2. Learning objectives
At the end of this module, you will be able to:
Describe the body’s general response
Differentiate between cellular and humoral response
Describe the difference between HIV infection and AIDS
Discuss the HIV epidemics globally, regionally, and locally in terms of number of people
affected
Define the terms: antibody and antigen
Uses assessment parameters for determining status of the immune system
Explain how “window period” may affect HIV testing results
Describe the progression of HIV infection 2
3. Immunity
Immunity: is the ability of the body to defend itself
against infectious agents.
Immunology: is the study of the body defense mechanism
against foreign invading agents
Immunity is essential for survival:
a. Defends us from bacteria, virus, and other pathogens
3
4. Immunity cont’d
b. Detects abnormal cells that periodically develop in life
and destroy them (e.g., cancer cells, tumor cells etc)
c. Ability to recognize non-self substances from self one’s
Types of immunity
i. Nonspecific immunity (innate immunity)
ii. Specific immunity(Acquired or Adaptive Immunity)
4
5. Innate (Nonspecific) Immunity
Non-specific is the 1st line of defense.
It distinguishes self antigen from non-self, but does not
distinguish one type of pathogen from another.
It can kill all types of pathogens.
Defense is inborn or natural, thus it does not need to be
exposed to the invader
Both external and internal defense
5
6. Innate immunity cont’d
• External
Skin
• Physical barrier to penetration by pathogens; secretions
contain lysozyme (enzyme that destroys bacteria)
Digestive tract
• High acidity of stomach
• protection by normal bacterial population of colon
6
7. Innate immunity cont’d
Respiratory tract
• Secretion of mucus
• movement of mucus by cilia
• alveolar macrophages
Genitourinary tract
• Acidity of urine
• vaginal lactic acid
7
8. Innate immunity cont’d
• Internal
Phagocytic cells
• Ingest and destroy bacteria, cellular debris, denatured
proteins, and toxins
Interferons
• Inhibit replication of viruses
Complement proteins
• promote destruction of bacteria
• enhance inflammatory response
8
9. Innate immunity cont’d
Endogenous pyrogen
• Secreted by leukocytes and other cells; produces fever
Natural killer (NK) cells
• Destroy cells infected with viruses, tumor cells, and
mismatched transplanted tissue cells
Mast cells
• Release histamine and cytokines that promote adaptive
immunity
9
10. Acquired immunity
Acquired immunity involves destruction of foreign invading
organisms by specifically producing sensitized lymphocytes
or antibodies
Lymphocytes are key players in acquired immunity.
Types of Acquired Immunity
Cell mediated immunity
Humoral (antibody mediated immunity)
Both types of acquired immunity are initiated by antigens
Immunization induces acquired immunity
10
11. Acquired immunity cont’d
Antigens:
- are gchemical substances (proteins, lipoproteins,
polysaccharides)
- located on the surfaces of foreign bodies
- are capable of inducing antibody production or sensitized
lymphocytes in the host body.
E.g. Antigens can be bacteria, virus, protozoan's, parasites,
insect venoms, pollen, transplanted organ
11
12. Acquired immunity cont’d
• Lymphocytes in acquired immunity
i. T-lymphocytes(helper T-cells, cytotoxicT-cells,
suppressor T-cells)
is responsible for “cell-mediated” immunity
ii. B-lymphocytes
is responsible for forming antibodies that provide
“humoral” immunity.
12
13. Types of T cells and their function
1. helper T cells,
2 . cytotoxic T cells, and
3 . suppressor T cells.
Helper T-cell(CD4+)
• most numerous of the T cells(3/4th)
• serve as the major regulator of virtually all immune
functions
13
14. Helper T-cell cont’d
When activated by antigens helper T-cells produces protein
mediators, called lymphokines, that act on other cells of the
immune system
Among the important lymphokines secreted by the helper T
cells are the following:
• Interleukin-2
• Interleukin-3
14
15. Helper T-cell cont’d
• Interleukin-4
• Interleukin-5
• Interleukin-6
• Granulocyte-monocyte colony-stimulating factor
• Interferon-gamma
In the absence of the lymphokines from the helper T
cells, the remainder of the immune system is almost
paralyzed.
15
16. Helper T-cell cont’d
acquired immunodeficiency syndrome (AIDS) virus,
inactivate or destroy helper T-cells
interleukin-2 stimulate both cytotoxic and suppressor T
cells & helper T-cells themselves
interleukins 4, 5, and 6 stimulate the B-lymphocyte
Lymphokines activate the macrophages to cause far
more efficient phagocytosis
16
17. Helper T-cell cont’d
Summary of functions of Helper T-cells
Stimulation of T- Cytotoxic and T- suppressor cells
Stimulation of B-cells to form plasma cells
Activation of the macrophage system etc.
17
18. Cytotoxic T(CD8+) Cells
• is a direct-attack cell capable of killing micro-organisms
• also called killer cells.
• it kill invaders by direct attack through the following methods:
1. They bore a hole through the membrane, so that electrolytes
and fluid enters and burst the microbes
2. They release toxic substances and kill invaders
•
18
19. Cytotoxic T-cells cont’d
• The cytotoxic cells also play an important role in
destroying
cancer cells,
heart transplant cells
Viral infected cells
other types of cells that are foreign to the person’s own
body.
19
20. Suppressor T cells
• Prevent the cytotoxic cells from causing excessive
immune reactions that might be damaging to the body’s
own tissues(immune tolerance)
20
21. Cell mediated immunity
• It is the responsibility of the T-lymphocytes
• The T-lymphocytes get activated when they are exposed to
antigen
The antigen is presented to the T-lymphocytes by antigen
presenting cells(APC)
• when exposed to antigen, the T lymphocytes proliferate and
release large numbers of activated, specifically reacting T
cells.
21
22. Cell mediated immunity cont’d
Antigen presenting cells(APCs)
• The three major types of antigen-presenting cells are
macrophages, B lymphocytes, and dendritic cells.
• The APC phagocytize antigens and partially broke it down
into smaller peptide fragments
The resulting digested fragments then bind to major
histocompatability complex(MHC) proteins inside the
APCs.
22
23. • The fragment-MHC complex is then transported to the
cell surface of APCs.
• helper T cell binds to this complex and get activated.
• The MHC proteins are encoded by a large group of
genes called the major histocompatibility complex
(MHC).
23
24. Health History
The history should note the patient’s age along with
information about past and present conditions and events
that may provide clues to the status of the patient’s
immune system.
24
25. Assessing for Immune Dysfunction
Be alert for the following signs and
symptoms:
Respiratory System
Changes in respiratory rate
Cough (dry or productive)
Abnormal lung sounds
(wheezing, crackles, rhonchi)
Rhinitis
Hyperventilation
Bronchospasm
Cardiovascular System
Hypotension
Tachycardia
Dysrhythmia
Vasculitis
Anemia
Gastrointestinal System
Hepatosplenomegaly
Colitis
Vomiting
Diarrhea
25
26. • Genitourinary System
Frequency and burning on urination
Hematuria
Discharge
• Musculoskeletal System
Joint mobility, edema, and pain
• Skin
Rashes
Lesions
Dermatitis
Hematomas or purpura
Edema or urticaria
Inflammation
Discharge
• Neurosensory System
Cognitive dysfunction
Hearing loss
Visual changes
Headaches and
migraines
Ataxia
Tetany 26
27. Physical Assessment
On physical examination the skin and mucous
membranes are assessed for lesions, dermatitis, purpura
(subcutaneous bleeding), urticaria, inflammation, orany
discharge.
Any signs of infection are noted.
The patient’s temperature is recorded, and the patient is
observed for chills and sweating.
27
28. The anterior and posterior cervical, axillary, and inguinal lymph nodes
are palpated for enlargement; if palpable nodes are detected, their
location, size, consistency, and reports of tenderness on palpation are
noted.
Joints are assessed for tenderness, swelling, increased warmth, and
limited range of motion.
The patient’s respiratory, cardiovascular, genitourinary,
gastrointestinal, and neurosensory systems are evaluated for signs
and symptoms indicative of immune dysfunction.
Any functional limitations or disabilities the patient may have are also
assessed. 28
29. Diagnostic Evaluation
A series of blood tests and skin tests and a bone marrow biopsy
may be performed to evaluate the patient’s immune competence.
Various laboratory tests may be performed to assess immune
system activity or dysfunction.
The studies assess leukocytes and lymphocytes, humoral
immunity, cellular immunity, phagocytic cell function,
complement activity, hypersensitivity reactions, specific antigen–
antibodies, or human immunodeficiency virus (HIV) infection.
29
30. Humoral (Antibody-mediated) Immunity Tests
B-cell quantification with monoclonal antibody
In vivo immunoglobulin synthesis with T-cell subsets
Specific antibody response
Total serum globulins and individual immunoglobulins
(electrophoresis, immunoelectrophoresis, single radial
immuneodiffusion, nephelometry, and isohemagglutinin
techniques).
30
31. Cellular (Cell-mediated) Immunity Tests
Total lymphocyte count
T-cell and T-cell-subset quantification with monoclonal
antibody
Delayed hypersensitivity skin test
Cytokine production
Lymphocyte response to mitogens, antigens, and
allogenic cells
Helper and suppressor T-cell functions
31
32. Autoimmune Diseases
•When the immune system attacks the body's own cells, it produces an
autoimmune disease.
• Some examples of autoimmune diseases include:
Type I diabetes attacks insulin-producing cells.
Rheumatoid arthritis attacks connective tissues around joints.
Myasthenia gravis attacks neuromuscular junctions.
Multiple sclerosis (MS) destroys functions of brain and spinal cord neurons.
Some autoimmune diseases are treated with medications that alleviate
specific symptoms.
33. Immunological Problems & Diseases
There are several ways in which the immune system may fail:
• When the pathogen is too violent (multiplies too fast, causes too much damage), or
evades the immune system (e.g., via mutation). Solution: vaccination or medication.
• Immune deficiencies: inherited or acquired.
• Improper response to foreign (non-pathogenic) antigens: Hypersensitivity and Allergy.
• Improper response to self: Autoimmune diseases.
• Rejection of transplanted tissues.
• Failure to detect cancers.
• [Cancer of immune cells.]
34. Immune Deficiencies
• Inherited:
Cellular - when the defective gene is only in T cells;
Humoral - when the defective gene is only in B cells;
Combined - when the defect is in a gene common to all
lymphocytes, e.g., RAGs (recombination activation genes).
35. • Acquired - due to:
• Hemopoietic diseases;
• Treatments: chemotherapy, irradiation;
• Infection: AIDS - caused by the Human Immunodeficiency Virus (HIV)
which attacks helper T cells.
• The virus gradually kills more T cells than the body can produce, the
immune system fails, and the patient dies from infections that are
normally not dangerous.
35
36. Immune Hypersensitivity
• Hypersensitivity is an improperly strong response.
• Immediate hypersensitivity:
• Mediated by antibodies.
• Types:
allergy - up to anaphylactic shock.
Induction of antibody-mediated cytotoxicity.
Sickness due to accumulation of immune complexes.
37. • Delayed hypersensitivity:
• Mediated by T cells.
• Hyper-activity of CTLs and macrophages.
• Contact sensitivity.
37
38. Allergy
• Allergy is an immune response to harmless antigens.
• Mechanism: IgE bind FCE receptors on mast cells
and basophils, and causes release of granules with
inflammatory agents.
• The “real” role of IgE is probably to fight parasites
such as helminths. (In developing countries, people
hardly ever suffer from allergies.)
39. Autoimmune diseases
• Normally, the immune system does not attack the self.
• This is ensured by elimination of auto-reactive lymphocytes during their
development (negative selection).
• However, there is a large group of diseases in which the immune system
does attack self-cells: autoimmune diseases.
• The attack can be either humoral (by auto-antibodies) or cellular (by
auto-reactive T cells).
• The attack can be directed either against a very specific tissue, or to a
large number of tissues (systemic autoimmune disease), depending on the
self-antigen which is attacked.
41. • Systemic: Immune complexes accumulate in many tissues and cause
inflammation and damage.
Systemic Lupus Erythematosus (anti-nuclear antibodies): harms kidneys,
heart, brain, lungs, skin…
Rheumatoid Arthritis (anti-IgG antibodies): joints, hearts, lungs, nervous
system…
Rheumatic fever: cross-reaction between antibodies to streptococcus and
auto-antibodies.
41
42. What could cause the immune system to attack the self?
• Changes in self-antigens, that make them look like non-self to the immune system, due
to:
• Viral or bacterial infection
• Irradiation
• Medication
• Smoking …
• Changes in the immune system:
• Normal auto-antibodies exist; mutations in B cells producing them may create
pathogenic auto-antibodies.
• Problems with control of lymphocyte development and differentiation.
44. Type I Hypersensitivities: Immediate IgE-Mediated
IgE antibody, mast cells/ basophils and its’ mediators (type I) hypersensitivities
Characterized by immediate reaction of the sensitized individual
Generally within minutes of exposure
Tendency to have type I hypersensitivities is inherited
Reactions occur in at least 20% to 30% of population
Allergen exposure, sensitization and re-exposure
Target organ immediate reactions
Clinical allergy: atopic diseases, drug allergy, insect allergy and anaphylaxis
46. Principle treatments in Type II
• ABO matching
• For AIHA, ITP: Steroid, immunosuppressive agents, +/- splenectomy
47. Type III Hypersensitivity
• Mechanisms: Ag (protein, drugs) + Ab (IgG, IgM) --> Immune complex
• Immune complex diseases:
• Serum sickness
• Autoimmune diseases: prototype-SLE
• Vasculitis
48. Principle treatments in Type III
Serum sickness: Avoidance of heterogeneous protein injection:
ERIG antirabies (equine rabies immunoglobulin (ERIG).
Autoimmune diseases: SLE
Avoidance sun exposure
Steroid
Immunosupressive agents
49. Type IV Hypersensitivity
• Delayed-type cell-mediated reaction
• Mechanism: Antigen (contactants) --> sensitized T-lymphoctyes --> re-exposure
--> T cells activation --> cytokines ---> mononuclear cell recruitment --> DTH
• Clinical disorder: Atopic contact dermatitis
Principle treatments in Type IV
• Avoidance
• Topical steroid
• Systemic steroid, if severe
50. Immunodeficiency
It is the absence or failure of normal function of one or more elements of the
immune system
Results in immunodeficiency disease
Can be specific or non specific
Specific = Abnormalities of B & T cells
Non specefic = Abnormalities of non specific components
PRIMARY OR SECONDARY
50
51. PRIMARY IMMUNODEFICIENCIES
Primary immunodeficiencies are inherited defects of the immune system
These defects may be in the specific or nonspecific immune mechanisms
They are classified on the basis of the site of lesion in the developmental or
differentiation pathway of the immune system
52. B CELL DEFICIENCY
X liked a gammaglobuinemia
IgA deficiency
IgG subclass deficiency
Immunodeficiency with increased Igm
Common variable immunodeficiency
Transient hypogammaglobulinemia of infancy
53. 1- X-linked a gammaglobulinaemia
In X-LA early maturation of B cells fails
Affect males
Few or no B cells in blood
Very small lymph nodes and tonsils
No Ig
Small amount of Ig G in early age
Recurrent pyogenic infection
54. 2- IgA and IgG subclass defeciency
IgA deficiency is most common
Patients tend to develop immune complex disease
About 20% lack IgG2and IgG4
Susceptible to pyogenic infection
Result from failure in terminal differentiation of B cells
55. 3- Immunodfeiciency with increased IgM (HIgM)
Results in patients with IgA and IgG deficiency
Production of large amount of IgM >200mg/dl of polyclonal IgM
Susceptible to pyogenic infection
Treatment by iv gamma globulin
Formation of IgM to neutrophils, platelets and other blood components
Due to inability of B cells to isotype switching
56. 4- Common Variable Immunodeficiency (CVID)
There are defect in T cell signaling to B cells
Acquired a gammaglobulinemia in the 2nd or 3rd decade of life
May follow viral infection
Pyogenic infection
80% of patients have B cells that are not functioning
B cells are not defective. They fail to receive signaling from T lymphocytes
Unknown
57. 5- Hypogamaglobulinaemia of infancy
Due to delay in in IgG synthesis approximately up to 36 months
In normal infants synthesis begins at 3 months
Normal B lymphocytes
Probably lack help of T lymphocytes
58. DISORDERS of T CELLS
• DiGeorge's syndrome:
It the most understood T-cell immunodeficienc
Also known as congenital thymic aplasia/hypoplasia
Associated with hypoparathyroidism, congenital heart disease, fish shaped
mouth.
Defects results from abnormal development of fetus during 6th-10th week of
gestation when parathyroid, thymus, lips, ears and aortic arch are being formed
59. T cell deficiencies with variable degrees of B cell deficiency
1- Ataxia-telangiectasia:
• Associated with a lack of coordination of movement (ataxis) and dilation of
small blood vessels of the facial area (telangiectasis).
• T-cells and their functions are reduced to various degrees.
• B cell numbers and IgM concentrations are normal to low.
• IgG is often reduced
• IgA is considerably reduced (in 70% of the cases).
60. 2- Wiskott-Aldrich syndrome:
Associated with normal T cell numbers with reduced functions, which get
progressively worse.
IgM concentrations are reduced but IgG levels are normal
Both IgA and IgE levels are elevated.
Boys with this syndrome develop severe eczema.
They respond poorly to polysaccharide antigens and are prone to pyogenic
infection.
61. Defects of the phagocytic system
Defects of phagocytic cells (numbers and/or functions) can lead to increased
susceptibility to a variety of infections.
1- Cyclic neutropenia:
It is marked by low numbers of circulating neutrophil approximately every three
weeks.
The neutropenia lasts about a week during which the patients are susceptible to
infection.
The defect appears to be due to poor regulation of neutrophil production.
62. 2- Chronic granulomatous disease (CGD):
CGD is characterized by marked lymphadenopathy, hepato- splenomegaly and
chronic draining lymph nodes.
• In majority of patients with CGD, the deficiency is due to a defect in NADPH
oxidase that participate in phagocytic respiratory burst.
63. 3- Leukocyte Adhesion Deficiency:
Leukocytes lack the complement receptor CR3 due to a defect in CD11 or
CD18 peptides and consequently they cannot respond to C3b opsonin.
Alternatively there may a defect in integrin molecules, LFA-1 or mac-1 arising
from defective CD11a or CD11b peptides, respectively.
These molecules are involved in diapedesis and hence defective neutrophils
cannot respond effectively to chemotactic signals.
64. 4- Chediak-Higashi syndrome:
• This syndrome is marked by reduced (slower rate) intracellular killing
and chemotactic movement accompanied by inability of phagosome
and lysosome fusion and proteinase deficiency.
• Respiratory burst is normal.
• Associated with NK cell defect, platelet and neurological disorders
65. Diagnosis
Is based on enumeration of T and B cells and immunoglobulin
measurement.
Severe combined immunodeficiency can be treated with bone marrow
transplant
67. Secondary: These disorders generally develop later in life
and often result from use of certain drugs or from another
disorder, such as diabetes or human immunodeficiency
virus (HIV) infection.
They are more common than primary immunodeficiency
disorders.
Some immunodeficiency disorders shorten life span.
Others persist throughout life but do not affect life span,
and a few resolve with or without treatment.
67
68. Secondary immunodeficiency disorders
• These disorders can result from
Prolonged (chronic) and/or serious disorders such as diabetes or cancer
Drugs
Rarely, radiation therapy
• Immunodeficiency disorders may result from almost any prolonged serious
disorder.
• For example, diabetes can result in an immunodeficiency disorder because white
blood cells do not function well when the blood sugar level is high.
• Human immunodeficiency virus (HIV) infection results in acquired
immunodeficiency syndrome (AIDS), the most common severe acquired
immunodeficiency disorder.
68
69. Symptoms
Respiratory infections (such as sinus and lung infections
Infections of the mouth, eyes, and digestive tract
chronic gum disease (gingivitis) and frequent ear and skin
infections
Many people have fevers and chills and lose their appetite
and/or weight.
Abdominal pain may develop, possibly because the liver
or spleen is enlarged.
69
70. • Many types of cancer can cause an immunodeficiency
disorder.
• For example, any cancer that affects the bone marrow
(such as leukemia and lymphoma) can prevent the bone
marrow from producing normal white blood cells (B cells
and T cells), which are part of the immune system.
70
72. 72
Content Overview
What is HIV?
What is AIDS?
The HIV pandemic
HIV transmission
Window period
Stages of HIV infection
73. 73
What is HIV?
• Human: Infecting human beings
• Immunodeficiency: Decrease or weakness in the body’s ability to
fight off infections and illnesses
• Virus: A pathogen having the ability to replicate only inside a living
cell
74. Basic concepts of HIV/AIDS
What is HIV/AIDS?
HIV: Human Immunodeficiency Virus
AIDS: Acquired Immuno Deficiency Syndrome
Acquired: acquired, not inherited
Immuno: weakness the immune system
Deficiency: deficiency of certain WBCs in the immune system
Syndrome: a group of symptoms or illnesses as a result of HIV infection
74
75. Historical Back Ground
1981: AIDS was first recognized in USA among Homosexual males
PCP was seen among 5 homosexuals
Kaposi’s sarcoma was diagnosed in 26 homosexuals
1983: HIV virus was isolated from a patient with lymph -adenopathy
1984: HIV virus was clearly demonstrated to be the causative agent for AIDS
There are approximately 36.7 million people currently living with HIV in 2015.
10 millions of people have died of AIDS-related causes since the beginning of
the epidemic. 75
76. The HIV epidemic in Ethiopia
Prevalence refers to the total number of cases of a particular
disease or health condition existing in a population at a certain
point in time, or during a given period.
Incidence refers only to the numbers of new cases of a disease
or condition that are identified in a given period.
76
77. • In Ethiopia, there were an estimated 1.2 million PLHIV in 2010.
• Thus, the prevalence of HIV infection in Ethiopia in 2010 was estimated to be
2.4% of the general population (2.9% of all females and 1.9% of all males).
• Women and children are particularly affected by HIV/aids;
• In 2010, close to 60% of the PLHIV in the country were females (totaling around
700,000 women) and about 80,000 were children.
77
78. There is a marked variation in HIV infection
between regions in Ethiopia
78
79. 79
Types of HIV Virus
• There are two species of HIV, known as HIV-1 and HIV-2
• HIV 1
Most common in sub-Saharan Africa and throughout the world
Comprises several subtypes with different geographic distributions.
Groups M, N, and O
There are d/t groups of HIV-1:
Pandemic dominated by Group M (major), which is responsible for most of the
infections in the world
Group O (outlier), a relatively rare viral form found originally in Cameroon,
Gabon, and France
80. Conti…..
• The M group comprises eight subtypes, designated A, B, C, D, F, G,
H, and J
• Subtype C is the most common worldwide
• In Africa, >75% of strains are subtypes A, C & D
• Subtype B is predominant in USA, Canada, South America, western
Europe, and Australia.
• In Asia, subtypes C and B are predominant
80
81. Conti…..
HIV 2
Found primarily in west Africa: Mozambique & Angola, parts of
Europe and India
Less easily transmittable
Develops more slowly
MTCT is relatively rare
Most often found in West Central Africa
81
82. HIV 1 & HIV 2
Transmitted through the same route
Associated with similar opportunistic infections
HIV attacks white blood cells, attaching itself to cells with the help of
a specific surface protein called CD4
CD4 is present on T helper lymphocytes and macrophages and the
virus mainly infects these cells
82
84. HIV is Spherical shaped virus.
The most important parts of the virus are:-
Its viral envelop has many small spikes which consists of two important
glycopropteins gp41 and gp120
Which play an important role when the virus attaches to its host cells
The viral capsid( core ) which contains two single stranded viral RNA and an
important enzyme for the virus called reverse transcriptase enzyme
84
85. The reverse transcriptase enzyme plays an important step in the life cycle of
the virus.
It converts the single stranded viral RNA into double stranded DNA ( this
process is called reverse transcription)
85
86. Characteristics of HIV
HIV infect cells that express CD4 receptor molecules
Successful entry of the virus to a target cell also requires cellular co-receptors
A fusion co-receptor is designated CXCR5 for T-cell tropic stain and CCR4 for
monocyte-macrophage tropic strains
The receptor and co-receptors of CD4 cells interact with HIV’s gp-120 and gp-41
proteins during entry into a cell
86
87. Life Cycle of HIV: Replication
1) Attachment /binding and fusion of the virus to the host cells
The receptor and co-receptors of CD4 cells interact with HIV’s gp-120 and
gp-41 proteins during entry into a cell
2) Uncoatting of the viral capsid and release of Viral RNA into the cytoplasm of
the host cell( Fusion Viral envelope fuses with cell membrane, releasing
contents into the cell.
3) Reverse transcription: Viral RNA is concerted in to Double stranded DNA by
reverse transcriptase enzyme
87
88. Retroviruses, such as HIV, have RNA that is transcribed into DNA by the viral
enzyme reverse transcriptase upon entry into the cell.
(The ability of retroviruses to copy RNA into DNA earned them their name
because this process is the reverse of the usual transfer of genetic information,
from DNA to RNA.)
The DNA form of the retrovirus genome is then integrated into the cellular DNA
and is referred to as the provirus.
The viral genome is replicated every time the host cell replicates its DNA and is
thus passed on to daughter cells.
4) Translocation : viral DNA is Imported to cell nucleus
89. Conti…..
5) Integration of proviral DNA to host-cell DNA ( Viral DNA is inserted into
host cell chromosome by unique enzyme integrase(P32).
Integrated viral DNA may remain latent for years and is called a provirus.
6) Cellular activation causes transcription (copying) of HIV DNA back to RNA
Some RNA translated to HIV proteins
Other RNA moved to cell membrane
Replication: Viral DNA is transcribed and RNA is translated, making viral
proteins.
Viral genome is replicated. 89
90. Conti…
7) Viral Assembly :HIV assembled under cell membrane and buddes from cell (
New viruses are made).
8) Maturation : viral Proteases enzymes cleave longer proteins in to important
viral proteins and help to convert immature viral particle into and infectious
HIV (New viruses bud through the cell membrane).
90
94. AIDS and HIV ‘THE NATURAL HISTORY’
HIV POSITIVE PERSON
AIDS PATIENT
NORMAL PERSON
WINDOW PERIOD (3 MONTHS)
PROMISCOUS SEX
30% - 5 YRS 30% - 10 YRS 30% - 15 YRS 10% - > 15 YRS
95. Progression of HIV is different in different individuals
• Rapid progressors: After the initial infection patients progress fast and develop
OIs and die within 2-3 years. Account for 15 % of all patients
• Normal Progressors: After the initial primary infection patients remain health
for 6-8 years before they start having overt clinical manifestations: account for
80 % of all patients
• Patients who remain alive for 10-15 years after initial infection.
• In most the diseases might have progressed and there may be evidences of
immunodeficiency.
95
96. Conti…..
Long term survivors:. Patients who remain alive for 10-15 years after initial
infection.
In most the diseases might have progressed and there may be evidences of
immunodeficiency
96
97. What affects disease progression in HIV Infected individuals
Viral set point: The level of steady-state viremia (set-point) at six
months to one year after infection,
Has an important prognostic implication for progression of HIV disease
Those with a high viral set-point have faster progression to AIDS, if not
treated
Immune response
High CD8 slow progression
Low CD8 rapid decline 97
98. Conti…..
• Viral type; HIV 2 slow course
• Concomitant conditions
Malnutrition hastens the progression of HIV
Chronic infectious conditions e.g. Tuberculosis
98
99. Window period
The period after infection but before the test becomes positive.
Amount of time for your body to start making HIV antibodies.
The window period can be from 9 days to 3-6 months, depending on the person's
body and on the HIV-test that's used.
The immune system usually takes 3 to 8 weeks to make antibodies against HIV,
but tests differ in how early they are able to detect antibodies.
99
100. Window period
A few people will have a longer window period, so if you get a negative
antibody test result in the first 3 months after possible exposure, you should
get a repeat test after 3 months.
97% of people will develop antibodies in the first 3 months after they are
infected.
In very rare cases, it can take up to 6 months to develop antibodies to HIV.
Antibody tests cannot accurately identify infection during this time
Immediately contagious
100
101. Diagnosis and Laboratory monitoring of HIV
1. Serologic Tests :
a. HIV antibody tests :-detect antibodies formed by the immune system against
HIV
i. ELISA : used to be standard screening test for HIV
Tests for a number of antibody proteins in combination
A very sensitive test ( 99.5 % ), but not very specific
A positive result needs to be confirmed by Western blot for confirmation
The test need skilled personnel , takes several hours
101
102. Conti…..
ii. Western blot: is an excellent confirmatory test.
It has high specificity but relatively poor sensitivity
It should not be used for screening purpose
iii. Rapid HIV antibody testes
• Advantages:
Rapid tests have reasonably good sensitivity and specificity ( >99 % )
Easy logistically , does not need continuous water or electric supply
Can be done by less skilled personnel and the interpretation of results is easy
Test result can be made available in < 30 minutes 102
103. b. HIV antigen assays ( Tests )
i.P24 antigen capture assay: this test detects p24 viral protein in the
blood of HIV infected individuals.
This viral protein can be detected during early infection, before sero
conversion.
Thus this test is used to detect blood donors during the Window
period
103
104. Conti…..
2. DNA –PCR : Viral replication
Is an extremely sensitive test -can detect 1-10 copies of HIV proviral DNA
per ml of blood.
It uses PCR technology to amplify proviral DNA
This test is costly and needs sophisticated instruments and highly skilled
professional
It is highly sensitive and the chance of false positivity is high.
Hence it should not be used for making initial diagnosis of HIV infection.
104
105. Conti…..
• It is often used
i. To make early diagnosis of HIV in HIV exposed infants as serology tests are
unable to diagnose HIV till the infant is 18 months old.
ii. To diagnose or confirm virologic failure in patients who are not responding to
ART
iii. When there is indeterminate serology
105
106. Conti…..
3. CD4 T cell count : as CD4 cells play a crucial role in the body defense
mechanism.
measuring the amount of CD4 cells is an important indicator of the level of
immune suppression that a patient infected with HIV.
In patients with HIV CD4 count drops by an average of 50 -100 cells per year
Tells you the level of immune damage inflicted by HIV.
106
107. Conti…..
• It should never used to make diagnosis of HIV
• CD4 count may be variable depending on circumstances
Diurnal variation; High evening low at midnight
Inter current infection, use of steroids and stress could affect CD4
count
• Following the trend in CD4 count is us full in clinical decision making
• Percentage of CD4 count is useful in children below 6 years
107
108. Conti…..
• Importance’s of CD4 count
To decide eligibility of a patient for ART
To follow the progress of a patient on ART
To diagnose immunologic failure in patients who are not responding
well to ART
108
109. What are opportunistic infections?
An opportunistic infection is an infection caused by harmful infectious
agents, or pathogens (bacteria, viruses, fungi, parasites or protozoa),
That usually do not cause disease in a healthy person, i.e. one with an
immune system whose function is not impaired.
Opportunistic infections observed in PLHIV include a wide range of
diseases, from minor ailments like chronic skin itching to severe
diseases such as tuberculosis (TB).
109
110. Conti…..
When the CD4 count has decreased below 450 cells/mm³, a person
living with HIV will start to acquire some mild or moderate
opportunistic infections.
When the CD4 count has decreased below 200 cells/mm³, a person
living with HIV is highly likely to acquire severe opportunistic
infections.
CD4 cells reside primarily (although not exclusively) in the blood,
where they are most likely to encounter 110
111. WHO HIV clinical stages
Staging means categorizing the patient clinically into one of the four
WHO HIV stages.
It is useful to know these stages because it enables you clinically to
identify patients with mild and severe diseases associated with HIV.
111
112. WHO Clinical Staging of HIV Disease in Adults and Adolescents
• CLINICAL STAGE 1
• Asymptomatic
Persistent generalized lymphadenopathy(PGL)
(PGL-is defined as the presence of lymph node > 1cm,
In two extra inguinal sites and persisting for more than three months)
113. WHO Clinical Staging of HIV Disease in Adults and Adolescents
CLINICAL STAGE 2
Moderate unexplained weight loss (<10% of presumed or measured body weight)
Recurrent respiratory tract infections: sinusitis, tonsillitis, otitis media and pharyngitis)
Herpes zoster
Angular cheilitis
Recurrent oral ulceration
Papular pruritic eruptions
Seborrhoeic dermatitis
Fungal nail infections
114. Varicella Zoster Virus Disease: Epidemiology
Reactivation of VZV that had been latent in dorsal root ganglia since original
infection with VZV (chickenpox)
Herpes zoster occurs in 3-5% of adults and more prevalent in
immunocompromised and elderly
Incidence 15-25 times greater in HIV-infected than in general population
Can occur at any CD4 count
Advanced immunosuppression may change manifestations but does not
substantially change incidence
115. Varicella Zoster Virus Disease: Clinical Manifestations
Herpes zoster (shingles): prodrome of pain in affected dermatome, then
characteristic skin lesions in same dermatome
Extensive skin involvement or visceral involvement are rare
Progressive outer retinal necrosis may be seen, usually with CD4 count <50
cells/µL
Rapid progression and vision loss
Acute retinal necrosis due to peripheral necrotizing retinitis may occur at any
CD4 count (more often at higher CD4)
116. Varicella Zoster Virus Disease: Clinical Manifestations
Chickenpox: primary VZV infection, uncommon in adults and adolescents
Respiratory prodrome, then vesiculopapular lesions (face and trunk >
extremities)
In advanced immunosuppression, may persist for weeks
Reports of transverse myelitis, encephalitis, vasculitic stroke
117. Varicella Zoster Virus Disease: Diagnosis
Clinical diagnosis based on appearance of lesions
Viral culture or antigen detection from swabs from fresh lesion or tissue biopsy
122. WHO Clinical Staging of HIV Disease in Adults and Adolescents
• CLINICAL STAGE III
Unexplained severe weight loss (>10% of presumed or measured body weight)
Unexplained chronic diarrhea for longer than one month
Unexplained persistent fever (above 37.6°C intermittent or constant, for longer
than one month)
Persistent oral candidiasis
Oral hairy leukoplakia
123. CLINICAL STAGE 3 cont;
Pulmonary tuberculosis (current)
Severe bacterial infections (such as pneumonia, empyema, pyomyositis, bone
or joint infection, meningitis or bacteremia)
Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
Unexplained anemia (<8 g/dl), neutropenia (<0.5 × 109 per liter) or chronic
Thrombocytopaenia (<50 × 109 per litre)
124. Mucocutaneous Candidiasis: Epidemiology
Oropharyngeal and esophageal candidiasis are common
Most common in patients with CD4 count <200 cells/µL
Prevalence lower in patients on ART
Vulvovaginal candidiasis
Occurs in non-HIV-infected women; does not indicate immunosuppression
In advanced immunosuppression, may be more severe or recur more
frequently
Usually caused by Candida albicans; other species (especially C glabrata) seen
in advanced immunosuppression, refractory cases
125. Mucocutaneous Candidiasis: Clinical Manifestations
Oropharyngeal (thrush):
Pseudomembranous: painless, creamy white plaques on buccal or
oropharyngeal mucosa or tongue; can be scraped off easily
Erythematous: patches on anterior or posterior upper palate or tongue
Angular cheilosis
Esophageal: retrosternal burning pain or discomfort, odynophagia, fever; on
endoscopy, whitish plaques with or without mucosal ulceration
Vulvovaginal: creamy discharge, mucosal burning and itching
126. Mucocutaneous Candidiasis: Diagnosis
Oropharyngeal:
Usually clinical diagnosis
KOH preparation, culture
Esophageal:
Clinical, with trial of therapy
Endoscopy with histopathology and culture
Vulvovaginal:
Clinical diagnosis, KOH preparation
127. WHO Clinical Staging of HIV Disease in Adults and Adolescents
CLINICAL STAGE IV
HIV wasting syndrome
Pneumocystis pneumonia
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection (orolabial, genital or anorectal
of more than one month’s duration or visceral at any site)
Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
Extrapulmonary tuberculosis
128. CLINICAL STAGE IV cont;
Kaposi’s sarcoma
Cytomegalovirus infection (retinitis or infection of other organs)
Central nervous system toxoplasmosis
HIV encephalopathy
Extrapulmonary cryptococcosis including meningitis
Disseminated non-tuberculous mycobacterial infection
129. Progressive multifocal leukoencephalopathy
Chronic cryptosporidiosis (with diarrhoed)
Chronic isosporiasis
Disseminated mycosis (coccidiomycosis or histoplasmosis)
• Recurrent non-typhoidal Salmonella bacteraemia
• Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-
associated tumours
129
130. CLINICAL STAGE IV cont;
Invasive cervical carcinoma
Atypical disseminated leishmaniasis
Symptomatic HIV-associated nephropathy or symptomatic HIV-associated
cardiomyopathy
131. Pneumocystis jiroveci Pneumonia: Epidemiology
Caused by P jiroveci (formerly P carinii)
PCP may result from reactivation or new exposure
In immunosuppressed patients, possible airborne spread
Risk factors:
CD4 count <200 cells/µL
CD4% <15%
Oral thrush
Recurrent bacterial pneumonia
Unintentional weight loss
High HIV RNA
132. PCP: Clinical Manifestations
Progressive exertional dyspnea, fever, nonproductive cough, chest discomfort
Subacute onset, worsens over days-weeks (fulminant pneumonia is uncommon)
Chest exam may be normal, or diffuse dry rales, tachypnea, tachycardia
(especially with exertion)
Extrapulmonary disease seen rarely; occurs in any organ, associated with
aerosolized pentamidine prophylaxis
139. Cryptococcosis: Epidemiology
Caused by Cryptococcus neoformans
Most cases seen in patients with CD4 count <50 cells/µL
5-8% prevalence in HIV-infected patients in developed countries before
widespread use of effective ART
Incidence much lower with use of ART
140. Cryptococcosis: Clinical Manifestations
Subacute meningitis or meningoencephalitis
(most common presentation)
Fever, malaise, headache
Neck stiffness, photophobia, or other classic meningeal signs and symptoms in
25-35% of cases
Lethargy, altered mental status, personality changes (rarely)
Acute illness with nuchal rigidity, seizures, focal neurologic signs observed in
developing countries
141. Cryptococcosis: Clinical Manifestations
Disseminated disease is common: often pulmonary infection with or without
meningeal involvement
Cough, dyspnea, abnormal chest X ray
Skin lesions
Papules, nodules, ulcers, infiltrated plaques seen in disseminated disease
143. WHO Recommendation
A. Establish the mechanisms for collaboration
1.Set up a coordinating body for TB/ HIV activities effective at all levels
2.Conduct surveillance of HIV prevalence among tuberculosis patients
3.Carry out joint TB/HIV planning
4.Conduct monitoring and evaluation
B.DecreasetheburdenoftuberculosisinpeoplelivingwithHIV/AIDS
1.Establishintensifiedtuberculosiscase-finding
2.Introduceionizedpreventivetherapy.INH300mg/dfor6-9months.
3.Ensuretuberculosisinfectioncontrolinhealthcareandcongregatesettings
143
144. Conti…..
C. Decrease the burden of HIV in tuberculosis patients
1.ProvideHIVtestingandcounseling
2.IntroduceHIVpreventionmethods
3.Introduceco-trimoxazolepreventivetherapy
4.EnsureHIV/AIDScareandsupport
5.Introduceantiretroviraltherapy
144
146. Post-Exposure Prophylaxis (PEP)
PEP is the use of therapeutic agents to prevent infection following exposure to
a pathogen.
In the case of HIV, Post-exposure prophylaxis (PEP) is short-term
antiretroviral treatment to reduce the likelihood of HIV infection after
potential exposure.
The types of exposures include percutaneous (needle stick injury), splash,
bite, suspected sexual assaults.
For health-care workers, PEP commonly is considered for exposures to HIV
and Hepatitis B. 146
147. • The least expensive way to deal with a disease is via prevention.
• The implementation of standard Precautions with appropriate training and
monitoring is the number one priority.
• Although standard Precautions will decrease the need for PEP there are
“accidents” and unanticipated occupational exposure.
• PEP will be made available free of charge for accidental occupational
exposures for health workers and emergency personnel as well as for rape
victims.
147
148. Risk of viral transmission with sharp injury from infected source
Source Risk (%) Source Risk (%)
HBsAg+ 30
HCV 1.8
HIV 0.3 0.3
148
The risk of transmission of HIV is much less than that of Hepatitis B by a factor of 100.
These transmission rates apply to occupation risk due to sharp injury.
149. Cotrimoxazole treats
The most commonly used prophylactic drug for HIV/AIDS is cotrimoxazole.
A wide-spectrum antibiotic that targets the pathogens causing the most common
opportunistic infections.
Pneumocysitiscarni/ jerovecipneumonia (PCP)
Streptococcus pneumonia
Isosporabelli (causes of entritis)
Toxopasmosis
Malaria (plasmodium falciparum)
Shigellosis 149
150. Criteria for starting cotrimoxazole prophylaxis by adult
All HIV-positive people at WHO clinical stages 2, 3, 4,
Or with a CD4 count less than 350 cells/mm³, should start
cotrimoxazoleprophylaxis.
The drug regimen for cotrimoxazoleprophylaxis is two 480 mg tablets, or one
960 mg tablet daily.
150
151. Duration of cotrimoxazole prophylaxis for adult PLHIV
If a person living with HIV has no access to HIV treatment,
cotrimoxazoleprophylaxis should be taken for the rest of the patient’s life.
If the patient has access to antiretroviral therapy (ART) for HIV,
cotrimoxazoleprophylaxis should be stopped when the CD4 count has
increased to 350 cells/mm³ and remains above that level for at least six
months.
151
152. Key Elements of Post-Exposure Prophylaxis (PEP) Programs
• Medical knowledge
• Indications
• Regimens
• Follow-up
• Programmatic readiness
• Awareness of need
• Timely availability of medical evaluation and PEP agents
• Availability of follow-up
• Confidentiality and documentation
153. Key Elements
1. Assess Risk
2. Manage Exposure
3. Determine HIV Status of source, when possible
4. Dispense PEP if indicated
5. Educate and Counsel Exposed Patient
6. Documentation
155. Community Needlestick Injuries
• Consider:
• HIV prevalence in the community
or facility
• Surrounding prevalence of
injection drug use
• Do not test discarded needles
for HIV
• False negatives
• Risk
Non-risky Fluids*
• Saliva, sputum or nasal secretions
• Tears
• Sweat
• Urine
• Stool
• Emesis
*Unless there is visible blood
157. PEP of Non-Occupational Exposures
PEP recommended if source HIV+, high-risk,
unknown (e.g. sexual assault)
PEP NOT recommended
Unprotected vaginal/anal intercourse
(receptive or insertive)
Unprotected receptive penile-oral contact with
ejaculation
Oral-vaginal contact with blood exposure
Needle-sharing
Injury with blood exposure
needlestick, bite, accident
Consider PEP when:
Blood exposure to biter and/or bitten person
(e.g. source has bleeding gums or lesions)
Blood exposure unknown
Kissing, or oral-oral contact & no mucosal
damage
Bites without blood
Needles/sharps exposure not in contact with
HIV + or at-risk person
Mutual masturbation – intact skin
Oral-anal contact
Receptive penile-oral contact without
ejaculation
Insertive penile-oral contact
Oral-vaginal – no blood exposure
158. 2. Exposure Management
•Wash immediately w/ soap and water
•Flush mucous membranes with water
•No evidence that use of antiseptics or expressing fluid reduces potential
transmission
•Antiseptics not indicated; caustic agents (bleach) not recommended
•“Milking the wound” may increase risk
•increases local inflammation
159. 4. PEP Recommendations
PEP ideally within 2 hrs, no later than 36 hrs from exposure
HAART (3 antiretroviral drugs) x 4 weeks
Baseline HIV serology of exposed person within 72 hours of initiating PEP
HIV specialist follow-up within 72 hours
PEP Recommendations Beyond 36 Hours?
“Decisions regarding initiation of nPEP beyond 36 hours post exposure should be made by the
clinician in conjunction with the patient with the realization of diminished potential for success
when timing of initiation is prolonged”1
Consider likelihood of HIV transmission
160. Preferred PEP Regimen
Zidovudine (AZT) 300 mg po bid
Lamivudine (3TC) 150 mg po bid
PLUS
Tenofovir 300 mg po daily with food
OR
Zidovudine 300 mg po bid
PLUS
Tenofovir 300 mg PO qd
Emtricitabine 200mg po qd
Combivir 1 po bid
Truvada 1 po qd
161. CDC: Basic HIV PEP Regimen
•zidovudine (ZDV) + lamivudine (3TC) or
emtricitabine (FTC)
•ZDV 300 mg BID; 3TC 300 QD or 150 BID; FTC
200 QD
•tenofovir (TNF) + lamivudine (3TC) or
emtricitabine (FTC)
•TNF 300 mg QD// 3TC 300 QD or 150 BID; FTC
200 QD
•lopinavir/ritonavir (LPV/RTV) (or efavirenz
Medication Side Effects
• Nausea
• Vomiting
• Fatigue
• Headache
• Loss of appetite
• Diarrhea
162. Antiretroviral therapy
Learning objectives
By the end of this session you expected to:
Demonstrate how to prepare a patient for ART initiation
Describe the requirements for ART initiation
Discuss when and what to start first line ARV regimen
Describe what to expect in the first few months after ARV initiation
Describe common drug interactions that may occur in patients taking ARV
Describe how to monitor for treatment response, drug toxicity and Rx failure
162
163. Introduction ART
What is ART?
A-anti
R-retroviral
T-Therapy
ART is the treatment of HIV infected individual with anti-retroviral drug.
What is HAART?
H-Highly
A-Active
A-anti
R-retroviral
T- treatment 163
164. Goals of ART
• The goal of ART is to reduce the number of virus in the blood and increase the
number of CD4 as much as possible.
• NB: The virus can never be eradicated completely from the body; hence the
person should take the drugs forever, even if the symptoms have disappeared.
• NB: Since the virus cannot be eradicated safer sex should be practiced.
164
165. The benefits of ART
• The benefits of ART can be divided into three —
1. benefits to PLHIV,
2. benefits to the health service,
3. benefits to the community at large.
165
166. Conti…..
Benefits of ART to the patient:
Prolongs life and improves quality of life.
Decreased stigma surrounding HIV infection
Households can stay intact, because patients survive for longer.
Businesses and jobs can stay intact for the same reason.
Reduces mother-to-child transmission of HIV.
Less money is spent on treating opportunistic infections and providing
palliative care (end-of-life care).
166
167. Conti…..
• Benefits of ART to the health service:
• Increased number of people who accept HIV testing and counselling.
• Increased motivation of health workers, since they feel they can do more for
PLHIV.
• Benefits of ART to the community:
• Decreased number of orphans.
• Increased awareness of HIV in the community, since more people accept HIV
counselling and testing.
167
168. Antiretroviral drugs (ARVs) and antiretroviral therapy (ART)
• Drugs that are used to treat HIV infection are called antiretroviral drugs,
which can be shortened to ARVs.
• Antiretroviral therapy (HIV treatment), also known as ART, is a treatment that
uses ARV drugs
168
169. The two main goals of ART are:
1 . To reduce the number of viruses in the patient’s blood to a very low level
2. To increase the number of CD4 lymphocytes in the patient as much as
possible, to increase the body’s immunity to infection, including immunity
against HIV.
169
170. Preparing patients for ART
Before people start ART, it is important to have a detailed discussion with them
about their willingness and readiness to initiate ART. The following issues should be
addressed during the preparation:
The likely benefits
Possible adverse effects
Provide information regarding lifelong treatment
The required follow-up and monitoring visits.
Detailed examination and treatment of OIs
Proper adherence counseling and support
-Education on safer sex practice and screening of family members 170
171. Requirements for initiation of ART
1. HIV positive test result with written documentation
2. Ensure that all adherence barriers are addressed
3. Start only patients with medical eligibility for ART
4. Any opportunistic infection has been screened and addressed according to
the standard guidelines
5. Ensure readiness of patient for ARV therapy
171
172. Summary of recommendations on when to start ART in adults, adolescents,
pregnant and breastfeeding women and children.
All Adults and
adolescents
a. HIV infection with CD4 count ≤500 cells/mm should be started on
HAART irrespective of WHO clinical stage.
b. HIV infection and WHO clinical stage 3 and 4 should be started on HAART
irrespective of CD4 cell count.
c. HIV infection and Active TB disease should be started on HAART
irrespective of CD4 cell count
d. All HIV positive pregnant and breast feeding women irrespective of CD4
count
e. Provide ART to all HIV infected partners of sero discordant
couple regardless of CD4 cell count (to reduce the risk of HIV
transmission to the negative partner)
172
173. Groups of ARV drugs
• There are three big groups of ARV drugs available in Ethiopia:
1 The NRTI drugs: this stands for ‘Nucleoside and Nucleotide Reverse
Transcriptase Inhibitors’ (divided into NsRTIsand NtRTIs).
2 The NNRTI drugs: this stands for ‘Non-Nucleoside Reverse Transcriptase
Inhibitors’.
3 The PI drugs: this stands for ‘Protease Inhibitors’.
173
176. How are antiretroviral drugs combined?
• A prescribed or recommended collection of medications intended to treat a
disease is called a treatment regimen (or simply a regimen).
• The regimens used in ART can be first line, second line.
176
177. Common first-line drug regimens for ART
•What ART regimen to start with (first-line ART)?
•Using simplified, less toxic and more convenient regimens as fixed-dose combinations is
recommended for first-line ART.
•Once-daily regimens comprising NRTI backbone (TDF + 3TC) and one NNRTI (EFV) are maintained
as the preferred choices in adults, adolescents and children
•AZT-3TC-NVP
•AZT-3TC-EFV
•d4T-3TC-NVP
•d4T-3TC-EFV
•TDF-3TC-EFV
•TDF-3TC-NVP
177
178. Classes and Dosages of anti-RVD for Adults and Adolescents and children currently used in
Ethiopia
Drug class/ drug Dose
Nucleoside RTIs
Abacavir (ABC) 300 mg twice daily
Lamivudine (3TC) 150 mg twice daily or 300 mg once daily
Zidovudine (ZDV) 300 mg twice daily.
Nucleotide RTI
Tenofovir (TDF) 300 mg once daily
Non-nucleoside RTIs
Efavirenz (EFV) 600 mg once daily
Nevirapine (NVP) 200 mg daily for the first 14 days, then 200 mg twice daily
Protease inhibitors
Lopinavir/ ritonavir (LPV/r) 400 mg/ 100 mg twice daily
Atazanavir /ritonavir(ATV/r) 300mg/100 once daily
178
179. WHY DO WE HAVE TO USE THE COMBINATION OF 3 ARV DRUGS?
It takes three drugs to have sustained viral suppression (low level of virus in the body).
HIV makes new copies of itself very rapidly.
Everyday billions of new copies of HIV are made and many infected cells die. Giving
a single drug might suppress viral replication for a short period of time but
resistance to the drug develops soon.
The same holds true to two drugs regimen and therefore giving two drugs alone for
treatment is strongly discouraged. Whenever
ART is given, it is administered as a minimum of three drugs combination referred as
HAART.
179
180. Antiretroviral drugs from different drug groups attack the virus in different ways.
Hitting two targets increases the chance of stopping HIV and protecting new cells
from infection.
Combinations of anti-HIV drugs may overcome or delay resistance.
Resistance is the ability of HIV to change its structure in ways that make ARV
drugs less effective.
HIV has to make only a single, small change to resist the effects of some drugs.
180
181. Second-line regimens
Many patients on ART will eventually develop failure of therapy, which means
the first-line regimen will not be effective anymore.
This is often because the drugs were not taken correctly, and this allowed HIV to
become resistant to them.
In that case, the doctor may decide to switch to a second line regimen, which is
more expensive.
Usually, the second-line regimen will consist of two NRTIs and one PI drug in
combination. 181
182. HIV/AIDS Prevention & Control Strategies
Risk reduction
Vulnerability reduction
Ensure the safety of the blood supply
Provide HIV-related information and education
Condom Promotion and Distribution
Management STIs
Care, Support and treatment
182
