HUMAN IMMUNODEFICIENCY VIRUS

1. HIV/AIDS
DR MD TIPU SULTAN
Associate Professor
Department of Microbiology
Chittagong Medical College
1

2. 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
2

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
3

4. HIV and AIDS
• 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
4

5. “The greatest single public
health challenge that
humanity has ever faced.”
Dr. Robert Lue, Harvard University
5

6. HIV/AIDS Historical
Perspective
1979
CDC reported unexplained PCP in 5 previously healthy,
homosexual men
 CDC reported Kaposi’s sarcoma in 26 previously healthy,
homosexual men
 Initially,then the disease was named as GRID (Gay
related immune deficiency)

1981- AIDS was recognized as separate disease
1981-1982

Increased association with IV drug use, recipients of
blood transfusions, hemophiliacs
6

7. HIV/AIDS Historical
Perspective
1983

Virus isolated.Then it was 1st named as
LAV(Lymphadenopathy associated virus)
1984

Virus was named as HTLV-III (Human T-cell
Lymphotrophic Virus)
1985

Virus was named as ARV (AIDS related Virus)
1986

Virus was named as HIV by the International
committee on the taxonomy of viruses
7

8. HIV/AIDS Historical
Perspective
1985
 ELISA
test developed
Today:
 Broad
spectrum of disease
 Asymptomatic
infection
 Clinical latency
 Advanced disease (AIDS)
 Clearly
sexually transmitted, and
transmitted through blood products
8

9. In Bangladesh, HIV positive
cases was 1st detected in
1989 in Chittagong
9

10. Global summary of the HIV and AIDS epidemic
Number of people living
with HIV
Total
39.4 million (35.9– 44.3 million)
37.2 million (33.8–41.7 million)
Adults
Women
17.6 million (16.3– 19.5 million)
Children under 15 years 2.2 million (2.0– 2.6 million)
People newly infected
with HIV
Total
4.9 million (4.3 – 6.4 million)
Adults
4.3 million (3.7 – 5.7 million)
Children under 15 years 640 000 (570 000 – 750 000)
AIDS deaths
Total
3.1 million (2.8 – 3.5 million)
Adults
2.6 million (2.3 – 2.9 million)
Children under 15 years 510 000 (460 000 – 600 000)
The ranges around the estimates in this table define the boundar within which the actual numbers lie, based on the best avail ble information.
ies
a
00003-E-1 – December 2004
10

11. HIV/AIDS
BANGLADESH SITUATION, END 2012
Total HIV-positive people - 2384
People living with AIDS - 676
Deaths due to AIDS
- 263
Sources:DGHS, MOH&FW, December 1, 2012.
WHO: Estimated to have 13,000 to 21,000 people
are likely to be infected with HIV.
11

12. Prevalence Among High Risk
Population in Bangladesh
•The highest prevalence is among IDUs 4%.
• Street and Hotel based CSWs– 0.2% each.
•Brothel based CSWs– 0.2% to 0.7%
• MSMs – 0.2%
12

13. Important
Bangladesh was the first among the SAARC
Countries to take the threat of HIV epidemic
seriously & initiated a national response in 1985.
According to WHO, Bangladesh is one of the
fortunate 111 countries where the infection rate
has not yet reached 1 adult / 1000.
13

14. Retrovirus
RNA virus
Enveloped
Reverse
transcriptase
enzyme
HIV, HTLV
14

15. Unique Characteristics of Retroviruses
Enveloped and encloses a capsid containing two copies
of RNA genome.
RNA-dependent DNA polymerase (reverse transcriptase)
and integrase enzymes are carried in the virion.
Replication proceeds through a DNA intermediate,
termed the provirus.
The provirus integrates randomly into the host
chromosome and becomes a cellular gene.
Simple retroviruses encode gag, pol, and env genes.
Complex viruses also encode accessory genes
(e.g., tat,
rev, nef, vif, vpu for HIV).
Virus assembles and buds from the plasma membrane.
Final morphogenesis of HIV requires protease cleavage
15
of gag and gag-pol polypeptides.

16. HIV Structure
HIV is composed of
three main layers:
 Envelope
 Viral Matrix
 Core
Image from
http://www.brown.edu/Courses/Bio_160/Projects1999/hiv/images/Virion2.jpg
16

17. HIV
structure
17

18. Types of HIV
HIV 1
Subtypes- A to I and O
Subtype A & D – found in sub Sahara
Africa
 Subtype B – found in US & Canada
 Subtype C – found in South Africa &
India
 Subtype E – found in south east Asia
 Subtype G & H - found in Russia &
Central Africa
 Subtype I – found in Cyprus

HIV 2
18

19. HIV-1 and HIV-2
• HIV-1 and HIV-2 are
• Transmitted through the same routes
• Associated with similar opportunistic
infections
 • HIV-1 is more common worldwide
 • HIV-2 is found in West Africa, Mozambique,
and Angola
19

20. HIV-1 and HIV-2
• HIV-2 is less easily transmitted
• HIV-2 is less pathogenic
• Duration of HIV-2 infection is shorter
20

21. Important antigens:
1) Group-Specific Antigens
p17: inner surface
p24: nucleocapsid
p9: nucleocapsid associated with RNA
GAG gene
21

22. 2) Type -Specific envelope glycoprteins
gp120 & gp41
ENV gene
22

23. 3. Enzymes
• Polymerase
(reverse
transcriptase)
• Integrase
• Protease
• POL gene
23

24. Transmission
of HIV
24

25. Transmission of
HIV
HIV is transmitted by
• Direct contact with infected blood
• Sexual contact: oral, anal, or vaginal
• Direct contact with semen or vaginal and
cervical secretions
• HIV-infected mothers to infants during
pregnancy, delivery, or breastfeeding
25

26. HIV enter the body via the bloodstream either during
sexual intercourse
needle drug abuse
transfusion with contaminated blood products
or via the placenta
During sexual intercourse, HIV 1 infects Langerhans dendritic
cells in the epithelium and these can then travel to lymph nodes.
On injection of virus into blood, the virus is likely to infect
dendritic and other monocyte-macrophage lineage cells.
26

27. Blood
Up to 10,000 infectious particles per
ml
Shared drug/drug-injecting
equipment
 needles,
syringes

28. Blood
Transfusions
 plasma,
whole blood, platelets
 clotting factors (decreased since 1985)
28

29. Sexual Contact
STD’s increase risk of transmission
 epidemiological
 exposed
trend
to one, may mean exposed to others
 inflammation
make person more
vulnerable to HIV invasion

30. Sexual Contact
Intercourse (without barrier)
 anal:
 vaginal:
 oral:

31. Sexual Contact
Semen: only 10-50 infectious virons per
ml
 artificial
insemination a risk
Vaginal/cervical secretions: less than 1
viron per ml

32. Perinatally
In utero (maternal-fetal circulation)
 HIV
crosses the placenta
During delivery
Breast-feeding
 low
incidence

33. Risk Factors
What you do not who you are
33

34. High risk groups
1)
2)
3)
4)
5)
homosexual/bisexual men
IV drug use/abuse
hemophiliacs
sex partners in abuse groups
infants of above groups
34

35. Transmission of HIV
HIV is not transmitted by
• Coughing, sneezing
• Insect bites
• Touching, hugging
• Water, food
• Kissing
• Public
baths
• Handshakes
• Work or school contact
• Using telephones
• Sharing cups, glasses,
plates, or other utensils
35

36. Important properties:
•HIV primarily infects CD4 T cells and cells of the
macrophage lineage
•Monocytes
•Macrophages
CD4 proteins on their surface
•Dendritic cells (skin)
•Microglial cells (CNS)
36

37. Which cells does HIV-1 infect?
Identification of molecular
targets.
Lymphocytes Receptor: CD4+,
Coreceptor: CXCR4
Macrophages: Receptor: CD4+
Coreceptor: CCR5
Dendritic cells (DC): DC recognized by gp120 on HIV
DC: primary target of mucosal infection!
DC present HIV antigen to resting lymphocytes
Microglial cells: Receptor: Galactosyl ceremide
37

38. Replication
38

39. HIV
chemokine
CD4
CD4
CCR5
CCR5
CD4
Mutant
CCR5
macrophage
Chemokine receptors are necessary co-receptors along with CD4 antigen
39

40. Provirus
40

41. 41

42. Pathogenesis
42

43. 43

44. Reduction in the numbers of CD4 T cells may result from
HIV-infected cytolysis, cytotoxic T-cell immune cytolysis.
The increased release of virus
into the blood as the numbers
of CD4 cells decrease gives
development of symptoms.
Macrophages may be spared the
cytolytic action of HIV because they
express less CD4 than T cells.
44

45. Macrophage-lineage cells express both the CCR5 & CXCR4
chemokine receptors and can be infected by M-& L-tropic HIV.
The virus reaches the lymph node
within 2 days of infection and there
the CD4 T cells are infected.
Macrophages are persistently
infected with HIV and are probably
the major reservoirs.
Continuous replication of the virus
occurs in the lymph nodes, with
subsequent release of the virus and
infected T cells into the blood
45

46. Pathogenesis(contd)
The hallmark of pathogenesis is the
profound immunodeficiency, primarily
affecting CMI
HIV infect any cells bearing CD4
receptor
-Severe depletion of CD4+ T-cell
-Impairment of function of surviving
CD4+ T-cell
46

47. Pathogenesis(contd)
Monocyte/Macrophage abnormalitiesRelatively resistant to cytolytic effect of HIV and
the consequences are
*Acts as reservoir of virus
*Transport the virus to different part of the body
B-cell abnormalitiesPolyclonal activation leads to hypergammaglobulinaemia
Unable to mount antibody response to a new antigen
due to lack of T cell help
47

48. Steps for pathogenesis of
HIV:
rapid early dissemination of virus
seeding of virus in lymphoid tissue
partial host immune responses that downregulates viral replication
sequestration of extracellular virus into
germinal center of lymph nodes
chronic activation of T lymphocytes and
secretion of immune system activating
cytokines
48

49. Steps for pathogenesis of
HIV:(cont.)
destruction of lymphoid tissue
escape of viral elements into peripheral
blood cells
direct killing of CD4 cells
49

50. Potential mechanism of CD4 T
cell depletion/dysfunction
Direct HIV mediated cytopathic effect
HIV mediated formation of syncytia
Virus specific immune response
Autoimmune mechanism
Anergy-Inappropriate cell signaling (gp120-CD4
interaction
Superantigen
Apoptosis
50

51. Three mechanisms by which
HIV evades immune system
1. Integration of viral DNA into host cell
DNA
resulting in a persistent infection.
2. A high rate of mutation of the env
gene.
3. Production of the Tat and Nef proteins that
downregulate class I MHC proteins required for
cytotoxic T cells to recognize and kill
HIV-infected cell
51

52. Progression of HIV in
the Body
Image from http://www.hivaidssearch.com/hiv-aids-links.asp?id=936
52

53. Initially, large burst of virus production &
viremia, which corresponds to the occurrence
of a mononucleosis-like syndrome.
53

54. Virus levels in the blood decrease during a
clinically latent period, but viral replication
continues in the lymph nodes.
54

55. Late in the disease, virus levels in the blood
increase, CD4 levels are significantly decreased.
the structure of the lymph nodes is destroyed,
and the patient becomes immunosuppressed
55

56. Clinical
Manifestations
56

57. Initial infection
Fever and other flu-like symptoms
 lympadenopathy
57

58. Prolonged Asymptomatic
Infection
person is HIV+ but asymptomatic
 lasts
for several years (subclinical)
 viral

replication occurring
up to 10 billion virons per day
 chronic
lymphadenopathy
58

59. Early Symptomatic
Disease
CD4 counts drop to 500-600 cells/ml
symptoms: recurrent fever, night
sweats, malaise, headache
physical findings: lymphadenopathy,
spleen enlarged, rash, weight loss
59

60. Opportunistic Infection
infection by a pathogenic organism
 that
is normally present but not harmful
 becomes infectious in
immunocompromised person
60

61. AIDS
AIDS vs. HIV positive
61

62. Average time between infection and
AIDS was 10 years
 time
has increased with new protease
inhibitors

63. Symptoms of HIV - “classic 6”
−
−
−
−
−
−
fatigue/malaise
lymphadenopathy
weight loss
fever
night sweats
diarrhea
63

64. AIDS
CD4 count less than 200/mm
majority of manifestations due to opportunistic
infections due to immunosuppression
 rather than direct injury by virus

It is a condition in which common curable
infectious disease turned into incurable form
due to immunodeficiency, caused by HIV
infection
64

65. Clinical Course of
HIV/AIDS
HIV Infection
Virus deposited on mucosal surface
 Acute infection (mono-like symptoms)
 Viral dissemination
 HIV-specific immune response
 Replication of virus
 Destruction of CD4+ lymphocytes
 Rate of progression is correlated with viral load

Latent Period
65

66. Clinical Course of
HIV/AIDS
AIDS
 Immunologic
dysregulation
 Opportunistic infections and cancers
 Risk of infections is correlated with number
of CD4+ lymphocytes
 Average patient with AIDS dies in 1-3
years
66

67. WHO classification of clinical
stages of infection
Children – Three stages
Adults & Adolescents – Four stages
67

68. WHO Clinical stage I
in Children
Asymptomatic
Generalized lymphadenopathy
68

69. WHO Clinical stage II
in Children
Unexplained chronic diarrhoea
Severe persistent or recurrent
candidiasis outside the neonatal
period
Weight loss or failure to thrive
Persistent fever
Recurrent severe bacterial infection
69

70. WHO Clinical stage III
in Children
AIDS – defining opportunistic
infections
Severe failure to thrive
Progressive encephalopathy
Malignancy
Recurrent septicaemia or meningitis
70

71. WHO Clinical stage I
in Adults & Adolescents
Asymptomatic
Persistent generalized
lymphadenopathy
Performance scale 1:
asymptomatic, normal activity
71

72. WHO Clinical stage II
in Adults & Adolescents
Weight loss, <10% of the body weight
Minor mucocutaneous manifestations
Herpes Zoster within the last 5 years
Recurrent upper respiratory tract
infections
Performance scale 2: symtomatic,
normal activity
72

73. WHO Clinical stage III
in Adults & Adolescents
Weight loss, >10% of the body weight
Unexplained chronic diarrhoea >1 month
Unexplained prolonged fever (interminant
or constant) >1 month
Oral candidiasis (thrush)
Pulmunary tuberculosis
Severe bacterial infection
Performance scale 3: bed-ridden, >50% of
the day during the last month
73

74. WHO Clinical stage IV
in Adults & Adolescents
HIV wasting syndrome
Pneumocystis carinii pneumonia
Toxoplasmosis of the brain
Cryptosporidiosis with diarrhoea
Cryptococcosis, extra pulmonary
Atypical mycobacteriosis
Salmonella septicaemia
Progressive multifocal leukoencephalopathy
Performance scale 4: bed-ridden, >50% of the
day during the last month
74

75. WHO Clinical stage IV
in Adults & Adolescents
(Cond.)
Cytomegalovirus disease of an organ other
than liver, spleen or lymph nodes.
Hepes simplex virus infection, mucateneous
>1 month, or visceral any duration
Progressive multifocal leukoencephalopathy
Any disseminated endemic mycosis
(I.e. histoplasmosis,
coccidiodomycosis)
Candidiasis of the oesophagus, trachea,
bronchi or lungs
Lymphoma
75

76. AIDS in
Children
76

77. AIDS in Children
Infants who are seropositive at 18
months are infected
Infants progress to AIDS more rapidly,
usually in 3 years
HIV testing during pregnancy
77

78. AIDS in Children
Transmission is usually perinatal
100% are HIV+ at birth
25% are actually infected
1
in 4 chance of passing on virus
 less if mother is treated
78

79. Opportunistic infections
− pneumocystic carinii pneumonia (PCP)
− candida esophagitis
-- cryptococcal meningitis
− chr. mucocutaneous Herpes simplex
-- toxoplasmosis
− disseminated Mycobacterium avium or kansasii
− disseminated CMV
-- chronic Cryptosporidial enterentis
− disseminated stronyoidiasis
-- Histoplasmosis
− bronchopulmonary candidiasis
-- Isosporiasis
-- disseminated TB
-- disseminated Coccidioidomycosis
− recurrent Salmonella septicemia
79

80. Opportunistic tumors
− Kaposi’s sarcoma
− primary CNS lymphoma
− certain high-grade B-cell lymphoma
80

81. Diagnosis
81

82. Laboratory diagnosis
Evidence of HIV infection
Virus isolation
Measurement of viral nucleic acid
Detection of viral antigen
Detection of viral antibody
Recognition of immunodeficiency
CD4+ T cell count
Recognition of AIDS related disease
82

83. 1.Virus isolation :
HIV can be cultured from lymphocytes
in peripheral blood.
(Co-culture of patients T-cell with Leukaemic
or mitogen stimulated CD4+ Tcell line).
83

84. 2. Detection of viral Nucleic Acid :
By RT-PCR
Branched-chain DNA
To detect viral RNA in clinical specimens.
84

85. Viral RNA Assay Dynamics of HIVbillions of viruses produced and
destroyed daily
 Rate
of viral replication stabilizes after
primary infection at a “set point: in each
individual. (102-106 HIV RNA copies/ml) of
plasma
 Remains stable over months and possibly
years
85

86. Viral RNA Assay (cont.)
Viral RNA - indirect reflection of the number
productively infected cells in the body as a
whole
Appears to be a proportion between plasma viral
RNA and the amount of viruses in the fixed
lymphoid tissues
 Set point associated with the rate of disease
progression and time of death
 HIV RNA levels appear more predictive of
progression than CD counts

4
86

87. 87

88. Therefore utility of HIV RNA
assays include:
 Assessing
baseline status in newly diagonal
HIV patient
 Assessing response to therapy
 Assessing development of resistance to current
therapy
 Typically 109-1010 virions are produced daily
 Reductions in plasma viremia correlates with
increased CD4 cells and AIDS-free survival
88

89. 3. Detection of HIV
Antigen
HIV antigen tests detect the presence
of HIV in blood
P24 antigen tests measure one of the
proteins found in HIV
The antigen often becomes undetectable after antibodies develop
and may reappear at low levels intermittently during the period
of clinical latency and in some people as infection progresses
89

90. 3. Detection of viral p24 Antigens:
Low levels of circulating HIV p24 antigen can be
detected in the plasma by ELISA soon after infection.
usually disappeared by 8-10 weeks after exposure.
It can be a useful marker in individuals who have been
infected recently
but have not had time to
mount an antibody response
90

91. 4. Detection of antibody
measuring antibodies by ELISA.
HIV antibody may develop slowly,
4-8 wks in most patients.
A positive test in a serum sample must be confirmed by a repeat test
If the repeat ELISA test is reactive, a confirmation test is performed.
By immunofluorescence, Western blot technique or
Line immunoblot assay
91

92. Detection of IgG antibody to envelope components(gp120
and its subunits)
This is the most commonly used marker of infection
The routine tests used for screening are based on ELISA techniques,
which may be confirmed with Western blot assays.
Up to 3 months may elapse from initial infection to
antibody detection (serological latency, or window period).
IgG antibody to p24 (anti-p24)
This can be detected from the earliest weeks of infection and
through the asymptomatic phase. It is frequently lost as disease
progresses.
92

93. Window period:
Early in infection when the blood of an infected
person can contain HIV but antibodies are not
detectable.
Seroconversion:
Development of evidence of
antibody response to a disease.
Viral Load:
The amount of HIV in the blood.
93

94. “Window Period”
 A period of 4-6 weeks after HIV exposure
when antibodies to HIV are not detectable
in the blood
 A person at high risk who initially tests
negative should be retested at 3 months to
confirm diagnosis
94

95. “Window Period”
Time between infection with HIV and
detection of HIV antibodies in the serum
(time to seroconvert)
“Seropositive”: detectable antibodies to
HIV in the serum
 person
becomes infectious within 2 weeks
of exposure

96. Seroconversion : detectable antibody response96

97. Tests which detect
antibodies
Enzyme linked immunosorbent assay (ELISA)
Particle agglutination test (PAT)
Screening tests
Latex agglutination test
Indirect fluorescence antibody test (IFAT)
Radio immunoprecipitation assay (RIA)
Immunochromatographic test (ICT)
Line immunoblot assay (LIA)
Western Blot assay (WB)
Confirmatory tests
97

98. ELISA for HIV antibody
ELISA false-positive:
immunologic abnormalities
neoplasms
multiple transfused
pregnancy
Microplate ELISA for HIV antibody: colored wells indicate
reactivity
98

99. Western Blot
HIV-1 Western Blot
Lane1 : Positive Control
Lane 2 : Negative
Control
Sample A: Negative
Sample B: Indeterminate
Sample C: Positive
99

100. Western blot to be considered positive
At least two bands including
p24, gp41, or gp120/gp160 should be present.
(antibodies to HIV proteins of specific molecular weight
can be detected)
Western blot is confirmatory test for HIV antibody
detection, because the test can detect all the HIV-specific
antibodies according to their molecular weight
100

101. 101

102. 5. CD4:CD8 cell count:
Absolute number of CD4+ cell and
ratio of helper cell to inducer cell are
abnormally low.
102

103. Selection of the HIV
Test
Is site-specific based on:
 National/local
policies
 Availability of supplies and laboratory
support
 Availability of trained personnel
 Evaluation of specific tests in the country
 Costs
103

104. The Testing Process
• Test sample
• Blood, saliva, urine
• Process the sample, on-site or in lab
• Obtain results
• Keep confidential
• Method determined by clinic protocols and
client
• Provide results to client
• Provide post-test counselling, support and
104

105. Guiding Principles for
Counselling and Testing
 Information on HIV status kept private
 Information shared only with providers
directly involved in care—and only on a
“need to know” basis
 Medical records kept in safe place
105

106. Guiding principles
(contd.)
• Pre-test Group education
• Informed Consent
• Identifies:
• Purpose of testing and processes involved
• Benefits and risks of testing
• Available treatment and support
• Respects
• Individual’s autonomy and right to confidentiality
106

107. Counseling and Testing as an
Entry Point to MCH/HIV
Prevention
Community action
to reduce Stigma
& discrimination
Post - delivery
care and support
Safer infant
feeding
Primary
prevention of new
HIV infection
VCT
and its links
with other
services
Prevention of
unintended
pregnancy
Safer obstetric
practices
Antiretroviral
prophylaxis
107

108. Pre-test Information
 Group education in
 Relevant HIV and AIDS information
 Transmission and prevention
 STIs and HIV
 HIV testing and test result interpretation
 Implications of both positive and negative results
 Benefits and risks of HIV testing
 Individual counselling and risk assessment
 Identification of supportive services
 Privacy and Confidentiality
108

109. Post-Test
Counselling
Provide the woman with her HIV test result
Help her understand what the result means
Provide support, information, and referral when
indicated
Encourage risk- reducing behavior
Encourage disclosure and partner testing
109

110. Post-Test
Counselling
 HIV-negative
 Review window period if indicated
• Prevent future infection
• Review risk with new infection
• Educate partner and encourage partner testing
110

111. Post-Test
Counselling
 HIV-positive result
• Clarify understanding
• Acknowledge feelings
• Review benefits of knowing HIV status
• Address immediate concerns
• Schedule follow-up visit
• Provide support ,name and telephone
number of contact person
111

112. Diagnosing HIV in HIVExposed Infant
 ARV prophylaxis reduces but does not eliminate
Mother to child transmission of HIV infection
 Since maternal antibodies cross the placenta,
antibody testing is not recommended prior to 18
months of age
 Infants who are breastfeeding require additional
testing 6 weeks after complete cessation of
breastfeeding
 HIV viral assays are not used for diagnosis of HIV
infection in the infant
112

113. Summary
• Pre-test information, HIV testing, and post-test
counselling should be available to all pregnant
women
• The need for pre-test counselling should be
determined on an individual basis
• The healthcare provider and the facility must
maintain confidentiality of HIV status.
• Partner testing and couples counselling should be
encouraged
113

114. Summary (contd.)
Rapid tests with same day results are the
recommended procedure for most settings.
Infant diagnosis is complex but important for
clinical management
•
Standard diagnosis is done by antibody test at 18 months
•
Earlier diagnosis is possible with PCR testing
Post-test counseling is important for all women,
including HIV-negative women
114

115. Disclosure
• Ensure confidentiality
• Respect woman’s choices
• Encourage partner testing
• Review prevention of transmission
• Identify support
115

116. CURRENT TESTING FACILITIES
IN BANGLADESH
Screening Purposes :
Latex agglutination
Immunochromatography
Particle agglutination
ELISA
For Confirmation :
BSMMU, Dhaka-Western blot
Dhaka-Western blot
ICDDR,B-Dhaka-Western blot
Dhaka-Western blot
Medical College-Line immunoassy, ELISA
Chittagong Medical College-Line immunoassy, ELISA
Sylhet Medical College-Line immunoassy, ELISA
AFIP,
IEDCR,
Dhaka
116

117. EXISTING DIAGNOSTIC FACILITIES ( CONTD)
Screening tests for HIV [ PAT and ELISA ] are also carried
out in blood transfusion centres to ensure safe blood
transfusion
Currently, 98 safe blood transfusion centres are present
in our country [ Medical Colleges- 13, Specialized hospitals
- 6, District hospitals- 53, CMH- 13, Other big hospital- 10,
Red crescent- 3 ]
117

118. Treatment
118

119. Types of HIV Drugs
Entry inhibitors
Reverse Transcriptase inhibitors
Integrase inhibitors (On study)
Protease inhibitors
Assembly & budding inhibitors
(On study)
120

120. Attacking HIV with antiretroviral drugs
Protease
inhibitors
Attachment
inhibitors
Assembly
inhibitors
RT
inhibitors
Integration
inhibitors
121

121. Entry inhibitors
Fusion inhibitor
Fuzeon (enfuvirtide, or T-20)
122

122. Reverse Transcriptase
Inhibitors
Nucleoside reverse transcriptase inhibitors
(NsRTIs)
 Zidovudine(ZDV, AZT)
 Didanosine (ddl)
 Stavudine (d4T)
 Lamivudine (3TC)
 Abacavir (ABC)
123

123. Reverse Transcriptase
Inhibitors(contd)
Non - nucleoside reverse transcriptase
inhibitors (NsRTIs)
Nevirapine (NVP)
 Efavirenz (EFZ)


Delavirdine
Nucleotide reverse transcriptase inhibitors

(NtRTIs)
Tenofovir disoproxil fumarate
124

124. Protease Inhibitors
Indinavir(IDV) - Crixivan
Nelfinavir(NFV) - Viracept
Ritonavir(RTV) - Norvir
Saquinavir(SQV) - Invirase or Fortovase
Amprenavir(APV) – Agenerase
Lopinavir/Ritonavir(LPV/r) - Kaletra
125

125. Therapy might be started when PVL is
over 10,000. If therapy is in progress,
several PVL tests a year monitor the
status. If PVL goes up, medication
needs to be changed, quite obviously.
The goal is to clear detectable virus
from the blood in 16-24 weeks.
126

126. Highly Active
Antiretroviral Therapy
(HAART)
Combination of three
or more drugs
127

127. Why is HIV so hard to
treat?
1.
HIV-1 and other lentiviruses have the unique
property among retroviruses to replicate in
nondividing cells.
2.
Mutation rate is maximum permissible
3.
Latent period of incubation
4.
Integration into host genome unpredictable
128

128. 4 Questions that Need Answers
for HIV Therapy
When to initiate therapy?
Which types of drugs to use?
When to change therapy?
Which drugs to use when changing
therapy?
129

129. When to Initiate Therapy?
2001
Recommended for patients with RNA > 30,000
copies/ml
 CD4 cell counts < 350/µl irrespective of RNA level.
 RNA levels 5000-30,000 and CD4 between 350500/µl

130

130. What Drugs should be
Initiated in Newly Diagnosed
HIV + Patient?
AZT
+ 3TC + either PI or NNRTI
131

131. Two strategies to maximize
benefits/minimize toxicities:
Alternating therapies
Combination therapy-demonstrated
more beneficial than monotherapy
 Decreased
emergence of resistance
 Decreased risk of toxicity
132

132. HIV infected Pregnant Female
Standard antiretroviral therapy should be used in the
HIV infected pregnant female

Possible risk of premature delivery (highest in non-treated
individuals)
133

133. Reduced transmission of
HIV from mother to infant
Proportion of infants of HIV (+) mothers
who acquired HIV
40
30
33
% 20
10
0
8
No ARV
With ARV
134

134. Pediatric Patients with HIV
Therapy:


AZT + 3TC + either PI (nelfinavir) or NNRTI (efavirenz)
Expanded access of liquid formulations


ddC zalcitabine (from Roche), efavirenz (from Dupont), Kaletra
(from Abbott)
Not recommended: overlapping toxicities or undesirable
effects





Monotherpay
d4T and AZT
ddC and ddI
ddC and d4T
ddC and 3TC
135

135. Reasons to Change Regimen?
Plasma HIV RNA levels measured on 2
separate occasions
CD4 count (changes in these counts)
Remaining treatment options for potency
Potential resistance patterns from prior
antiretroviral therapies
Potential for adherence/tolerance
Potential for side effects, drug interactions,
possible need to alter concomitant
medications
136

136. 3 Patient Populations
Identified as Needing
Therapeutic Changing
Patients receiving incompletely suppressive
therapy (single or double NRTI) with
detectable or undetectable plasma viral load
Patients who have been on potent
combination therapy and whose viremia was
initially suppressed to undetectable levels but
has again become detectable
Patients receiving potent combination therapy
and whose viremia was never suppressed to
below detectable limits
137

137. Goal of Therapy
Suppressing viremia to below
detectable levels as consistently as
possible.
 Requires
a level of commitment to be
adherent
 even a low level of non-adherence will
result in the development of resistance
which could render the therapy useless.
138

138. 139

139. Prevention
140

140. Prevention of HIV
Infections
Vaccines

Pre-clinical work in animals is promising
Education, Counseling & Behavior mod.

Worked in the US for homosexual men
Free needles for IV drug users

Societal debate
Improved blood supply

Greatly decreased risk for hemophiliacs
Screening and treating pregnant women

Area where interventions are well accepted
141

141. Why is HIV so hard to
fight?
Some antibodies that the body produces actually
work to enhance HIV replication.
Some antibodies that work to neutralize HIV
replication can become enhancing antibodies when
the virus mutates.
Cells other than helper T-cells can be infected,
therefore the virus can colonize many tissues of the
body.
HIV can kill cells that it doesn’t even infect.
142

142. Vaccine development is difficult
1. HIV mutates rapidly
2. Not expressed in all cells that are infected
& is not completely cleared by the host
immune response after primary infection.
3. Protective immunity are not known
4. Vaccine based on attenuated or inactivated
HIV or in simian isolates don’t ensure safety
against possible vector-induced disease
5. Lack of appropriate animal modal for HIV.
143

143. AIDS Vaccine
Two vaccines on trial
AIDSVAX B/B – tested in North
America & Amsterdam
 AIDSVAX B/E – tested in Thailand

Each mixed the surface proteins
(gp120) from two strains of HIV
144

144. New vaccines on human trial
tgAAC09 – begun in Belgium
Single shot vaccine
Uses Targeted Genetics ‘ rAAV
(recombinant adeno associated viral
vector) Technology
145

145. New DNA vaccines on human trial
Vaccine - ADVAX
Vaccine is tailored for C strain of HIV
Worked by The Aron Diamond AIDS
ResearchCenter & International AIDS
Vaccine initiative
Trail in New York & Rochester
Developed on synthetic DNA based on
the genetic material available
Safe to use
146

146. SURVEILLANCE
SYSTEM
IN BANGLADESH
Surveillance is carried out in phases.
Currently 4th round of HIV surveillance has been
done :
-Surveillance on high risk population
-Surveillance on mass population
No case has been detected on mass population
So emphasis should be given on high risk
population.
147

147. MOST PRESSING ISSUES
IN HIV/AIDS CONTROL
MEASURE IN
BANGLADESH
High numbers of migrant workers
Low socio-economic condition & illiteracy
High prevalence rate of STI among sex workers
Unsafe sex practice by sex workers
Sharing of needles by the IDUs
148

148. A Short Preview Of The Existing Guideline On
HIV/AIDS And STD Related Issues :
The government of Bangladesh has Formulated
Guidelines On The Following Specific Areas Related
To HIV/AIDS :
Epidemiological surveillance, Testing policy,
Infection management, Counseling , Safe blood
transfusion , Education , Information , Awareness
development , Promotion of preventive measures ,
Social science and behavioral research , Clinical
vaccine trial , Ethical and legal aspects
149

149. Thank you
150