Awel Abdulkerim

Assistant professor of Medicine

Department of of Internal Medicine, Health and
Medical Sceince Faculty, MWU
JAN.. 16th 2014
OUT LINE
 INTRODUCTION
 EPIDEMOLOGY

 Etiologic Agent

 Natural History of HIV Infection

 WHO Staging of HIV/AIDS

 Diagnosis of HIV Infection

 General Principles of Management

 SUMERY
HIV
Human Immunodeficiency Virus

H = Infects only Human beings

I = Immunodeficiency virus weakens the immune system
and increases the risk of infection
V = Virus that attacks the body

3
AIDS
Acquired Immune Deficiency Syndrome
A = Acquired, not inherited
I = Weakens the Immune system
•D = Creates a Deficiency of CD4+ cells in the immune system
S = Syndrome, or a group of illnesses taking place at the same time
•When the immune system becomes
weakened by HIV, the illness progresses to
AIDS
•Some blood tests, symptoms or certain
infections indicate progression of HIV to
AIDS
INTRODUCTION
 AIDS was first recognized in the US in the
summer of 1981, when the U.S Centers for
Disease Control and Prevention (CDC)
reported the unexplained occurrence of
Pneumocystis jiroveci (formerly P. carinii)
pneumonia in five previously healthy
homosexual men in Los Angeles and of
Kaposi's sarcoma (KS) with or without P.
jiroveci pneumonia in 26 previously healthy
homosexual men in New York and Los
Angeles.
INTRODUCTION

In 1983, was isolated from a patient

with lymphadenopathy,
By 1984 it was demonstrated clearly
to be the causative agent of AIDS.
In 1985, a sensitive enzyme-linked
immunosorbent assay (ELISA) was
developed
EPIDEMOLOGY

 General statistics 
  As of December 2010, 33 million people
were estimated to be living with
HIV/AIDS, and more than 35 million had
died since the beginning of the epidemic .
 Of the 33 million, 22.5 million were living
in sub-Saharan Africa alone, where the
adult prevalence rate is 5.0 percent; the
prevalence in sub-Saharan Africa appears
to have stabilized mainly due to a slowing
in the incidence and increasing number of
infected people accessing treatment
SUB-SAHARAN AFRICA

12/25/22
 Sub-Saharan Africa has been devastated by the
HIV/AIDS epidemic.
 While only 10% of the world's population lives
in sub-Saharan Africa, an estimated 70% of all
HIV infected adults and children are found
there .
 Heterosexual sexual transmission is
predominant and sub-Saharan Africa is the only
region where more women than men are infected
 ETHIOPIA HIV AND AIDS
PREVALENCE
 EWCARDC Regional Advocacy and
Communications Manager the
prevalence rate of HIV and AIDS in
Ethiopia is 1.4 per cent where as in
Kenya and Uganda it is 6.3 per cent.
 But still people have to reached messages
on safe sexual practices, access to
condoms and behaviour, he said.

, 13 June 2013 07:35

HIV/AIDS ESTIMATES AND PROJECTIONS IN
ETHIOPIA, 2011-2016
HIV/AIDS ESTIMATES AND
PROJECTIONS IN ETHIOPIA, 2011-2016
ETIOLOGIC AGENT

 HIV is the etiologic agent of AIDS; it belongs to the family

of human retroviruses (Retroviridae) and the subfamily of
lentiviruses .
 Most common cause of HIV disease throughout the world,
and certainly in the United States, is HIV-1, which
comprises several subtypes with different geographic
distributions
 Currently defined groups of HIV-1 (M, N, O, P) and the
HIV-2 groups A through G each are likely derived from a
separate transfer to humans from a nonhuman primate
reservoir.
 HIV-2 was first identified in 1986 in West African patients
and was originally confined to West Africa.
CLASSIFICATION OF HIV
 HIV class: Lentivirus
 Retrovirus: single stranded RNA transcribed to
double stranded DNA by reverse transcriptase
 Integrates into host genome
 High potential for genetic diversity
 Can lie dormant within a cell for many years,
especially in resting (memory) CD4+ T4 lymphocytes
 HIV type (distinguished genetically)
 HIV-1 -> worldwide pandemic (current ~ 40 M
people)
 HIV-2 -> isolated in West Africa; causes AIDS much
more slowly than HIV-1 but otherwise clinically
similar
CLASSIFICATION OF HIV-1
 HIV-1 groups
M (major): cause of current worldwide epidemic
 O (outlier) and N (Cameroon): rare HIV-1 groups
that arose separately
 HIV-1 M subgroups (clades)
 >10 identified (named with letters A to K)
 Descended from common HIV ancestor
 One clade tends to dominate in a geographic
region
 Clades differ from each other genetically
 Different clades have different clinical and
biologic behavior
ORIGIN AND DISTRIBUTION OF HIV-1
CLADES
 HIV-1 rapidly evolves by two mechanisms:
 Mutation: changes in single nucleosides of the RNA
 Recombination: combinations of RNA sequences from two
distinct HIV strains
 Several common clades (e.g., A/G ad A/E) are recombinants
 Geographic distribution of HIV group M clades
 A in Central Africa
 B in North American, Australia, and Europe
 C in Southern and Eastern Africa (Ethiopia)
 HIV
HIVReceptors
Receptors
HIV AND CELLULAR RECEPTORS

Copyright © 1996 Massachusetts Medical Society. All rights reserved.

HIV EVASION METHODS
 Makes 10 billion copies/day -> rapid mutation of HIV
antigens
 Integrates into host DNA
 Depletes CD4 lymphocytes
 Down-regulation of MHC-I process
 Impairs Th1 response of CD4 helper T lymphocyte
 Infects cells in regions of the body where antibodies
penetrate poorly, e.g., the central nervous system
NATURAL HISTORY OF
HIV INFECTION
STAGES OF HIV-1 INFECTION 
 HIV-1 infection is divided into the following stages:
 Viral transmission
 Primary HIV infection
 Seroconversion
 Clinical latent period
 Early symptomatic HIV infection
 AIDS
 Advanced HIV
VIRAL TRANSMISSION
HIV infection is usually acquired through
 Sexual intercourse,

 Exposure to contaminated blood, or

 Perinatal transmission. (23–30% before birth, 50–65%

during birth, and 12–20% via breast-feeding.)
 The mode of acquiring HIV infection was
undetermined in 4 % of the cases originally
reported to the CDC.
 In resource-limited areas, vaginal sex is responsible for
70 to 80 percent of AIDS cases and perinatal transmission
and injection drug use (IDU) for 5 to 10 percent each
RISK FACTORS
Risk factors for HIV transmission include :-
 Viral load,
 Lack of circumcision,
 Sexual risk,
 Presence of ulcerative STD
 Nitrate inhalant use, and
 Host and genetic factors
PRIMARY HIV INFECTION
 The period immediately after infection
characterized by high level of viremia (>1
million) for a duration of a few weeks
 Associated with a transient fall in CD4
 Nearly half of patients experience some
mononucleosis-like symptoms (fever, rash,
swollen lymph glands)
 Primary infection resolves as body mounts
HIV-specific adaptive immune response
 Cell-mediated response (CTL) followed by
humoral
 Patient enters “clinical latency”
PRIMARY HIV INFECTION
Itis estimated that 50–70% of
individuals with HIV infection
experience an acute clinical syndrome
3–6 weeks after primary infection.
Varying degrees of clinical severity
have been reported, and although it
has been suggested that symptomatic
seroconversion leading to the seeking
of medical attention indicates an
increased risk for an accelerated
course of disease
SEROCONVERSION
   Most patients seroconvert to positive HIV serology
within 4 to 10 weeks after exposure using newer
diagnostic tests, and ≥95 percent seroconvert within six
months.
 A small proportion of seroconverters demonstrate
significant immune responses and virologic control early
in infection.
 WINDOW PERIOD: UNTREATED
CLINICAL COURSE
Acute HIV syndrome
Primary antibody
Asymptomatic
HIV
infection viremia

--------------------------------------------PCR
P24
ELISA

a b Time from a to b is the window period

0 2 3 4 years
Weeks since infection Source: S Conway and J.G Bartlett, 2003

Window Period = Time between infection and detectable HIV antibodies

CLINICAL LATENT PERIOD
 Time period b/n seroconversion &onset of
HIV/AIDS-related illness
 Duration variable: < 1 year to > 15 years
 Most people remain healthy (asymptomatic) for
about three years
 Duration may depend on socio-economic factors
 The CD4 count is above 500 cells/ml
 Average rate of CD4+ T cell decline is 50/L per year.
 When the CD4+ T cell count falls to <200/L, the
resulting state of immunodeficiency is severe
enough to…
CLINICAL LATENT PERIOD
 "Persistent generalized
lymphadenopathy" (PGL)
is defined as enlarged
lymph nodes involving at
least two noncontiguous
sites other than inguinal
nodes.
EARLY SYMPTOMATIC HIV INFECTION 

The stage of early

symptomatic HIV infection is
also called "Class B"
according to the CDC 1993
classification system and was
formerly called "AIDS-related
complex".
EARLY SYMPTOMATIC HIV INFECTION 
Time period between onset of
illness & diagnosis of AIDS
Duration is variable: average
about 5 years
Illnesses initially mild, with
gradual increase in frequency and
severity
CD4 count is between 500 & 200
cells/ml
AIDS
 Final phase of HIV/AIDS

 Duration:
without antiretroviral drugs, less than 2 years
with antiretrovirals, potentially many years

 CD4 count is below 200 cells/ml

 Viral loads are high & the person is very infectious

 HIV test may become negative

ADVANCED HIV INFECTION 
 Patients with advanced HIV
infection have a CD4 cell count
below 50/mm3.
Their median survival is 12 to 18
months in the absence of
antiretroviral therapy .
Virtually all patients who die of
HIV-related complications have
CD4 cell counts in this range.
WHO STAGING OF HIV/AIDS
Tool used to guide management of
HIV patient in resource limited
settings with limited laboratory access
Clinically based; CD4 count not
required
Simple, flexible and widely used
Utilizes 5 clinical stages based on the
degree of immunocompromise and
prognosis
Primary HIV Infection, I,II, III, IV
WHO STAGING OF HIV/AIDS
 Performed at each clinical visit
 Diagnosis

 Entryto clinical care (pre-ART)

 Follow-up

 Stageassessment can be adjusted upwards

or downwards over time according to
response to ART and/or clinical
progression
WHO STAGING OF HIV/AIDS

Primary HIV Infection

Stage I - asymptomatic
Stage II - mild disease
Stage III - moderate disease
Stage IV - advanced
immunocompromise
HIV wasting syndrome: weight loss of >10% of body weight, plus
either unexplained chronic diarrhoea (>1 month) or chronic
weakness and unexplained prolongedfever (>1 month).
ESTABLISHING THE DIAGNOSIS
The diagnosis of acute HIV infection is infrequently made in clinical
practice
 The symptoms — especially in mild cases —
are nonspecific and resolve spontaneously
without treatment .
 Clinicians may be uncomfortable asking
questions about
 Primary care physicians may not be aware of
high-risk behavior
 Patients may not perceive themselves to be at
risk
PROPOSED APPROACH
For the patient who presents with an ill-defined
febrile illness, heterophile-negative
mononucleosis-like syndrome, and/or aseptic
meningitis:
 Question all patients about HIV risk
behaviors
 Perform a thorough physical examination
with particular attention to …
 Perform a HIV antibody test 2 purpose
 Obtain an HIV viral load test.
DIAGNOSIS OF HIV INFECTION

 Serological methods for detection of antibody

 Rapid tests
 ELISA
 Western blot
 Antigen detection methods
 P24 antigen capture test
 Polymerase Chain Reaction (also known as PCR or viral load)
DIAGNOSIS OF HIV ……

 CDC has recommended that screening for HIV

infection be performed as a matter of routine
health care.
 Diagnosis of HIV infection depends on the
demonstration of antibodies to HIV and/or the
direct detection of HIV or one of its
components.
 Antibodies to HIV generally appear in the
circulation 3–12 weeks following infection.
HIV SEROLOGICAL DIAGNOSIS
Tests are based on a reaction
between HIV antigens and
antibodies in the patient’s serum
Tests use viral antigen extracts as a
testing material
Both a screening test and a
confirmatory test should be used for
diagnosis
RAPID TEST

 Use two consecutive kits

 Initial test kit is very sensitive
 Repeat test is very specific
 Visual tests that do not require the ELISA Reader
 Technically simpler to perform

 Most have sensitivity and specificity comparable to

ELISA
DIAGNOSIS OF HIV ……

 Standard blood screening test for HIV infection is the

ELISA, also referred to as an enzyme immunoassay
(EIA)
 EIA tests are generally scored as positive (highly
reactive), negative (nonreactive), or indeterminate
(partially reactive).
 While the EIA is an extremely sensitive test, it is not
optimal with regard to specificity.
DIAGNOSIS OF HIV ……

 Most commonly used confirmatory test is the Western

blot .
 A negative Western blot is one in which no bands are
present at molecular weights corresponding to HIV gene
products.
 In a patient with a positive or indeterminate EIA and a
negative Western blot, one can conclude with certainty
that the EIA reactivity was a false positive
LABORATORY MARKERS OF HIV INFECTION

 Viral load
 Marker of HIV replication rate
 Number of HIV RNA copies/mm3 plasma
 CD4 count
 Marker of immunologic damage
 Number of CD4 T-lymphocytes cells/mm3 plasma
 Median CD4 count in HIV negative Ethiopians is
significantly lower than that seen in Dutch controls
 Female 762 cells/mm3 (IQR 604-908)
 Male 684 cells/mm3 (IQR 588-832)
HIV RNA SET POINT PREDICTS
PROGRESSION TO AIDS
 HIV RNA viral loads after infection can be used in the
following ways:
 To assess the viral set point
 To predict the likelihood of progression to AIDS in the next 5
years
 The higher the viral set point:
 The more rapid the CD4 count fall
 The more rapid the disease progression to AIDS
CD4 T-CELL COUNT AND
PROGRESSION TO AIDS
Incontrast to VL, baseline CD4 is not a
good predictor of time to progression to
AIDS
Unless CD4<321 cells/ml
However, as the CD4 count declines over
time, patients will develop opportunistic
infections
Developin a sequence predictable according to
CD4 count
WHO Staging system
CD4 T-CELL COUNT AND PROGRESSION
TO AIDS
Close relationship between clinical
manifestations of HIV infection and
CD4+ T cell count has made
measurement of CD4+ T cell numbers a
routine part of the evaluation of HIV-
infected individuals
CD4+ T cell count is the laboratory test
generally accepted as the best indicator
of the immediate state of immunologic
competence
GENERAL PRINCIPLES OF PATIENT
MANAGEMENT

 Discovery of a diagnosis of HIV infection is a

devastating event.
 Thus, physicians should be sensitive to this fact
and, where possible, execute some degree of
pretest counseling to at least partially prepare
the patient should the results demonstrate the
presence of HIV infection.
 Following a diagnosis of HIV infection, the
health care provider should be prepared to
immediately activate support systems for the
newly diagnosed patient
GENERAL PRINCIPLES….
Following a diagnosis of HIV
infection, there are several
examinations and laboratory studies
that should be performed to help
determine the extent of disease and
provide baseline standards for future
reference
KEY POINTS
 HIV is a retrovirus, capable of integrating into host
genome and establishing chronic infection
 HIV can be classified into subgroups (clades) which
have characteristic geographic distribution
 The important steps in the lifecycle of HIV include cell
entry, reverse transcription, integration, and
maturation/assembly
 Cell-mediated immunity is critical for containment of
HIV infection and other intracellular infections
 HIV evades host immunity by a variety of mechanisms
KEY POINTS (2)
 HIV activates the immune system to increase its own
replication
 CD4 count declines by both direct and indirect
mechanisms
 HIV RNA set point predicts rate of progression to AIDS

 CD4 count decline is associated with a predictable

sequence of opportunistic infections
REFERANCE