Hepatitis Viruses

Hepatitis Viruses
• Many viruses cause hepatitis.
• Of these, five medically important viruses are commonly described as
“hepatitis viruses” because their main site of infection is the liver.
• These five are hepatitis A virus (HAV), hepatitis B virus (HBV),
hepatitis C virus (HCV), hepatitis D virus (HDV, delta virus),
and hepatitis E virus (HEV)
• Other viruses, such as Epstein–Barr virus, cytomegalovirus, and yellow
fever virus, infect the liver but also infect other sites in the body and
therefore are not exclusively hepatitis viruses.
• The hepatitis viruses are grouped together, not because of
structural or genetic similarities, but because they share the same tissue
tropism, which is the liver.
• Hepatitis is inflammation of the liver produced by autoimmune
disease, alcohol or drug abuse, genetic disorders, or microbial infection. 2
 Table: Comparative Features of Hepatitis Viruses
Feature Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Common name "Infectious" "Serum" "Non-A, non-B "Delta agent" "Enteric non-A,
post- non-B”
transfusion"
Family Picornaviridae Hepadnavirida Flaviviridae Deltavirus Hepeviridae
e
Virion 27 nm, 42 nm, 60 nm, 35 nm, 30–32 nm,
icosahedral spherical spherical spherical icosahedral
Envelope No Yes (HBsAg) Yes Yes (HBsAg) No
Genome ssRNA dsDNA ssRNA ssRNA ssRNA
Transmission Fecal-oral Parenteral, Parenteral, Parenteral, Fecal-oral
sexual sexual sexual
Onset Abrupt Insidious Insidious Abrupt Abrupt
Incubation 15-50 45-160 14-180 15-64 15-50
period
(days)
Severity Mild Occasionally Usually Coinfection Normal
severe subclinical; with HBV patients,
70% chronicity occasionally mild; pregnant
severe; women, severe
superinfection
with
HBV often
severe

3
 Table: Comparative Features of Hepatitis Viruses…
Feature Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Mortality <0.5% 1%-2% 34% High to very Normal
high patients,
1%-2%;
pregnant
women, 20%
Chronicity/carrier No Yes Yes Yes No
State
Other disease None Primary Primary Cirrhosis, None
Associations hepatocellular hepatocellular fulminant
carcinoma, carcinoma, hepatitis
cirrhosis cirrhosis
Laboratory Symptoms and Symptoms and Symptoms and Anti-HDV -
Diagnosis anti-HAV IgM serum anti-HCV ELISA ELISA
levels of
HBsAg,
HBeAg, and
anti-HBc
IgM

4
 Hepatitis A Virus
• HAV causes infectious hepatitis and is spread by the fecal-oral
route.
• infections often result from consumption of contaminated
water, shellfish, or other food.
• HAV has a 27-nm, naked, icosahedral capsid surrounding a
+ssRNA genome
• There is only one serotype of HAV.

5
Figure: Spread of hepatitis A virus within the body.

6
 Hepatitis A Virus…
• HAV is ingested and probably enters the bloodstream through
the oropharynx or the epithelial lining of the intestines to
reach its target, the parenchymal cells of the liver.
• The virus replicates in hepatocytes and Kupffer cells.
• Virus is produced in these cells and is released into the bile
and from there into the stool.
• Virus is shed in large quantity into the stool approximately 10
days before symptoms of jaundice appear or antibody can be
detected.

7
 Clinical Syndromes
• The symptoms caused by HAV are very similar to those caused by HBV and
stem from immune-mediated damage to the liver.
• Disease in children is generally milder than that in adults and is usually
asymptomatic.
• The symptoms occur abruptly 15 to 50 days after exposure and intensify
for 4 to 6 days before the icteric (jaundice) phase.
• Initial symptoms include fever, fatigue, nausea, loss of appetite, and
abdominal pain.
• Dark urine (bilirubinuria), pale stool, and then jaundice may be
accompanied by abdominal pain and itch.
• Fulminant hepatitis in HAV infection occurs in one to three persons per
1000 and is associated with an 80% mortality rate.
• Unlike HBV, immune complex-related symptoms (e.g., arthritis, rash) rarely
occur in people with HAV disease.
8
Figure: Time course of hepatitis A virus (HAV) infection.

9
Figure. Yellow skin and eyes characterize jaundice.
10
 Laboratory Diagnosis
• The best way to demonstrate an acute HAV infection
is by finding anti-HAV IgM, as measured by an ELISA
or radioimmunoassay.
• Virus isolation is not performed, because efficient
tissue culture systems for growing the virus are not
available.

11
 Treatment, Prevention, and Control
• The spread of HAV is reduced by interrupting the fecal-oral
spread of the virus.
• This is accomplished by avoiding potentially contaminated
water or food, especially uncooked shellfish.
• Prophylaxis with immune serum globulin given before or
early in the incubation period
• Killed HAV vaccines
• A live HAV vaccine has been developed in China

12
 Hepatitis B Virus
• HBV is the major member of the hepadnaviruses.
• These viruses have limited tissue tropisms and host ranges.
• HBV infects the liver and to a lesser extent the kidneys and
pancreas of only humans and chimpanzees.
• HBV is a small, enveloped DNA virus with several unusual
properties
• the genome is a small, circular, partly double-stranded
DNA
• Although a DNA virus, it encodes a reverse transcriptase
and replicates through an RNA intermediate.

13
 Unique Features of Hepadnaviruses

• Virus has enveloped virion containing partially double-

stranded, circular DNA genome.
• Replication is through a circular RNA intermediate.
• Virus encodes and carries a reverse transcriptase.
• Virus encodes several proteins (HBsAg [L, M, S]; HBe/HBc)
• HBV has a strict tissue tropism to the liver.
• HBV-infected cells produce and release large amounts of
HBsAg particles lacking DNA.
• The HBV genome can integrate into the host
chromosome.

14
Figure: Hepatitis B virus (Dane particle) and hepatitis B surface antigen
(HBsAg) particles. The spherical HBsAg consists mainly of the S form of HBsAg,
with some M. The fiber HBsAg has S, M, and L forms.
15
 Hepatitis B Virus…
• HBV can cause acute or chronic, symptomatic or
asymptomatic disease.
• Which of these occurs seems to be determined by the
person's immune response to the infection
• Detection of both the HBsAg and the HBeAg components of
the virion in the blood indicates the existence of an ongoing
active infection.
• The major source of infectious virus is blood, but HBV can be
found in semen, saliva, milk, vaginal and menstrual
secretions, and amniotic fluid.

16
Figure: Major determinants of acute
and chronic HBV infection. HBV infects
the liver but does not cause direct
cytopathology. Cell-mediated immune
lysis of infected cells produces the
symptoms and resolves the infection.
Insufficient immunity can lead to
chronic disease. Chronic HBV disease
predisposes a person to more serious
outcomes.
Purple arrows indicate symptoms; green
arrows indicate a possible outcome.
17
 High-Risk Groups for Hepatitis B Virus Infection

• People from endemic regions (i.e., China, parts of Africa, Alaska,

Pacific Islands)
• Babies of mothers with chronic hepatitis B virus
• Intravenous drug abusers
• People with multiple sex partners, homosexual and heterosexual
• Hemophiliacs and other patients requiring blood and blood
product treatments
• Health care personnel who have contact with blood
• Residents and staff members of institutions for the mentally
retarded
• Hemodialysis patients and blood and organ recipients

18
 Clinical Syndromes
Acute Infection
• Symptoms during the prodromal period may include fever,
malaise, and anorexia, followed by nausea, vomiting,
abdominal discomfort, and chills.
• The classic icteric symptoms of liver damage (e.g., jaundice,
dark urine, pale stools) follow soon thereafter.
• Recovery is indicated by a decline in the fever and renewed
appetite.
• Fulminant hepatitis occurs in approximately 1% of icteric
patients and may be fatal.
• It is marked by more severe symptoms and indications of
severe liver damage, such as ascites and bleeding.
19
 Clinical Syndromes…
• HBV infection can promote hypersensitivity reactions that are
caused by immune complexes of HBsAg and antibody.
• These may produce rash, polyarthritis, fever, acute
necrotizing vasculitis, and glomerulonephritis.

20
Figure: Symptoms of typical acute viral hepatitis B infection are correlated with the four
clinical periods of this disease. RUQ, right upper quadrant. 21
Figure: Clinical outcomes of acute hepatitis B infection.

22
 Clinical Syndromes…
Chronic Infection
• Chronic hepatitis occurs in 5% to 10% of people with HBV
infections, usually after mild or inapparent initial disease.
• Approximately one third of these people have chronic active
hepatitis with continued destruction of the liver leading to
scarring of the liver, cirrhosis, liver failure, or PHC.
• The other two thirds have chronic passive hepatitis and are
less likely to have problems.
• Chronically infected people are at risk for fulminant disease if
they become coinfected with HDV.

23
 Clinical Syndromes…
Primary Hepatocellular Carcinoma
• 80% of all cases of PHC can be attributed to chronic HBV
infections.
• The HBV genome is integrated into these PHC cells, and the
cells express HBV antigens.
• PHC is usually fatal and is one of the three most common
causes of cancer mortality in the world.
• HBV may induce PHC by promoting continued liver repair and
cell growth in response to tissue damage or by integrating into
the host chromosome and stimulating cell growth directly.
• The latency period between HBV infection and PHC may be as
short as 9 years or as long as 35 years.
24
 Laboratory Diagnosis
• The initial diagnosis of hepatitis can be made on the basis of
the
• clinical symptoms and the
• presence of liver enzymes in the blood
• The serology of HBV infection describes the course and the
nature of the disease
• Acute and chronic HBV infections can be distinguished by the
presence of HBsAg and HBeAg in the serum and the pattern of
antibodies to the individual HBV antigens.

25
 Laboratory Diagnosis…
• HBsAg and HBeAg are secreted into the blood during viral
replication.
• The detection of HBeAg is the best correlate to the presence
of infectious virus.
• A chronic infection can be distinguished by the continued
finding of HBeAg, HBsAg, or both, and a lack of detectable
antibody to these antigens.

26
 Laboratory Diagnosis…
• During the symptomatic phase of infection, detection of
antibodies to HBeAg and HBsAg is obscured because the
antibody is complexed with antigen in the serum.
• The best way to diagnose a recent acute infection, especially
during the period when neither HBsAg nor anti-HBs can be
detected (the window), is to measure IgM anti-HBc.

27
Table: Interpretation of Serologic Markers of Hepatitis B Virus Infection

*Anti-HBc IgM should be present.

†Anti-HBe may be negative after chronic disease.
Note:
• Acute: abrupt onset, short duration, rapidly progressive
28
 HBV serological tests
• Hepatitis B surface antigen (HBsAg): marker of current (acute,
chronic) infection
• Hepatitis B e antigen (HBeAg): marker of active infection (acute,
chronic acute)
• Hepatitis B surface antibody (HBsAb): marker of recovery or
immunity
• Hepatitis e-antibody (HBeAb): marker of inactive virus (generally)
(resolved acute, chronic carrier)
• Hepatitis B core antibody (HBcAb): marker of present (acute, IgM)
or past (resolved acute, IgG) infection
• HBV DNA: measures virus activity (active virus).
Note.
• Acute: acute, resolved acute
• Chronic: chronic carrier, chronic active infection 29
 Treatment, Prevention, and Control
• Although no treatment is available for acute infection,
Hepatitis B immune globulin may be administered within a
week of exposure and to newborn infants of HBsAg-positive
mothers to prevent and ameliorate disease.
• Chronic HBV infection can be treated with
• Lamivudine, adefovir dipivoxil and famciclovir, Interferon-


30
 Treatment, Prevention, and Control…

• Transmission of HBV in blood or blood products has been

greatly reduced by screening donated blood for the presence
of HBsAg and anti-HBc.
• Additional efforts to prevent transmission of HBV consist of
avoiding sex with a carrier of HBV and avoiding the lifestyles
that facilitate spread of the virus.
• Vaccination is recommended for infants, children, and
especially people in high-risk groups

31
 Hepatitis C Virus
• HCV was the major cause of post-transfusion hepatitis before
routine screening of the blood supply for HCV.
• Positive-sense RNA genome, enveloped
• HCV is transmitted primarily in infected blood and sexually
• Intravenous drug abusers, tattoo recipients, transfusion and
organ recipients, and hemophiliacs receiving factors VIII or IX
are at highest risk for infection

32
 Clinical Syndromes
• HCV causes three types of disease
• acute hepatitis with resolution of the infection and
recovery in 15% of cases
• chronic persistent infection with possible progression to
disease much later in life for 70% of infected persons
• severe rapid progression to cirrhosis in 15% of patients.

33
Figure: Outcomes of hepatitis C virus infection.
34
 Laboratory Diagnosis
• ELISA recognition of anti-HCV antibody
• ELISA is used for screening the blood supply from
normal donors
• Detection of the RNA genome.

35
 Treatment, Prevention, and Control
• Recombinant interferon- or pegylated interferon (treated
with polyethylene glycol to enhance its biologic lifetime),
alone or with ribavirin, are the only known treatments for
HCV.
• Treatment with pegylated interferon and ribavirin for
extended periods may yield up to 50% recovery rates.

36
 Hepatitis D Virus
• HDV uses HBV and target cell proteins to replicate and
produce its one protein.
• HBsAg is essential for packaging the virus.
• Circular single-stranded RNA, enveloped
• Similar to HBV, the delta agent is spread in blood, semen, and
vaginal secretions.
• However, it can replicate and cause disease only in people
with active HBV infections.

37
 Hepatitis D Virus…
• Because the two agents are transmitted by the same routes, a
person can be coinfected with HBV and the delta agent.
• A person with chronic HBV can also be superinfected with the
delta agent.
• More rapid, severe progression occurs in HBV carriers
superinfected with HDV than in people coinfected with
HBV and the delta agent, because during coinfection HBV
must first establish its infection before HDV can replicate,
whereas superinfection of an HBV-infected person allows
the delta agent to replicate immediately.

38
Figure: The delta hepatitis virion.
39
Figure: Consequences of delta virus infection. Delta virus requires the
presence of hepatitis B virus (HBV) infection.
Superinfection of a person already infected with HBV (carrier) causes more rapid,
severe progression than coinfection
40
 Clinical Syndromes
• The delta agent increases the severity of HBV infections.
• Fulminant hepatitis is more likely to develop in people
infected with the delta agent than in those infected with the
other hepatitis viruses.
• This very severe form of hepatitis causes altered brain
function (hepatic encephalopathy), extensive jaundice,
and massive hepatic necrosis
• Chronic infection with the delta agent can occur in people
with chronic HBV.

41
 Laboratory Diagnosis
• The presence of the agent can be noted by
detecting the
• RNA genome
• Delta antigen
• Anti-HDV antibodies
• ELISA and radioimmunoassay procedures are available
for detection.

42
 Treatment, Prevention, and Control
• There is no known specific treatment for HDV hepatitis.
• Because the delta agent depends on HBV for replication and
is spread by the same routes,
• prevention of infection with HBV prevents HDV infection.
• Immunization with HBV vaccine protects against subsequent
deltavirus infection.
• If a person has already acquired HBV, delta agent infection
may be prevented by halting illicit intravenous drug use and
avoiding HDV-contaminated blood products.

43
 Hepatitis E Virus
• HEV is predominantly spread by the fecal-oral route,
especially in contaminated water
• The symptoms and course of HEV disease are similar to those
of HAV disease
• it causes only acute disease
• The mortality rate associated with HEV disease is 1% to 2%
• HEV infection is especially serious in pregnant women
(mortality rate of approximately 20%)

44
45
Retroviruses
 Property of Retroviruses
• The retroviruses are classified by the diseases they cause,
tissue tropism and host range, virion morphology, and
genetic complexity.
• 7 subfamilies: Oncovirinae, B, C, D, Lentivirinae,
Spumavirinae, Endogenous viruses
• Subfamily C includes: Human T-lymphotropic virus* (HTLV-1,
HTLV-2, HTLV-5)
• Subfamily Lentivirinae includes: Human immunodeficiency
virus (HIV-1, HIV-2)
• Have slow onset of disease; cause neurologic disorders
and immunosuppression
• Both HIV-1 and HIV-2 cause AIDS, but HIV-1 is found worldwide,
whereasHIV-2 is found primarily in West Africa. 47
 Property of Retroviruses …
• The retroviruses are roughly spherical, enveloped, RNA
viruses with a diameter of 80 to 120 nm.
• The envelope contains viral glycoproteins and is acquired
by budding from the plasma membrane.
• The envelope surrounds a capsid that contains two
identical copies of the positive-strand RNA genome inside
an electron-dense core.
• The virion also contains 10 to 50 copies of the reverse
transcriptase (RNA-dependent DNA polymerase) and
integrase enzymes and
• two cellular transfer RNA (tRNAs).

48
 Property of Retroviruses …
• Virus receptor is the initial determinant of tissue tropism
• Replication proceeds through a DNA intermediate termed the
provirus.
• The provirus integrates randomly into the host
chromosome and becomes a cellular gene.

49
Figure. Cross section of HIV. The enveloped virion contains two identical RNA strands, RNA
polymerase, integrase, and two transfer RNAs (tRNAs) base-paired to the genome within
the protein core. This is surrounded by proteins and a lipid bilayer. The envelope spikes are
the glycoprotein (gp) 120 attachment protein and gp41 fusion protein 50
Table. Retrovirus Genes and Their Function Gene Virus Function

51
 Property of Retroviruses …
• Replication of the human retroviruses e.g., HIV starts with
binding of the viral glycoprotein spikes (trimer of gp120 and
gp41 molecules) to
• the primary receptor, the CD4 protein, and a second receptor, a
7-transmembrane G-protein-coupled chemokine receptor
• The co-receptor is either CCR5, which is expressed on macrophages,
peripheral, and other T cells (macrophages, [M]-tropic) or
• a different chemokine receptor (CXCR4), which is expressed primarily
on T cells (T-tropic)
• Chemokines are small peptides involved in promoting
inflammatory responses and chemotaxis.
• A small percentage of people are resistant to infection
because they have mutations in these co-receptors.
52
Fig . Mechanism of HIV attachment to its receptors on the
host cell.
53
HIV Binding to CD4 and a Chemokine Receptor

Source : ASCP, 2008

54
Human Immunodeficiency Virus
(HIV)
FIGURE. Cross-section of human immunodeficiency virus (HIV). In the interior, two
molecules of viral RNA are shown associated with reverse transcriptase. Surrounding
those structures is a rectangular nucleocapsid composed of p24 proteins.
Note that the viral protease and integrase are also located within the
Nuc leocapsid (in addition to the reverse transcriptase),
56
 Pathogenesis and Immunity
• The major determinant in the pathogenesis and disease
caused by HIV is the virus tropism for CD4-expressing T cells
and macrophages
• HIV-induced immunosuppression (AIDS) results from a
reduction in the number of CD4 T cells, which decimates
the helper and delayed-type hypersensitivity (DTH)
functions of the immune response.

57
 Pathogenesis and Immunity …
• HIV primarily infects CD4 T cells and cells of the macrophage
lineage (e.g., monocytes, macrophages, alveolar macrophages
of the lung, dendritic cells of the skin, and microglial cells of
the brain).
• Virus causes lytic infection of CD4 T cells and persistent low-
level productive infection of macrophage lineage cells.
• Virus causes syncytia formation, with cells expressing large
amounts of CD4 antigen (T cells); subsequent lysis of the cells
occurs.
• Virus alters T-cell and macrophage cell function.
• Virus reduces CD4 T cell numbers and helper-cell
maintenance of CD8 T cell and macrophage function.
• CD8 T cell numbers and macrophage function decrease. 58
 Pathogenesis and Immunity …
• In addition to immunodepression, HIV can also cause
neurologic abnormalities.
• The microglial cell and macrophage are the predominant HIV
infected cell types in the brain.
• Infected monocytes and microglial cells release neurotoxic
substances or chemotactic factors that promote
inflammatory responses and neuronal death in the brain.
• The immunosuppression also puts the individual at risk to
opportunistic infections of the brain.

59
Figure. Pathogenesis of HIV. HIV
causes lytic and latent infection of
CD4 T cells and persistent infection of
cells of the monocyte macrophage
family and disrupts neuron function.
The outcomes of these actions are
immunodeficiency and AIDS
dementia.
DTH, delayed-type hypersensitivity

60
Figure. Time course and stages of HIV disease. A long clinical latency period follows the
initial mononucleosis-like symptoms. Initial infection is with the R5-M-tropic virus, and later
the X4-T-tropic virus arises. The progressive decrease in the number of CD4 T cells, even
during the latency period, allows opportunistic infections to occur. The stages in HIV
disease are defined by the CD4 T-cell levels and occurrence of opportunistic diseases. 61
ARC, AIDS-related complex.
Table. Means of HIV Escape from the Immune System

62
 Epidemiology
• AIDS was first noted in homosexual men in the United States
but has spread in epidemic proportions throughout the
population.
• HIV is thought to be derived from a simian immunodeficiency
virus and is genetically most similar to a chimpanzee virus.
• Enveloped virus is easily inactivated and must be transmitted
in body fluids.
• Disease has a long prodromal period.
• Virus can be shed before development of identifiable
symptoms.
• High risk groups include: Intravenous drug abusers, sexually
active people with many partners (homosexual and
heterosexual), prostitutes, newborns of HIV-positive mothers.63
 Transmission
• The presence of HIV in the blood, semen, and vaginal
secretions of infected people and the long, asymptomatic
period of infection are factors that have promoted the spread
of the disease through sexual contact and exposure to
contaminated blood and blood products
• The fetus and newborn are likely to acquire the virus from an
infected mother.
• HIV is not, however, transmitted by casual contact, touching,
hugging, kissing, coughing, sneezing, insect bites, water, food,
utensils, toilets, swimming pools, or public baths.

64
Table. Transmission of HIV Infection

65
 Clinical Syndromes
• AIDS is one of the most devastating epidemics ever recorded.
• Most HIV-infected people will become symptomatic, and the
overwhelming majority of them will ultimately succumb to the disease
without treatment.
• HIV disease progresses from an asymptomatic nonspecific
disease to profound immunosuppression, referred to as full-blown AIDS.
• The diseases related to AIDS mainly consist of opportunistic
infections, cancers, and the direct effects of HIV on the central
nervous system.
• Although rare, there are cases of long-term survivors.
• Some of these result from infection with HIV strains that lack a
functional nef protein.
• Resistance to the virus correlates with a lack of expression of the
chemokine co-receptor for the virus. 66
 Clinical Syndromes…
• Deterioration of the immune response is indicated by increased
susceptibility to opportunistic pathogens, especially those controlled by
CD4 T cells, activated macrophages, CD8 T cells, and DTH responses (e.g.,
yeasts, herpes and other DNA viruses, or intracellular bacteria).
• The onset of symptoms correlates with a reduction in the
number of CD4 T cells to less than 450/µl and increased levels of virus (as
determined by PCR-related techniques) and protein p24 in the blood.
• Full-blown AIDS occurs when the CD4 T-cell counts are less
than 200/µl (oftentimes to 50/µl or undetectable), and virus
load is greater than 75,000 copies per ml and
• involves the onset of more significant diseases, including
HIV wasting syndrome (weight loss and diarrhea for more
than 1 month) and
67
 Clinical Syndromes…
• the occurrence of indicator diseases such as Kaposi
sarcoma or
• specific opportunistic diseases, especially Pneumocystis
pneumonia, Mycobacterium avium-intracellulare
complex infection, and severe cytomegalovirus disease

• AIDS may be manifested in several different ways, including

lymphadenopathy and fever (AIDS-related complex , ARC),
opportunistic infections, malignancies, and AIDS-related
dementia.

68
 Laboratory Diagnosis
• Tests for HIV infection are performed for one of four reasons:
(Genomics, Serology, Immunologic Studies)
1. To identify those with the infection so that antiviral drug
therapy can be initiated,
2. to identify carriers who may transmit infection to others
(specifically blood or organ donors, pregnant women,
and sex partners),
3. to follow the course of disease and confirm the
diagnosis of AIDS, or
4. to evaluate the efficacy of treatment
• The chronic nature of the disease allows the use of serologic
tests to document HIV infection as supplemented by genomic
detection and quantitation using PCR-related techniques. 69
 Laboratory Diagnosis…
• Unfortunately, serologic tests cannot identify recently
infected people.
• HIV is very difficult to grow in tissue culture, and virus
isolation is not performed.
• Recent infection or late-stage disease are indicated by the
presence of large quantities of viral RNA in blood samples,
the p24 viral antigen, or the reverse transcriptase enzyme.
• Viral RNA (in virions) in blood can be detected by the reverse
transcriptase-polymerase chain reaction (RT-PCR), real-time
PCR, and related methods.
• Blood levels of viral RNA are also useful as a monitor for the
success of antiviral drug therapy.
70
 Table. Laboratory Analysis for HIV Test Purpose

RT-PCR, reverse transcriptase polymerase chain reaction. 71

 HIV RDT testing
• In Ethiopia a tiebreaker algorithm using 3 rapid diagnostic
tests (RDTs) in series is used to diagnose HIV.
• Discordant results between the first 2 RDTs are resolved by
a third ‘tiebreaker’ RDT.
1. KHB (KHB, Shanghai kehua Bioengineering Co Ltd,
China): screening (initial) test
2. STAT-PAK (Chembio Diagnostics, USA): confirmatory test
3. Unigold (Trinity Biotech, Ireland): tiebreaker test

72
 HIV RDT testing…
• kHB:
• Negative: client receives NEGATIVE result
• Positive: use a second test to confirm the result of the first
test
• STAT-PAK:
• Positive: client receives POSITIVE result
• Negative: use a third test to break tie
• Unigold:
• Negative: Client receives NEGATIVE result
• Positive: client receives POSITIVE result

73
 Treatment, Prevention, and Control
• An extensive effort to develop antiviral drugs and vaccines
effective against HIV has been initiated worldwide.
• The anti-HIV drugs approved by the U.S. FDA can be classified
as binding, fusion-penetration, nucleoside analogue reverse
transcriptase inhibitors, non-nucleoside reverse
transcriptase inhibitors, integrase, or protease inhibitors.
• Anti-HIV therapy is currently given as a cocktail of several
antiviral drugs termed highly active antiretroviral treatment
(HAART).
• The use of a mixture of drugs with different mechanisms of action has
less potential to breed resistance.
• Multidrug therapy can reduce blood levels of virus to nearly zero and
reduce morbidity and mortality in many patients with advanced AIDS.
74
 Treatment, Prevention, and Control…
• Therapy should be initiated for individuals showing symptoms
of AIDS, AIDS-defining illnesses, or if CD4 T cells drop below
200 per microliter.
• Therapy may also be considered if viral loads are high
(>100,000), even if CD4 numbers are <350 per microliter.

75
Potential Antiviral Therapies for HIV Infection

76
Potential Antiviral Therapies for HIV Infection…

77
 Emerging and reemerging viral diseases

• SARS
• Avian flu virus
• Hanta viruses
• Nipha
• Ebola

78