Human

Immunodeficiency Virus
 Human Immunodeficiency
Virus
 Belongs to retrovirus family,
subfamily - lentivirus
 Retrovirus contains RNA-directed
DNA polymerase (reverse
transcriptase) – responsible for RNA to
DNA transcription, reverse of what
usually happens
 Retroviruses isolated from virtually
all vertebrate species
 Classification of retroviruses
Three subfamilies-
a. Oncovirinae – tumor viruses like Human T-cell
lymphotrophic virus (HTLV) 1 & 2, Simian
lymphotrophic virus (STLV), Avian leukemia virus,
Murine mammary tumor virus (MMTV), Avian
sarcoma virus (ASV) etc
b. Spumavirinae – viruses able to cause “foamy”
degeneration
c. Lentivirinae – agents able to cause chronic infections
with slowly progressive neurological impairment –
e.g. HIV 1 & 2, SIV (simian immunodeficiency virus),
FIV (feline immunodeficiency virus) etc
 Human retroviruses
A. Pathogenic:
a. HTLV-1 : responsible for T-cell leukemia,
myelopathy & tropical spastic paraparesis (TSP)
b. HTLV-2 : causes hairy T-cell leukemia
c. HIV-1 & HIV-2 : causative agents of
AIDS
B. Nonpathogenic:
a. Human foamy virus
b. Human placental virus
c. Human genomic virus
Important properties of lentiviruses
Nononcogenic, cytocidal retroviruses
Virion: spherical, 80-100 nm in diameter,
cylindrical core
Genome: ssRNA, linear, positive-sense, 9-10
kb, diploid; genome more complex than
oncogene
Proteins: envelope glycoprotein undergoes
antigenic variation; reverse transcriptase (RT)
enzyme contained inside virions; protease
required for production of infectious virus
Envelope: present
Replication: RT makes DNA copy from
genomic RNA; provirus DNA is template for
viral RNA. Genetic variability is common
 Properties of lentiviruses
 Maturation: particles bud from plasma membrane
 Outstanding characteristics:
* Members are nononcogenic & may be cytocidal *
Infect cells of the immune system
* Proviruses remain permanently associated with
cells
* Viral expression is restricted in some cells in vivo
* Cause slowly progressive, chronic diseases
* Replication is highly species-specific
* Group includes the causative agents of AIDS
HIV

 First case of AIDS described in 1981 in

USA
 Dr Luc Montagnier of Pasteur Institute
(France) in 1983 & Robert Gallo, the
chief of NCI of USA in 1984
independently discovered the HIV virus
now universally known as HIV-I (formerly
HTLV-3/LAV)
Global summary of the HIV and AIDS epidemic,
2007
Number of people Total 33.2 million [30.6-36.1 m]
living with HIV in Adults 30.8 million [28.2-33.6 m]
Women 15.4 million [13.9-16.6 m]
2007 Children under 15 years 2.5 million [2.2-2.6 million]

People newly Total 2.5 million [1.8-4.1 million]

infected Adults 2.1 million [1.4-3.6 million]
Children under 15 years 420,000 [350,000-540,000]
with HIV in 2007
AIDS deaths Total 2.1 million [1.8 – 4.1 million]
in 2007 Adults 1.7 million [1.6-2.1 million]
Children under 15 years 330000 [310 000 – 380 000]

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Adults and children estimated to be living with HIV, 2005

Western & Eastern Europe

Central Europe & Central Asia
North America 720 000 1.5 million
[1.0 – 2.3 million] East Asia
1.3 million [550 000 – 950 000]
[770 000 – 2.1 million] 680 000
Caribbean North Africa & Middle [420 000 – 1.1 million]
East
330 000 440 000 South & South-East
[240 000 – 420 000]
[250 000 – 720 000] Asia
Sub-Saharan Africa 7.6 million
Latin America 24.5 million [5.1 – 11.7 million]
Oceania
1.6 million [21.6 – 27.4 million]
78 000
[1.2 – 2.4 million]
[48 000 – 170 000]

Total: 38.6 (33.4 – 46.0) million

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 Over 11 000 new HIV infections a day in 2005

• More than 95% are in low and middle income

countries

• About 1500 are in children under 15 years of age

• About 10 000 are in adults aged 15 years and

older
of whom:
— almost 50% are among women
— over 40% are among young people (15-24)

06/06 e 18
 HIV/AIDS situation in
Bangladesh
 HIV/AIDS status in Bangladesh
Still low prevalent area due to:
a. People religious minded
b. STIs not highly prevalent in general population
c. Prostitution limited in urban areas where only 10-
15% people live
d. Existence of homosexuality limited
e. Injectable drug abuse not extensive
First HIV +ve case detected in 1989 in a foreigner (drug
smuggler)
First full-blown case of AIDS diagnosed in 1990 in a sea-
farer – subsequently died of persistent diarrhea
Total HIV positive case till December 2007: 1207
Developed AIDS: 365
Death – 254; death in 2007 is 14 – mostly from TB
Determinants for a severe epidemic outburst
High prevalence of HIV infection in neighboring countries
Increased population movement to & from neighboring countries
and quite considerable internal movements
Continuous international migration of labor, military personnel &
visitors
Lack of awareness of HIV infection & its possible modes of
transmission in general population
Presence of CSWs (commercial sex workers)
High prevalence of STIs especially among high-risk behavior group
Increasing trends in intravenous drug uses
Increasing number of homosexuality
Low condom usage by high-risk behavior group
Existence of promiscuity (premarital & extramarital sexual behavior)
Lack of voluntary screening of blood (about 2,00,000 units blood
transfused yearly of which 70-75% from commercial donors)
Special contextual features-
widespread poverty, unequal access of health services, subordinate
status of women, low literacy & education levels
 Modes of transmission
A. Sexual route: promiscuous sex (both
heterosxuality & homosexuality) - >75% of all cases
Heterosexuality is the main mode of
transmission in the developing countries
B. Mother to child: may be transplacental, during
delivery or due to breast feeding
Second major mode of transmission
Higher in Africa (30-40%) than in North America
or Europe (15-20%)
C. Parenteral: transfusion of infected blood or
blood products (most efficient route),
contaminated needles & syringes (IVDUs &
needle stick injury), surgical & dental
instruments, other skin piercing instruments
D. Probable other modes: through donated
organs & tissues for transplantation or through
donated semen
 HIV not transmitted by
 Casual contacts: touching,
hugging, sharing commode, hand
shaking, sharing eating & drinking
utensils, second hand clothing etc
 Blood sucking insects like

mosquitoes, bedbugs etc

 Food or water
 Transmission risk after exposure
 Blood or blood products : >90%
 Vertical route : 15-40%
(developing countries: 25-44%; industrialized nations: 13-25%)
 Injection drug use : 0.5-1%
 Genital mucous membrane : 0.2-0.5%
 Non-genital mucous
membrane spread : <0.1%
* 5-10% of new infection in children: >90% infected during
pregnancy, birth or breastfeeding
Vertical transmission: 80% close to time of delivery & 20%
in utero
* Sexual transmission: viral transmission in two ways- direct
inoculation into blood vessels by trauma & into dendritic
cells or CD4+ cells within mucosa
Virus has been isolated
from
 Blood
 Sexual fluids – semen & vaginal
secretion
 Breast milk
 Saliva
 Tears
Factors increasing the risk of HIV acquisition
• Common to all transmission categories:
high viral load
lower CD4 count
AIDS
seroconversion
• Vertical transmission:
older gestational age
prolonged rupture of membranes
vaginal versus elective caesarean delivery
chorioamnionitis
fetal trauma (e.g., scalp electrodes)
lower birth weight
no peripartum prophylaxis
first-born twin
• Breast feeding
longer duration feeding
lower parity
younger age
mastitis
 Factors --- contd
Sexual transmission:
presence of STI, especially genital ulcers
male-male versus heterosexual sex
cervical ectopy, non-circumcised
receptive versus insertive anal sex
rectal or vaginal trauma, menstruation
increased number of partners
Injection drug use transmission:
sharing equipment, intravenous use
frequency of use, cocaine use
linked commercial sex, incarceration
lower income
Occupational transmission:
deep injury, previous arterial or venous device sitting
visible blood on device
 Factors influencing the spread of HIV
• Sexual behavior:
rate of partner change (number of partners)
sexual mixing patters
size & rate of contact with core group
sexual practices (anal intercourse, intercourse during menses)
level of condom use
behavior & infection rate of partner
prevalence of injecting drug use
• Biologic variables:
level of viraemia
infectivity & virulence of HIV strains
prevalence of other STIs
lack of male circumcision
use of certain vaginal products
Factors of spread
Demographic variables:
size of population in the sexually most active
group
male to female ratio
rate & growth of urbanization
migration patterns
Economic & political factors:
response to epidemic
performance of the health care system
poverty, deprivation, lack of education
war & social disturbance
women’s status
Attitudes towards sex (role of religion)
Human Immunodeficiency Virus
Acquired Immunodeficiency syndrome first described in 1981


HIV-1 isolated in 1984, and HIV-2 in 1986



Belong to the lentivirus subfamily of the retroviridae



Enveloped RNA virus, 120 nm in diameter



HIV-2 shares 40% nucleotide homology with HIV-1



Genome consists of 9200 nucleotides (HIV-1):



gag core proteins - p15, p17 and p24



pol - p16 (protease), p31 (integrase/endonuclease)



env - gp160 (gp120:outer membrane part, gp41: transmembrane part)



Other regulatory genes i.e.. tat, rev, vif, nef, vpr and vpu

HIV particles
Together We Can Defeat the Common
Enemy
HIV
 HIV-2
 First identified in 1985, prevalent mainly in the West
Africa
 Less virulent & longer incubation period
 Spread slower & average age of infection appears to
be higher than that of HIV-1 in the same population
 STI patients & prostitutes have the highest risk of
HIV-2 infection, indicating that transmission is
mainly sexual
 Mother to child transmission & HIV-2 infection in
infants and children are unusual
 Nucleic acid of HIV-1 & HIV-2 have 40% homology,
but HIV-2 has more relatedness with SIV
 Difference between HIV 1 & HIV-2
Points HIV-1 HIV-2
Geographical World wide Mostly West
distribution Africa
Incubation period More Less
Relatedness with SIVcpz (Chimpanzee) SIVsm (Sooty
mangaby)
Envelope Gp120, gp41 Gp105,gp36
glycoprotein
Regulatory protein Vpu Vpx
Risk of transmission High Less
 Classification of HIV
 Types- two : HIV-1 & HIV-2
 Groups: s distinct groups of HIV-1: ‘M’ (Major)-
widely distributed & ‘O’ (Outlier). Recently another
group known as ‘N’ meaning new or ‘non M-non O’
Group O & N are restricted to West Africa
 Based on env gene sequences: M have 11 subtypes
(A-K); O & N have no subtypes
 HIV-2 have 5 subtypes (12-fold slower progression
to AIDS)
 Subtypes are referred to as “clades”; genetic clades
do not correspond to neutralization serotype groups
 Clade C is the fastest-spreading clade worldwide,
being present in India, Ethiopia & Southern Africa
 HIV & genetic variants
Virus group Subtypes Predominant area Association
HIV-1 M A Africa Heterosexual
Eastern Europe IDU
B Europe, North America MSM, IDU
Australia
Thailand MSM
IDU
C Southern Africa, India Heterosexual
D East & Central Africa Heterosexual
AE Thailand Heterosexual
O/N
West Africa Heterosexual
HIV-2 West Africa Heterosexual
 Origin of virus

 Possibly originated from SIV

 Sooty mangaby is the predecessor of

HIV-2
 Progenitor of HIV-1 is still not clear,

but may be chimpanzee

Disinfection & inactivation of virus
 Completely inactivated by treatment for 10 min
at room temp with any of the following
a. 10% household bleach
b. 50% ethanol
c. 35% isopropanol
d. 1% nonidet P40
e. 0.5% lysol
f. 0.5% paraformaldehyde
g. 0.3% hydrogen peroxide
h. Readily inactivated in liquids or 10%
serum by heating at 560C for 10 minute
i. Extremes of pH (1.0 & 13)
 Virus not inactivated or difficult to
inactivate
• Not inactivated by 2.5% tween-20
• Difficult to inactivate when present in
a. tissue cell culture
b. tissue specimens
c. dried proteinaceous materials
d. lyophilized blood products &
e. clotted & unclotted blood in needle and
syringes
 Major gene products of HIV that are
useful in diagnosis of infection
Gene product Description
gp160 Precursor of envelope glycoprotein
gp120 Outer envelope glycoprotein of virion, SU
p66 Reverse transcriptase & RNase H from polymerase
gene product
p55 Precursor of core proteins, polyprotein from gag gene

p51 Reverse transcriptase, RT

gp41 Trans-membrane envelope glycoprotein, TM

p32 Integrase, IN

p24 Nucleocapsid core protein of virion, CA

p17 Matrix protein of virion, MA
HIV Genome
Morphology of HIV & composition of its genome
Virus particle: from within outwards-
a. a pear shaped core of protein (p24-
major capsid protein) inside which two
separate strands of RNA each with RT &
protein ag (p7& p9- nucleocapsid protein).
Core also contains enzymes like protease
& integrase
b. Core is covered by a soccer shaped
outer shell of protein (p18)
c. A lipid bilayer outer coat (envelope)
with glycoprotein ag : gp160 (gp120-outer
membrane part & gp41- transmembrane
part)
 Viral genome
 Consists of-
a. 3 major genes – gag, pol & env
responsible for encoding structural
proteins of virion – required for a
replicating retrovirus
b. 6 regulatory genes – vif, vpr, vpu,
tat, rev & nef
c. All these 9 genes are capped by two
LTR (long terminal repeat) genes
 HIV genes & their functions
Gene type Genes Functions/encoding
A. Major gag Group antigens proteins: p24, p17/18, p9
genes
pol Polymerase (RT), protease, integrase
encoding
structural env Envelope glycoproteins: gp160, gp120,
proteins gp41
LTR Long terminal repeats: containing promoter
& enhancing sequences
B. nef Negative regulatory factor
Regulatory
rev Expression of viral structural proteins
(regulatory for virion proteins
tat Transactivator protein stimulator
vif Virion infectivity factor
vpr Weak transcriptional activator
vpu Efficient budding
Viral entry
 Viral replication
 Receptors for HIV: (2 major targets are immune system & CNS)
CD4 molecules
Galactosyl ceramide in place of CD4 in neural cells
Chemokine co-receptors for HIV-1 (second receptors that
facilitate the entry of the virus
 Chemokines are soluble factors with chemoattactrant & cytokine
properties
 CCR5: receptor for chemokines RANTES (regulation upon
activation, normal T expressed & secreted), MIP-1α (macrophage
inflammatory protein) and MPI-1β is the co-receptor for M tropic
strains (infect macrophage/monocyte & T cells) of HIV-1
 CXCR4: receptor for chemokine SDF-1 is the necessary co-
receptor for lymphocyte (T)-tropic strains of HIV-1
 Second receptor required for fusion of virus with cell membrane.
Virus binds to CD4 & then to second receptor. These interaction
cause conformational changes in viral envelope, activating gp41
fusion peptide & triggering membrane fusion
Schematic of HIV
Replication
 Sequence of events
• Replication takes place inside target cells mainly CD4+ T
lymphocytes
I. Specific union: between gp120 & CD4
gp120+CD4 → change in gp120 → exposure of gp41 → union
of chemokine co-receptor on target cells with gp120 → pores in
cell surface → viral entry
II. Entry: entry of viral RNA with enzymes into cells – viral RNA
floats in the cytoplasm for a while
III. RNA → DNA: conversion of viral RNA to dsDNA by RT
IV. Circularization: of dsDNA
V. Provirus: integration of dsDNA into host chromosome as
provirus with help of enzyme integrase
VI. Activation: of provirus that starts transcribing viral mRNA &
genomic viral RNA
VII. Translation: mRNA translates viral proteins that are sized by
proteases. Nucleocapsids are thus formed that encapsidate
molecules of genomic RNA giving rise to new progeny of HIV
VIII. Budding out: enveloped by a lipid bilayer of cell membranes
I. Union: [gp120+CD4+gp41+chemokines coreceptor] → Pores in
target cell
↓
II. Entry: viral RNA & enzymes into target cell
↓
III. RNA → DNA conversion (action by RT)
↓
IV. Circularization of ds DNA
↓
V. Provirus: integration of dsDNA in chromosomes of cell (action by
integrase)
↓
VI. Activation of provirus → transcription : viral mRNA & genomic
viral RNA
↓
VII. Translation by mRNA: mRNA translates viral proteins sized by
protease. Proteins encapsidate genomic RNA → new progeny of HIV
↓
VIII. Budding out of new generation of viruses → enveloped by lipid
bilayer of host cells
 HIV half-lives
 Activated cells that become infected with HIV produce virus
immediately and die within one to two days.
 Production of virus by short-lived, activated cells accounts for the vast
majority of virus present in the plasma.
 The time required to complete a single HIV life-cycle is approximately
1.5 days.
 Resting cells that become infected produce virus only after immune
stimulation; these cells have a half-life of at least 5-6 months.
 Some cells are infected with defective virus that cannot complete the
virus life-cycle. Such cells are very long lived, and have an estimated
half-life of approximately three to six months.
 Such long-lived cell populations present a major challenge for anti-
retroviral therapy.
 HIV Pathogenesis
 The profound immunosuppression seen in AIDS is due to the depletion of
CD4 helper lymphocytes (CMI) – predisposes to various opportunistic
infections & certain cancers.
 After mucosal exposure transported to lymph nodes via dendritic cells
(DC), CD4 cells or Langerhans cells. DC express receptors – e.g. DC-
SIGN – that facilitate capture & transport of HIV-1
 In the immediate period following exposure, HIV is present at a high level
in the blood (as detected by HIV Antigen and HIV-RNA assays).
 Free or cell-associated virus disseminated widely through blood with
seeding to sanctuary sites
 It then settles down to a certain low level (set-point) during the incubation
period. During the incubation period, there is a massive turnover of CD4
cells, whereby CD4 cells killed by HIV are replaced efficiently.
 Eventually, the immune system succumbs and AIDS develop when killed
CD4 cells can no longer be replaced (witnessed by high HIV-RNA, HIV-
antigen, and low CD4 counts).
 HIV Pathogenesis
Transfer of
virus to
regional
lymph nodes

Spread of
infection to
activated
CD4+
lymphocytes

Entry of Days
virus-infected
cells into the
bloodstream

Widespread
dissemination
Brain Spleen Gut Lymph
nodes

NEJM 339:36, 1998

 Sanctuary of HIV
 CNS
 Spleen
 Testes
 Intestinal mucosal lymphoid tissue
 Latently infected CD4 cells

* Each day >1010 virions produced; 109 CD4 cells destroyed ( daily
turnover of 30% of total viral burden & 6-7% of total)

* <0.01% CD4 cells → post-integrated latent phase – main reservoir

* Plasma half-life of virus → 1-2 hrs; 1.5 days in productively infected

CD4 cells & >12 months in latently infected cells
 Primate Model
Mucous Membrane Exposure to
HIV
• Infection of dendritic
cells within 24 hours
• Next 24-48 hours
lymph nodes infected
• Virus in blood in 5 days
• Generation time 2.5
days
• Burst size 5,000
particles per cell
• After integration, the provirus may remain locked into the
chromosome for months or years, & hence the infection
become latent
• CMV, EBV, HBV & M tuberculosis enhance replication of
HIV by activation of macrophages & T cells
• HIV carried to the brain by infected monocytes
(circulating monocyte – infection is low)
• HIV isolates from brain – exclusively M-tropic
• Neurons are not infected by HIV
• Neurologic symptoms – cytokines mediated: IL-1, TNF &
IL-6 & also NO
• Virus inoculated into blood – rapidly cleared by the
spleen & lymph nodes – replicates in the lymphoid
organs – then spills over into the blood
• HIV multiply in terminally differentiated nondividing
macrophages – dependent on vpr gene
 Implications of infection of
macrophages
Monocytes & macrophages represent a
veritable virus factory & reservoir
Provides a safe vehicle for HIV to be
transported to various parts of the body,
including nervous system
In late stages of HIV infection, when the
CD4+ T-cell number decline greatly,
macrophages may be an important site
of continued viral replication
 Mechanism of evasion of immune system

 Three main mechanisms:

a. integration of viral DNA into host cell
DNA, resulting in a persistent infection
b. a high rate of mutation of the env gene
c. the production of the tat & nef proteins
that down regulate class I MHC proteins
required for cytotoxic T cells to recognize &
kill HIV-infected cells
 Main immune response to HIV infection consists
of cytotoxic CD8-positive lymphocytes
 Why Antibody Is Ineffective
(The 2 unfoldings needed to expose
the hidden cell-binding site)

CCR5
CD4

3. CCR5 binding causes 2nd

1. HIV envelope 2. CD4 binding of envelope conformational change, exposing
nears cell causes conformational change the double-hidden binding site
 Natural history of HIV infection
Primary infection:
viral replication occurs & virus disseminated in the body (in
2-4 wks) & lymphoid organs become seeded
Period between mucosal infection & initial viraemia: 4-11 d
Viraemia detectable for about 8-12 wks
Seroconversion illness: acute mononucleosis-like (flu-like)
syndrome with fever, lymphadenopathy & rash in 50-75%
cases 3-6 wks after primary infection
Significant drop in number of circulating CD4 T cells at this
stage
Immune response after 1 wk to 3 months after infection
Plasma viraemia drops & levels of CD4 cells rebound
Immune response unable to clear infection completely & HIV
persists in lymph nodes
CDC group I is marked by:
a. Seroconversion illness b. Viraemia
c. p24 ag d. gp41 ab
e. p24 ab f. beginning decline of CD4 counts
 Clinical latency: Carrier stage (CDC
group II)
• May last for 10 yrs
• High level of ongoing viral replication – 10 billion
HIV particles are produced & destroyed each day
• Half-life of virus in plasma is about 6 hrs & viral life
cycle averages 2.6 days
• CD4 also high turnover rates: half-life about 1.6 days
• Every possible nucleotide of HIV genome probably
mutates on a daily basis
• Symptomless
Beginning of disease process –
PGL (Progressive generalized
lymphadenopathy

• Immune system loses the

battle
• With death of CD4 cell
release of numerous viruses
that attack new CD4 cells
• Patients may develop PGL
 Symptomatic HIV infection: AIDS
 Definition of AIDS: it is condition in which common
curable infectious diseases turn into incurable forms or
appear generalized neoplasms due to immune deficiency
caused by HIV infection
 Lymphopenia with marked reduction in CD4 cells
 High plasma viral load, reappearance of p24 antigen
 Viral shift from a less virulent M-tropic strains to more
virulent T-tropic strains
 M-tropic strains reach brain (neuropsychiatric
manifestations), lung (alveolar pneumonia), & lymphoid
tissues (lymphadenopathies)
 Patients develop myriads of constitutional symptoms &
become vulnerable to opportunistic infections &
neoplasms
 According to CDC 5 subgroups
 A = constitutional diseases (ARC – AIDS related
complex) – lassitude, fever (>1 month), wt loss
(>10%), diarrhea (>1 month)
 B = neurological diseases (ARC)
Dementia, peripheral neuropathy, atypical aseptic
meningitis
 C = invasive opportunistic infections (mainly
intracellular)
 D = malignancies: Kaposi’s sarcoma, lymphoma,
squamous carcinomas & Barkitt’s lymphoma
 E = others
 Encephalitis may be due to direct infection of HIV or
secondary infection by agents like HSV or cryptococcus
 AIDS defining diseases
 Oesophageal candidiasis, candidiasis of bronchi or pulmonary tree
 Cryptococcal meningitis
 Chronic cryptosporidial diarrhea
 CMV retinitis or colitis
 Chronic mucocutaneous disseminated herpes simplex
 Disseminated M avium intracellulare or M kansasii infection
 Pulmonary (CD4 <200/mm3) or extrapulmonary tuberculosis
 Pneumocytis jirovecii pneumonia
 Progressive multifocal leucoencephalopathy
 Repeated non-typhi Salmonella septicaemia
 Cerebral toxoplasmosis, extraintestinal strongyloidiasis
 Extrapulmonary coccidioidomycosis
 Invasive cervical cancer
 Extrapulmonary histoplasmosis
 Kaposi’s sarcoma
 Non-Hodgkin lymphoma
 Primary cerebral lymphoma
 HIV-associated wasting
 HIV-associated dementia
Kaposi’s Sarcoma
 Common opportunistic infections in AIDS
• Viruses: CMV, HSV, VZV, adenoviruses, JC papova virus,
HBV, EBV (Hairy cell leukoplakia)
• Bacteria: M tuberculosis, M avium intracellulare, M kansasii,
Nocardia asteroides, L monocytogenes, Salmonella species,
Streptococcus species
• Fungus: Pnemocystis jirovecii, C albicans, Cryptococcus
neoformans, Coccidioides immitis, H capsulatum,
• Protozoa: T gondii, Isospora belli, Cryptosporidium parvum,
Microsporidium
• Helminthes: S stercoralis
• Co-infection with DNA viruses can lead to enhanced
expression of HIV in cells
• Predominant opportunistic infections – intracellular pathogens
– susceptible to CMI rather than humoral immune response
 Potential role of macrophages in the
pathogenesis of AIDS
a. Act as target for HIV
b. Provide reservoir for HIV
c. Contribute to immune deficiency through
abnormal function-
defective phagocytosis
defective chemotaxis
defective antigen presentation
abnormal cytokine production
d. Contribute to T cell depletion through a cell
fusion process
 Immunological abnormalities in AIDS
A. T-helper (CD4) lymphocytes (mainly Th1)
a. Decreased in number (low CD4 count in peripheral
blood)
b. Abnormal function:
reduced responses (delayed type) to antigen or mitogen
reduced responses to IL-2
reduced production of IL-2 & IFNγ
B. B lymphocytes – abnormal functions
reduced responses to specific antigen or mitogen
polyclonal activation leading to increases in Ig

C. Monocytes/macrophages & dendritic cells

a. Defective ag presentation
b. Defective cytokine secretion (IL-1, TNF & IL-6)
c. Defective chemotaxis, phagocytosis/killing
 Destruction of CD4 cells
A. Viral replication
B. Syncytium formation via membrane
gp120 binding to cell CD4 ag
C. Cytotoxic T cells lysis of infected cells
D. Cytotoxic T cell lysis of CD4+ cells
carrying gp120 released from infected
cells
E. Natural killer cells
F. Antibody-dependent cell cytotoxicity
 Categories of HIV Testing

1. Mandatory Testing
2. Voluntary Counseling and Testing
3. Routine Testing
4. Diagnostic Testing
 Laboratory diagnosis
 Evidence of HIV infection can be detected in three
ways-
a. Virus isolation
b. Measurement of viral nucleic acid or antigen
c. Serologic determination of antiviral
antibodies

 Nonspecific tests:
Leukopenia with lymphopenia
Reversal of CD4:CD8 ratio
High ESR
Cutaneous anergy
Functional abnormalities of macrophages, B cells etc
 Virus isolation
 Can be cultured from lymphocytes & occasionally
from specimens from other sites
 Number of circulating infected cells vary with the
stage of disease – higher in AIDS
 Most sensitive virus isolation technique is to
cocultivate test sample with uninfected, mitogen-
stimulated peripheral blood mononuclear cells
 Viral growth detected by testing culture supernatant
fluids after 7-14 days for-
viral RT activity or
virus specific antigen – p24
 Culture is time consuming & laborious
 Used for diagnosis of HIV infection in babies born to
HIV infected mothers
 Detection of viral nucleic acid or antigen
► p24:
detected in plasma by ELISA soon after infection
disappear after appearance of ab
reappearance indicate poor prognosis –
development of AIDS
► Viral load:
detection of viral nucleic acid by RT-PCR,
branched chain DNA9bDNA), NASBA etc
can detect as little as 400 viral RNA copies/ml of
blood
important markers for disease progression &
valuable in monitoring effective of antiviral
therapy (two baseline tests & then every 3
months)
 Serology
 Serology is the usual method for diagnosis
 Normally takes 4-6 weeks before HIV-antibody appears following
exposure
 Antibodies to core protein p24 or envelope glycoprotein gp41,
gp120 or gp160 more commonly detected
 Divided into screening assay & confirmatory test
 Screening assay:
a. ELISA – commonly performed
b. Immunochromatographic test (ICT)
c. Membrane ELISA or spot ELISA
d. Particle agglutination test (PAT) – not used now
 HIV-1 ELISA can detects 40-90% of HIV-2 infections
 Positive test repeated with fresh sample & confirmed by Western
blot
 False-positive ELISA: individuals having immunologic
abnormalities or neoplasms or who have been multiply transfused
ELISA for HIV antibody

Microplate ELISA for HIV antibody: colored wells

indicate reactivity
Abbott Determine Rapid HIV Test
POSITIVE NEGATIVE INVALID INVALID
472U100 472U100 472U100 472U100

HIV-1/2 HIV-1/2 HIV-1/2 HIV-1/2

7A 7A 7A 7A
CONTROL

CONTROL

CONTROL

CONTROL
PATIENT

PATIENT

PATIENT

PATIENT
 Trinity Biotech Unigold
Rapid Test
POSITIVE NEGATIVE INVALID INVALID
 Confirmatory test
Western blot: commonly used – gold standard
test
Other tests are – immunofluorescence test,
radioimmunoprecipitation test
In Western blot – antibodies to HIV proteins of
specific molecular wts can be detected. HIV
proteins on nitrocellulose strips are gp160, gp41,
p65, p55, p51, p31, p24 & p18
For positive test any 2 or 3 major bands must be
present (gp160, and/or gp120, gp41 & p24)
By Lia Tek HIV III line immunoassay HIV-1 &
HIV-2 can be separated. Ag lines are gp120,
gp41, p31, p24, p17, gp106, & gp36
gp106 (gp105) & gp36 present in HIV-2
Western blot for HIV antibody

 There are different criteria for

the interpretation of HIV
Western blot results e.g. CDC,
WHO, American Red Cross.
 The most important antibodies
are those against the envelope
glycoproteins gp120, gp160,
and gp41
 p24 antibody is usually present
but may be absent in the later
stages of HIV infection
 Military HIV Screening
• Accuracy
• Privacy
• Stigmatization
• Pre- and post-test
counseling
• Follow on care for
those found positive
Laboratory markers associated with
progression of HIV infection
a. Number of CD4 lymphocytes
b. Increasing proportion of infected CD4 cells
c. Increasing titre of virus in plasma (HIV RNA copy
number)
d. p24 antigen in plasma
e. Isolation of virus in culture – rapid growth,
syncytium formation
f. Loss of antibody to p24
g. Elevated β2-microglobulin level
h. Elevated serum neopterin level
i. Elevated serum soluble IL-2 level
j. Loss of cutaneous hypersensitivity
 Prevention measures for HIV
transmission
Only way to avoid epidemic spread of HIV to
maintain a lifestyle that minimizes or eliminates
high-risk factors
Sexual:
a. public awareness campaigns for HIV
b. safe sex practices-
avoidance of premarital & extramarital sexual
intercourse
avoidance of penetrative intercourse with risk
groups
be faithful to your spouses
use of condoms
c. targeting safe sex methods at sex industry workers
d. control of STIs
e. strict adherence to religion
f. Post-exposure prophylaxis
 Prevention of HIV
 Parenteral:
a. routine screening of blood & blood products
b. needle exchange programmes for IVDUs
c. universal health care precautions
d. voluntary non-remunerated blood donation
e. toothbrushes, razors & other implements that
could be contaminated with blood should not be shared
 Perinatal:
a. routine HIV testing in antenatal clinics
b. avoidance of pregnancy in HIV positive
c. antiretroviral therapy during
pregnancy/delivery/postnatally
d. avoidance of breastfeeding
 Health education
ABC of HIV prevention

• Abstinence
• Being Faithful
• Condoms
 Beyond the ABC
1. Get tested
2. No unprotected sex without certainty of your
partner’s HIV status
3. If HIV-positive, get into care
4. If HIV-negative, protect your status
5. Undiagnosed HIV in pregnancy kills children
6. Your undiagnosed HIV could kill your partner
7. Your partner’s undiagnosed HIV could kill you
 You can not see HIV!

You can not even guess

who might have it!
 The
incidence of
Between
HIV in
75%
Commercial
and
Sex
90%
Workers in
most areas
is
A smile can be Or an
a signal of invitation
friendship
The cultural signals are different from
culture to culture!

A red rose A white rose

can mean can mean
Love Peace
or or
Revolution Death
A veil can signal Showing hair can
repression signal an invitation

Or Chastity Or pride
 The daily death toll from AIDS in the next 10 years

Will be Four WTT

like explosions
 HIV
IS
A DEADLY VIRUS!

HIV INFECTION IS
PREVENTABLE!
 There is no vaccine against HIV!

There is no known cure for AIDS!

Present treatment can postpone death,

but not prevent it!

Present treatment has unpleasant side-

effects, and makes people
totally dependant on exact time
 Antiretroviral drugs
A. Nucleoside RT inhibitors (NRTIs)
Zidovudine (ZDV) Zalcitabine (ddC)
Didanosine (ddI) Stavudine (d4T)
Lamivudine (3TC) Abacabir
Emitricitabine (FTC)
B. Non-nucleoside RT inhibitors (NNRTIs)
Nevirapine Delavirdine
Loviride Efavirenz
C. Protease inhibitors (PIs)
Indinavir Ritonavir
Nelfinavir Lopinavir
Atazanavir Fosamprenavir
Saquinavir Tipranavir
Amprenavir
D. Other: Tenofovir Entuvirtide (T-20)
 Antiretroviral drugs
• RT inhibitors prevent spread of infectious virus into
uninfected cells but do not affect replication of HIV
genome once integrated into host cells
• Protease inhibitors prevent post-translational
cleavage of polypeptides into functional viral
proteins
• No monotherapy; mild cases – 2 drugs: zidovudine
& lamivudine or lamivudine & stavudine
• More severe cases: triple drug therapy: 2 RT
inhibitors + one protease inhibitor known as
HAART (highly active antiretroviral therapy)
Post-exposure prophylaxis (PEP)
 Prophylaxis after occupational exposure to
healthcare workers
 Also used in condom breakage in HIV-
serodiscordant partners, victims of rape, relapses
in IDUs & sharps-related home exposures in
families of HIV patients
 Recommended PEP: ZDV, lamivudine & indinavir
or nelfinavir for 28 days
 First dose as soon as possible
 Protection not absolute
 Periodic serological test to see seroconversion
 Base line investigations
 CD4 count, Viral load
 HBV status
 HCV status
 Cervical smear in women
 HAV IgG ab
 Toxoplasma ab
 CMV IgG ab
 Treponema serology
 Genitourinary medicine screen
 CD4 <200 cells/mm3
Chest x-ray, HCV-RNA, cryptococcal ag, stool for ova, cysts
& parasites
 CD4 <100 cells/mm3
CMV-RNA, dilated fundoscopy, ECG, Mycobacterial culture
 Correlation between CD4 cell count &
HIV-associated diseases
 >500 cells/mm3
acute primary infection recurrent vaginal candidiasis
persistent generalized lymphadenopathy
 <500 cells/mm3
Pul tuberculosis Kaposi’s sarcoma
HIV-associated ITP Pneumococcal pneumonia
Cervical intra-epithelial neoplasia Herpes zoster
Oropharyngeal candidiasis Oral hairy leukoplakia
Lymphoid interstitial pneumonitis Extra-intestinal salmonellosis
 <200 cells/mm3
P jirovecii pneumonia Oesophageal candidiasis
Miliary/extrapulmonary tuberculosis Cryptosporidium
Mucocutaneous herpes simplex Microsporidium
Peripheral neuropathy
 <100 cells/mm3
Cerebral toxoplasmosis Cryptococcal meningitis
HIV-associated dementia Primary CNS lymphoma
Non-Hodgkin lymphoma
Progressive multifocal leucoencephalopathy
 <50 cells/mm3
CMV retinitis/gastrointestinal disease Disseminated M avium intracellulare
 Indication to start HAART
CD4 count Decision
(cells/mm3)
Seroconversion Consider
>350 Monitor 2-3 monthly

200-350 Monitor/recommended
based on symptoms &
VL

<200 Recommend
 Replication
 The first step of infection is the binding of gp120 to the
CD4 receptor of the cell, which is followed by
penetration and uncoating.
 The RNA genome is then reverse transcribed into a DNA
provirus which is integrated into the cell genome.
 This is followed by the synthesis and maturation of virus
progeny.
 HIV-1 Genotypes
 There are 3 HIV-1 genotypes; M (Main), O (Outlayer), and N (New)
 M group comprises of a large number subtypes and recombinant forms
 Subtypes - (A, A2, B, C, D, F1, F2, G, H, J and K)
 Recombinant forms - AE, AG, AB, DF, BC, CD
 O and N group subtypes not clearly defined, especially since there are
so few N group isolates.
 As yet, different HIV-1 genotypes are not associated with different
courses of disease nor response to antiviral therapy.
 However, certain subgroups may be difficult to detect by certain
commercial assays.
 Clinical Features
1. Seroconversion illness - seen in 10% of individuals a few weeks
after exposure and coincides with seroconversion. Presents with
an infectious mononucleosis like illness.
2. Incubation period - this is the period when the patient is
completely asymptomatic and may vary from a few months to a
more than 10 years. The median incubation period is 8-10 years.
3. AIDS-related complex or persistent generalized lymphadenopathy.
4. Full-blown AIDS.
 Opportunistic Infections
Protozoal Pneumocystis jirovecii (now thought to be a fungi),
toxoplasmosis, crytosporidosis

Fungal candidiasis, crytococcosis

histoplasmosis, coccidiodomycosis

Bacterial Mycobacterium avium complex, MTB

atypical mycobacterial disease
salmonella septicaemia
multiple or recurrent pyogenic bacterial infection

Viral CMV, HSV, VZV, JCV

 Opportunistic Tumours
 The most frequent opportunistic tumour, Kaposi's
sarcoma, is observed in 20% of patients with AIDS.
 KS is observed mostly in homosexuals and its relative
incidence is declining. It is now associated with a human
herpes virus 8 (HHV-8).
 Malignant lymphomas are also frequently seen in AIDS
patients.
 Other Manifestations
 It is now recognised that HIV-infected patients may
develop a number of manifestations that are not explained
by opportunistic infections or tumours.
 The most frequent neurological disorder is AIDS
encephalopathy which is seen in two thirds of cases.
 Other manifestations include characteristic skin eruptions
and persistent diarrhoea.
 Epidemiology
1. Sexual transmission - male homosexuals and constitute the largest risk
group in N. America and Western Europe. In developing countries,
heterosexual spread constitute the most important means of transmission.
2. Blood/blood products - IV drug abusers represent the second largest AIDS
patient groups in the US and Europe. Haemophiliacs were one of the first
risk groups to be identified: they were infected through contaminated factor
VIII.
3. Vertical transmission - the transmission rate from mother to the newborn
varies from around 15% in Western Europe to up to 50% in Africa.
Vertical transmission may occur transplacentally route, perinatally during
the birth process, or postnatally through breast milk.
4. In 2003, an estimated 4.8 million people (range: 4.2–6.3 million) became
newly infected with HIV. This is more than in any one year before. Today,
some 37.8 million people (range: 34.6–42.3 million) are living with HIV,
which killed 2.9 million (range: 2.6–3.3 million) in 2003, and over 20
million since the first cases of AIDS were identified in 1981.
 Laboratory Diagnosis
 Serology is the usual method for diagnosing HIV infection.
Serological tests can be divided into screening and confirmatory
assays. Screening assays should be as sensitive whereas confirmatory
assays should be as specific as possible.
 Screening assays - EIAs are the most frequently used screening
assays. The sensitivity and specificity of the presently available
commercial systems now approaches 100% but false positive and
negative reactions occur. Some assays have problems in detecting
HIV-1 subtype O.
 Confirmatory assays - Western blot is regarded as the gold standard
for serological diagnosis. However, its sensitivity is lower than
screening EIAs. Line immunoassays incorporate various HIV antigens
on nitrocellulose strips. The interpretation of results is similar to
Western blot it is more sensitive and specific.
 Other diagnostic assays
 It normally takes 4-6 weeks before HIV-antibody appears
following exposure.
 A diagnosis of HIV infection made be made earlier by the
detection of HIV antigen, pro-DNA, and RNA.
 However, there are very few circumstances when this is
justified e.g. diagnosis of HIV infection in babies born to
HIV-infected mothers.
 Prognostic tests
Once a diagnosis of HIV infection had been made, it is
important to monitor the patient at regularly for signs of
disease progression and response to antiviral chemotherapy.
HIV viral load - HIV viral load in serum may be measured by assays
which detect HIV-RNA e.g. RT-PCR, NASBA, or bDNA. HIV viral load
has now been established as having good prognostic value, and in
monitoring response to antiviral chemotherapy.

HIV Antigen tests - they were widely used as prognostic assays. It was
soon apparent that detection of HIV p24 antigen was not as good as serial
CD4 counts. The use of HIV p24 antigen assays for prognosis has now
been superseded by HIV-RNA assays.
 Anti-Retorviral Susceptibility Testing
 It is now generally accepted that anti-viral susceptibility testing should
be a routine part of the management of HIV-infected patients.
 It is reported that the outcome would be better if the results are
interpreted by an expert in this area.
 There are two types of antiviral susceptibility assays:
 Phenotypic – very difficult and expensive to carry out. Thought to give a
better idea of the actual situation in vivo.
 Genotypic – the RT and Protease genes are sequenced. This can be done
in-house and the results interpreted automatically by the HIV sequence
database in the US.
 http://resdb.lanl.gov/Resist_DB/default.htm
 Commercial systems (Trugene, ABI and others) available which relies on
their own database and interpretation by a panel of experts that meet
regularly.
 Treatment
 Zidovudine (AZT) was the first anti-viral agent shown to have
beneficial effect against HIV infection. However, after prolonged
use, AZT-resistant strains rapidly appears which limits the effect of
AZT.
 Combination therapy has now been shown to be effective,
especially for trials involving multiple agents including protease
inhibitors. (HAART - highly active anti-retroviral therapy)
 The rationale for this approach is that by combining drugs that are
synergistic, non-cross-resistant and no overlapping toxicity, it may
be possible to reduce toxicity, improve efficacy and prevent
resistance from arising.
 Anti-Retroviral Agents
 Nucleoside analogue reverse transcriptase inhibitors e.g. AZT,
ddI, lamivudine
 Non-nucleoside analogue reverse transcriptase, inhibitors e.g.
Nevirapine
 Protease Inhibitors e.g. Indinavir, Ritonavir
 Fusion inhibitors e.g. Fuzeon (IM only)
 HAART (highly active anti-retroviral therapy) regimens
normally comprise 2 nucleoside reverse transcriptase inhibitors
and a protease inhibitor. e.g. AZT, lamivudine and indinavir.
Since the use of HAART, mortality from HIV has declined
dramatically in the developed world.
 Prevention
 The risk of contracting HIV increases with the number of sexual partners. A
change in the lifestyle would obviously reduce the risk.
 The spread of HIV through blood transfusion and blood products had virtually
been eliminated since the introduction of blood donor screening in many
countries.
 AZT had been shown to be effective in preventing transmission of HIV from
the mother to the fetus. The incidence of HIV infection in the baby was
reduced by two-thirds.
 The management of health care workers exposed to HIV through inoculation
accidents is controversial. Anti-viral prophylaxis had been shown to be of
some benefit but it is uncertain what is the optimal regimen.
 Vaccines are being developed at present but progress is hampered by the high
variability of HIV. Since 1987, more than 30 HIV candidate vaccines have
been tested in approximately 60 Phase I/II trails, involving more than 10,000
healthy volunteers. A phase III trial involving a recombinant gp120 of HIV
subtype B was reported in Feb 2005 to be ineffective in preventing HIV
infection.
 Mandatory Testing

• Specific Clinical applications

- Organ and blood donation
• Pre-Employment screening
- Many militaries
• Pre-Deployment testing
- UN Peace Keeping Missions
Voluntary Counseling and Testing

• Two different, rapid, simple

whole blood tests are used
for every client
• Done on site by trained
Counselor
• Confirmed results in 15 to
20 minutes
• Tests used at present:
– Abbott Determine
– Trinity Biotech UniGold
 Routine HIV Testing
• Routine Testing – routine performance of
HIV test for service delivery, analogous to
syphilis testing, e.g. for:
- Antenatal testing
- Sexual health services
 Diagnostic HIV Testing
• Diagnostic Testing – routine performance of
HIV test for diagnostic purposes
- for symptomatic patients
- for tuberculosis patients
• Increased diagnostic testing essential for OI
prophylaxis and ARV delivery
 Diagnostic HIV Testing
• > 50% tuberculosis patients are HIV+
• >50 % hospital patients are HIV+
• HIV status has implications for medical
management, prognosis, and prevention
• Delay in HIV diagnosis has adverse
consequences on patient management
• Routine diagnostic testing for medical and
tuberculosis patients should be considered
 Human
immunodeficiency virus
Global trend of HIV
HIV/AIDS around world
 Global estimates for adults and children, 2005

• People living with HIV 38.6 million [33.4 – 46.0 m]

• New HIV infections in 2005 4.1 million [3.4 – 6.2 million]

• Deaths due to AIDS in 2005 2.8 million [2.4 – 3.3 million]

06/06 e 133
Regional HIV and AIDS statistics and features, 2003 and 2005
Adults (15+) and Adult (15-49) Adult (15+) and
REGION Adults (15+) and children prevalence child deaths due to
children living with HIV newly infected with HIV (%) AIDS
2005 2003 2005 2003 2005 2003 2005 2003
24.5 million 23.5 million 2.7 million 2.6 million 6.1 6.2 2.0 million 1.9 million
Sub-Saharan Africa [21.6‒27.4 [20.8‒26.3 [2.3‒3.1 million] [2.3‒3.0 million] [5.4‒6.8] [5.5‒7.0] [1.7‒2.3 million] [1.7‒2.3 million]
million] million]
North Africa and 440 000 380 000 64 000 54 000 0.2 0.2 37 000 34 000
Middle East [250 000‒720 [220 000‒620 [38 000‒210 000] [31 000‒150 000] [0.1‒0.4] [0.1‒0.3] [20 000‒62 000] [18 000‒57 000]
000] 000]
8.3 million 7.6 million 930 000 860 000 0.4 0.4 600 000 500 000
Asia [5.7‒12.5 million] [5.2‒11.3 million] [620 000‒2.4 [560 000‒2.3 [0.3‒0.6] [0.2‒0.6] [400 000‒850 [340 000‒710
million] million] 000] 000]
78 000 66 000 7200 9000 0.3 0.3 3400 2300
Oceania [48 000‒170 000] [41 000‒140 000] [3500‒55 000] [4300-69 000] [0.2‒0.8] [0.2‒0.7] [1900‒5500] [1300‒3600]

1.6 million 1.4 million 140 000 130 000 0.5 0.5 59 000 51 000
Latin America [1.2‒2.4 million] [1.1‒2.0 million] [100 000‒420 [95 000‒310 000] [0.4‒1.2] [0.4‒0.7] [47 000‒76 000] [40 000‒67 000]
000]
330 000 310 000 37 000 34 000 1.6 1.5 27 000 28 000
Caribbean [240 000‒420 [230 000‒400 [26 000‒54 000] [24 000‒47 000] [1.1‒2.2] [1.1‒2.0] [19 000‒36 000] [19 000‒38 000]
000] 000]
Eastern Europe and 1.5 million 1.1 million 220 000 160 000 0.8 0.6 53 000 28 000
Central Asia [1.0‒2.3 million] [790 000‒1.7 [150 000‒650 [110 000‒440 [0.6‒1.4] [0.4‒1.0] [36 000‒75 000] [19 000‒39 000]
North America, million] 000] 000]
Western and Central 2.0 million 1.8 million 65 000 65 000 0.5 0.5 30 000 30 000
[1.4‒2.9 million] [1.3‒2.7 million] [52 000‒98 000] [52 000‒98 000] [0.4‒0.7] [0.3‒0.6] [24 000‒45 000] [24 000‒45 000]
Europe
38.6 million 36.2 million 4.1 million 3.9 million 1.0 1.0 2.8 million 2.6 million
TOTAL [33.4‒46.0 [31.4‒42.9 [3.4‒6.2 million] [3.3‒5.8 million] [0.9‒1.2] [0.8‒1.2] [2.4‒3.3 million] [2.2‒3.1 million]
million] million]

06/06 e 134
 Estimated number of adults and children
newly infected with HIV, 2005
Western & Eastern Europe
Central Europe & Central Asia
North America 22 000 220 000
[150 000– 650 000] East Asia
43 000 [18 000 – 33 000]
[34 000 – 65 000] 97 000
Caribbean North Africa & Middle [55 000 – 290 000]
East
37 000 64 000 South & South-East
[26 000 – 54 000]
[38 000 – 210 000] Asia
Sub-Saharan Africa 830 000
Latin America 2.7 million [530 000 – 2.3 million]
Oceania
140 000 [2.3 – 3.1 million]
7200
[100 000 – 420 000]
[3500 – 55 000]

Total: 4.1 (3.4 – 6.2) million

06/06 e 135
 Estimated adult and child deaths from AIDS, 2005

Western & Eastern Europe

Central Europe & Central Asia
North America 12 000 53 000
[36 000 – 75 000] East Asia
18 000 [<15 000]
[11 000 – 26 000] 33 000
Caribbean North Africa & Middle [20 000 – 49 000]
East
27 000 37 000 South & South-East
[19 000 – 36 000]
[20 000 – 62 000] Asia
Sub-Saharan Africa 560 000
Latin America 2.0 million [370 000 – 810 000]
Oceania
59 000 [1.7 – 2.3 million]
3400
[47 000 – 76 000]
[1900 – 5500]

Total: 2.8 (2.4 – 3.3) million

06/06 e 136
Children (<15 years) estimated to be living with HIV, 2005

Western & Eastern Europe

Central Europe & Central Asia
North America 4000 6900
[3400 – 14 000]
11 000 [<8000] East Asia
[3500 – 27 000] 6400
Caribbean North Africa & Middle [2000 – 16 000]
East
22 000 31 000 South & South-East
[9800 – 43 000]
[12 000 – 75 000] Asia
Sub-Saharan Africa 170 000
Latin America 2.0 million [70 000 – 380 000]
Oceania
32 000 [1.5 – 3.0 million]
3000
[19 000 – 59 000]
[830 – 7900]

Total: 2.3 (1.7 – 3.5) million

06/06 e 137
 Estimated deaths in children (<15 years) from AIDS,
2005
Western & Eastern Europe
Central Europe & Central Asia
North America <100 1200
[620 – 2300]
<100 [<200] East Asia
[<200] 1400
Caribbean North Africa & Middle [530 – 2700]
East
3100 4900 South & South-East
[1600 – 5100]
[2000 – 9500] Asia
Sub-Saharan Africa 29 000
Latin America 330 000 [14 000 – 54 000]
Oceania
2900 [250 000 – 440 000]
600
[1800 – 4900]
[200 – 1800]

Total: 380 000 (290 000 – 500 000)

06/06 e 138
 Estimated number of children (<15 years)
newly infected with HIV, 2005
Western & Eastern Europe
Central Europe & Central Asia
North America 200 2300
[1400 – 3900]
500 [<400] East Asia
[<1000] 2300
Caribbean North Africa & Middle [1000 – 4100]
East
3700 6900 South & South-East
[2100 – 5800]
[3200 – 12 000] Asia
Sub-Saharan Africa 44 000
Latin America 470 000 [23 000 – 75 000]
Oceania
5000 [370 000 – 590 000]
1100
[3500 – 8000]
[400 – 2800]

Total: 540 000 (420 000 – 670 000)

06/06 e 139
 2005 global HIV and AIDS estimates
Children (<15 years)

• Children living with HIV 2.3 million [1.7 – 3.5

million]

• New HIV infections in 2005 540 000 [420 000 – 670

000]

• Deaths due to AIDS in 2005 380 000 [290 000 – 500

000]

06/06 e 140