Transcript Slide 1

BY
DR MAHESH MATHUR,MD,DCP
DERMATOLOGIST
CMS
WHY
SHOULD WE
KNOW ABOUT THIS
DISEASE ?
 In
July 1981 – Birth Year of HIV/AIDS
 -Lawrence Altman in the New York times
 Dec.1982 Epidemic in MSM
 In 1984 –The Agent- retrovirus-HTLV III
 Renamed in 1986 HIV & serological tests
 In 1987 –Zidovudine
 Since 1996- HAART –Dramatic decrease in
Mortality
 41
million people are infected with HIV
world wide (UNAIDS)
 >70% Reside in Sub- Saharan Africa;
 App. 16000 New infection occurs Daily,
Majority Young adults.
 HIV is Leading single cause of Death in
young.
 500 Young adults & 1000 Children dieing
every day
Millions
Estimated number people living with
HIV
in Asia, 1990–2007
7
6
5
4
3
2
1
0
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
20062007
Year
This bar indicates the range
HIV-1 and the less common HIV-2 belong to the
lentivirus group of virus of the family retroviruse.
 HIV-1 contains a single-stranded RNA genome -9
genes that encode 15 different proteins.
 The major viral proteins are
 structural proteins (Gag, Pol, and Env),
 Regulatory proteins (Tat and Rev),
 Accessory proteins (Vpu, Vpr, Vif, and Nef).
 Three major classes of HIV-1
 M (main), 90%
 N (new), and
 O (outlier).
-gp120
-gp 41
-P24
Three components of the host-virus interaction.
 The virus itself - Viral strains lacking nef
sequences do not produce AIDS in their
hosts.(Australian cohort)
 Innate host factors are important in containing
infection. CCR5,CXCR4 the "second receptor" on
CD4 T cells
 The humoral and cellular arms of immune
system . Humoral responses -detectable one to
six months following infection.
 The viremia of acute infection is controlled by
cytotoxic T lymphocytes

 Cellular

immunity
CD4 helper T cells.
 The
characteristic quantitative &
qualitative depletion of CD4+ T
lymphocytes in HIV,
 Cellular destruction,
 Diminished cellular production,
 Cellular sequestration in lymphoid organs
 CD8 T lymphocytes (CTLs)- kill HIVinfected cells - immune mechanism
regulating HIV replication

SEXUAL CONTACT–53%

PERINATAL TRANSISSION –15 to 40 %



HOMO & HETERO SEXUAL CONTACT
TRANS PLACENTAL 70% of infection
DURING DELIVERY THROUGH INFECTED BIRTH CANAL 10 to 15 %
AS A RESULT OF INGESTION OF BREAST MILK CARRYING VIRUS 15%

TRANSFUSION OF BLOOD,BLOOD PRODUCTS &
ORGEN DONATION

CONTAMINATED NEEDLES


HEALTHCARE WORKERS HAVE A RISK OF APP. 0.3% FOLLOWING
A SINGLE NEEDLE-STICK INJURY WITH KNOWN HIV INFECTED
BLOOD
ACCIDENTAL INOCULATION ~0.09%
 CLINICAL
CATEGORIES
A – ADULT/ADOLESENT >13 YEARS WITH
DOCUMENTED HIV INFECTION & CONDITIONS
LISTED IN B&C NOT PRESENT
 B – CONDITIONS ATTRIBUTED TO HIV INFECTION
ORINDICATIVE OF DEFECT IN CMI AND PHYSICINE
CONSIDERING HIV INFECTION IN MANAGEMENT OF
DISEASES
 C- AIDS DEFINING CONDITIONS

PGL/ACUTE
SEROCON VERSION
HIV RELATED
CONDITION
AIDS
CASE
DEFINITION
A1
B1
C1
200-499
A2
B2
C2
<200
A3
B3
C3
ABSOLUTE
CD 4
COUNT
>500/mm3
 He
or she has a CD4+ cell count <200
cells/µL, or
 His or her CD4+ cells account for <14% of all
lymphocytes, or
 That person has been diagnosed with one or
more of the AIDS-defining illnesses listed
below.
MUCOCUTANEOUS LESIONS

Cutaneous infection associated with HIV/AIDS

Viral- HSV, VzV, Molluscum Contagiosum

Bacterial – Staphylococcus, Bacillary Angiomatosis,Mycobacteria

Fungal – Candidia,Dermatophytosis Penicillium

Parasitic infection - Scabies

Inflammatory Non infectious Dermatosis

Eosinophilic Folliculitis
Seborrheic Dermatitis
Pruritus
psoriasis

Adverse Cutaneous Drug eruptions



 HIV
& Skin Cancers
-Screen blood
-Diagnose infection,
-Monitor disease progression in individuals
infected by HIV.
1) Detect antibody,
2) Identify antigen,
3) Detect or monitor viral nucleic acids, and
4) Estimate of CD 4 +T-lymphocyte
- ELISA TEST FOR HIV-1 & 2 (gp120,41)
>99.5% SENSITVITY
FALSE POSITIVE OCCURS IN
HEPATIC DISEASE
ACUTE VIRAL INFECTIN
RECENT VIRAL VACCINATION
AUTOANTBODIES
The p24 antigen assay
The viral (core) p24 protein in blood, Detectable earlier than HIV antibody during
acute infection.
-Highly specific with high levels of viremia during which the individual is highly
infectious. PCR - 99.9%.
Testing is of value in:
-detecting early HIV infection,
-screening blood,
-diagnosing infection in the newborn,
-monitoring antiviral therapy.




-
VIRAL RNA TEST
RT-PCR
bDNA
NASBA
Where
it has succeeded,
Highly
Active Antiretroviral Therapy
(HAART)has altered the nature of
HIV disease,
Transforming
an almost uniformly
fatal illness into a chronic but
apparently stable tratable
condition.

There are currently 5 major classes of antiretroviral drugs in
general use:

Nucleoside analogue reverse transcriptase inhibitors (NRTIs),

Nonnucleoside reverse transcriptase inhibitors (NNRTIs),

Protease inhibitors (PIs),

Fusion inhibitors.

Integrase Inhibitors
 NRTIs
-Inhibit the synthesis of DNA by
reverse transcriptase, enzyme that copies
viral RNA into DNA in the newly infected
cell.
 Reverse transcriptase fails to distinguish the
phosphorylated NRTIs from their natural
counterparts & use the drugs in the
synthesis of viral DNA.
 When an NRTI is incorporated into a strand
of DNA being synthesized, the addition of
further nucleotides is prevented, and a fulllength copy of the viral DNA is not produced.

ZIDOVUDIN,DIDANSINE,LAMIVUDIN ZALCITABIN
 NNRTIs
also inhibit the synthesis of viral
DNA, but rather than acting as false
nucleotides,
 the NNRTIs bind to reverse transcriptase
in a way that inhibits the enzyme's
activity.
 DELAVIRDINE,EFAVIRENZ,NEVIRAPIN
PIs
bind to the active site of the
viral protease enzyme, preventing
the processing of viral proteins into
functional forms. Viral particles are
still produced when the protease is
inhibited, but these particles are
ineffective at infecting new cells.
INDINAVIR,RITONAVIRNELFINAVIR
 Fusion
inhibitors prevent HIV from entering
target cells.
 Drugs of this class bind to the HIV envelope
protein gp41, which is involved in viral entry.
 By blocking the interactions between regions
of the gp41 molecule, fusion inhibitors
interfere with the conformational change
(folding) of the envelope molecule required
for fusion with the target cell membrane.
 ENFUVITIDE
SYMPTOMATIC
HIV
INFECTION
ANY CD4
COUNT/VIRAL
LOAD
TREAT
ESTABLISHED
AIDS
CD4 <200
TREAT
ASYMTOMATIC
INFECTION
CD4 –
201TO350
>350
(2NRTIS+NNRTS OR
2NRTIS+PI OR
3NRTIS)
ANY VIRAL LOAD
CONSIDER
TREATMENT ON VIRAL
LOAD,CD4 DECLINING
CLINICAL CONDITION
DEFER TREATMENT







Nucleoside/Nucleotide Analogues
HYPERSNSITIVITY REACTION
SKIN RASHES & SKIN PIGMENTATION
MITOCHONDRIAL DYSFUNCTION & LACTIC ACIDOSIS
MEGALOBLASTIC ANEMIA & MYELOSUPPRESSION
POLYNEUROPATHY WITH ZALCITABIN
NAIL PIGMENTATION WITH ZUDOVUDIN

Nonnucleoside Reverse Transcriptase Inhibitors

SKIN RASHES, SJ SYNDROME

HEPATOTOXICITY

CONTRAINDICATED IN PREGNANCY

PROTEASE INHIBITORS

ABNORMAL LIVER FUNCTION

BODY FAT REDISTRIBUTION

ABNORMAL PLASMA LIPIDS

HYPERGLYCEMIA & PANCREATITIS WITH RITONAVIR & SQUINAVIR

NEPHROLITHISIS WITH INDINAVIR
The protection against exposure to HIV.
 Antiretroviral therapy cannot replace behaviours
that help avoid HIV exposure
 sexual abstinence,
 sex only in a mutually monogamous relationship
with a noninfected partner,
 consistent and correct condom use,
 abstinence from injection-drug use,
 consistent use of sterile equipment by those
unable to cease injection-drug use).
 Medical treatment after sexual, injection-drug-use, or other nonoccupational HIV exposure is
less effective than preventing HIV infection by
avoiding exposure


Non occupational exposure
Any direct mucosal, percutaneous, or
intravenous contact with potentially infectious
body fluids that occurs outside perinatal or
occupational situations e.g., health-care,
sanitation, public safety, or laboratory
employment.
 Potentially infectious body fluids are blood,
semen, vaginal secretions, rectal secretions,
breast milk or other body fluid that is
contaminated with visible blood
 Antiretroviral therapy initiated as soon as
possible within 48--72 hours of sexual, injectiondrug--use, and other substantial nonoccupational
HIV exposure

Recommendations for the prompt initiation of
nPEP with HAART
 when persons seek care within 72 hours after
exposure,
 The source is known to be HIV infected, and the
exposure event presents a substantial risk for
transmission.
 When the HIV status of the source is not known
and the patient seeks care within 72 hours after
exposure,
 PEP in not recommended for Kissing & other
sexual contact without semen/blood mucosal
contact
 The diminished potential benefit of nPEP
outweighs the potential risk for adverse events
from antiretroviral medications.

 Health
workers -Doctors, Dental
surgeons,Nurses,lab worker etc.
 Percutaneous nedlestick, deep injury,mucosal
contact or dameged skin with blood/fluids
with high viral load
 Contact of mucosa with other fluids with
high viral load
 Transmission is 0.3% before ART
 HAART for 4 weeks is recommendade
 Follow up is essential
 EDUCATION
 COUNSELING
 BEHAVIOR
 SAFER
MODIFICATION –
SEX
 MONOGAMOUS
BE
GOOD BOYS & GIRLS