS and the skin

4- HIV associated wasting:

* Involuntary weight loss (> 10% of


body weight)
* Chronic diarrhoea ( > 2 motions for
> 30 days)
* Chronic weakness and unexplained
fever for > 30 days
AIDS and the skin

5- Recurrent bacterial pneumonia


6- Pneumocystis carinii pneumonia
7- Mycobacterium avium, M kansasii
disseminated infections
8- Toxoplasmosis of internal organs
AIDS and the skin

9- Kaposi’s sarcoma in patient


younger than 60 years
10- Lymphoma; non-hodgkin’s, B cell type
11- Lymphoma of the brain in patients
younger than 60 years age
AIDS and the skin

COMMON DERMATOLOGIC
CONDITIONS ASSOCIATED WITH
HIV INFECTION:
1- Seborrhoeic dermatitis
2- Psoriasis
3- Pruritic Papular eruption
4- Viral diseases (H S, H Z,
Molluscum, warts)
AIDS and the skin

5-Pruritus - Xerosis – Ichthyosis


6- Folliculitis (bacterial,
eosinophilic )
7- Drug eruptions
8- Tinea, including onychomycosis
9- Scabies
10- Skin malignancy (BCC, SCC)
AIDS and the skin

DIAGNOSIS:
I- HIV antibody diagnosis:
- Detectable levels in the blood may need
1 to 3 months following infection
- The antibodies may take as long as 6
months to be produced in quantities
large enough to show up in standard
blood tests.
AIDS and the skin

A- Screening test (ELISA):


- They must be extremely sensitive
(100% sensitivity) to minimise the
chance of yielding a false-negative
result

- If the result is positive (reactive)


at least one confirmatory assay
AIDS and the skin

B- Confirmatory test (Western blot) :


- HIV proteins (corresponding bands) on the
Western blot are divided into three groups:

* The env or envelope glycoproteins (gp41,


gp120, gp160)
* The gag or nuclear proteins (p18, p24/25, p55)
* The pol or endonuclease-polymerase proteins
(p34, p40, p52, p68).
AIDS and the skin

II- Direct detection of HIV:


- They have higher cost, so should
only be undertaken if indicated

1- Virus isolation in cell cultures:


- Carries a certain risk
- Therefore requires the use of a high-
security laboratory.
AIDS and the skin

2- Assays for detection of HIV-1 p24


antigen: (ELISA)

3- The detection of viral nucleic acid


(virus genome ):
- To detect either proviral cDNA in leucocytes
(lymphocytes) or viral RNA in the cell-free
compartment (plasma or whole blood)
AIDS and the skin

*`Qualitative testing
- Tests for viral genome serves as a marker of
infection

* Quantitative testing

- Used as a prognostic marker


- And to estimate infectiousness
- To monitor therapy
HIV Vaccination
Mechanism of vaccine action:

1- Neutralizing antibody against HIV

2- Cytotoxic T cell responses in a vast


majority of recipients

3- strong mucosal (local)


immune responses.
 Types of Experimental HIV Vaccines:

1- Peptide vaccine:
- Made of tiny pieces of proteins from the
HIV virus.

2- Recombinant (subunit) protein vaccine:


- Bigger pieces of proteins (gp120, gp140,
or gp160 ).
- produced by genetic engineering.
3- Live vector vaccine:

- HIV genes are inserted into


another vector (non-HIV viruses)
- The genes  proteins that are
normally found on the surface of
the HIV virus  serum neutralizing
antibodies
4- DNA vaccine:
- HIV genes inserted into pieces of DNA (plasmids)

5- Virus-like particle vaccine (pseudovirion vaccine):

- A non-infectious HIV look-alike virus


- It has one or more, but not all, HIV proteins.
6-Vaccine combination "prime-
boost strategy" :

- Using any two vaccines, one after


another  stronger immune
response.
- Most researches focused on
gp120 rather than gp41/gp160

- It induced neutralizing
antibodies in nearly 100%
recipients
 Merck developed experimental
vaccine (V520)
 It prompts the body to produce
cytotoxic T –cells
 Organizers expected results in
2009
 In September 2007  vaccine
failure was declared
 Causes of vaccine failure:

- Epitopes of the viral envelope


are too variable
- Important epitopes of the gp120
are masked by glycosylation,
trimerisation
TREATMENT
1- HIV infection:
- HAART (highly active antiretroviral
therapy):

- Designed in 1996
- Multiple drugs (three or more) are used in
combination
- Can be used by people who are newly
infected with HIV as well as people with AIDS.
- HAART is not a cure for AIDS
- It has greatly improved the health of many
people with AIDS
- It reduces the amount of virus circulating in
the blood to nearly undetectable levels
- It is significantly reducing the number of
deaths from AIDS
AIDS and the skin

- FDA approved drugs


I- Reverse transcriptase (RT) inhibitors:
A- Nucleoside (RTI):
- Interrupts an early stage of the virus
making copies of itself.
- They may slow the spread of HIV in the
body
- Delay the start of opportunistic infections.
AIDS and the skin

1- Azidothymidine( AZT):
- Nausea, bone marrow suppression, and
myopathy

2- zalcitabine (ddC):
- Peripheral neuropathy

3- Dideoxyinosine (ddI ):
- Nausea, diarrhoea, pancreatitis,
gynaecomastia, and peripheral neuropathy
AIDS and the skin

4- Stavudine (d4T) :
- Gynaecomastia, and peripheral
neuropathy
5- Lamivudine (3TC):
- Nausea, bone marrow suppression,
and peripheral neuropathy
6- Abacavir (ziagen)
7- Tenofovir (viread)
8- Emtriva (emtricitabine
AIDS and the skin

B- Non-nucleoside (NNRTIs):
1- Nevirapine (Viramune) :
- Clinical and biochemical hepatitis

2- Delavirdine (Rescriptor):
- Biochemical hepatitis

3- Efavirenz (Sustiva):
- Insomnia, and nightmares
AIDS and the skin

II- Protease inhibitors:


- They interrupt the virus from making
copies of itself at a later step in its life
cycle.
1- Ritonavir (Norvir):
- Nausea, vomiting, biochemical hepatitis, and
hyperesthesia
2- Saquinavir (Invirase):
- Nausea, diarrhea
3- Indinavir (Crixivan):
- Nausea, haematuria, nephrolithiasis,
hyperbilirubinaemia
AIDS and the skin

4- Amprenavir (Agenerase):
- Nausea, diarrhea
5- Nelfinavir (Viracept):
- diarrhea
6- Lopinavir (Kaletra):
- Nausea, diarrhea
7- Atazanavir (Reyataz)
8- Fosamprenavir (Lexiva)
AIDS and the skin
III- Fusion inhibitors (Chemokines ):
Fuzeon (enfuvirtide or T-20):

- It works by interfering with HIV-1's


ability to enter into cells by blocking
the merging of the virus with the cell
membranes
- Fuzeon is designed for use in
combination with other anti-HIV
treatment
AIDS and the skin

IV- ATRIPLA:
- FDA approved in July 12, 2006
- It is the first -once- daily single tablet
regimen
- Efavirenz 600 mg/ Emtricitabine 200 mg/
Tenofovir disoproxil fumarate 300 mg
- Emtricitabine and Tenofovir are NRTIs
- Efavirenz is a non-NRTI
AIDS and the skin

- Stand-alone therapy or in combination


with other antiretroviral drugs

SIDE EFFECTS:
- Lactic acid acidosis, Hepatotoxicity
- "Flare-ups" of Hepatitis B Virus
infection
- Serious psychiatric problems
- Changes in bone density
(osteoporosis)
V- CCR5 antagonists (Maraviroc):

- Approved in august 2007


- For special type of aids called
(CCR5 -tropic HIV-1)
- It blocks the CCR5 receptors
- Used in combination with other
antiretroviral drugs
- Side effects : cough, fever, liver
dysfunction
AIDS and the skin

2- Treatment of opportunistic
infections:
 CMV (cytomegalovirus) eye infections
Foscarnet and ganciclovir

 Yeast and other fungal infections 


Fluconazole

 PCP (Pneumocystis carinii pneumonia) 


TMP/SMX (trimethoprim/sulfamethoxazole)
or pentamidine
Thank