Tutorial Report

Hematoimmunology Block

Scenario IV

Created by:

Group14

Arif Satria Putra P 1318011022 Nurulia Astri 1318011123

Audya Pratiwi 1318011026 Prizka Putri 1318011128

Aulian Mediansyah 1318011027 Reffilia Irfa 1318011137

Devi Restina 1318011053 Ridho Pambudi 1318011140

M. Agung Y.P 1318011096 Rika Oktaria 1318011142

Marissa Herani 1318011102 Serafina Subagio 1318011152

Faculty of Medicine

Lampung University

2015
Table of Contents ii

Chapter I Scenario 3

Chapter II Discussion

Step 1 4

Step 2 5

Step 3 6

Step 4 8

Step 5

Step 6

Step 7

Reference

ii
 SCENARIO

Multiple disease intermiten

A 37 years old man, went to the doctor with intermitten cough for 5
months. Beside cough, he had weight loss and chronic diarrhea. Several months
ago, he want to the doctor and diagnosing with lung tuberculosis. After taking the
tuberculosis treatment, he has been never cured from his tbc. He has thrush his
mouth and white plaque on this nail, enlargement of lymph nodes in several parts
of body. By anamnesis, he had drug addiction several years ago and had several
partners for his sexual activity.

3
STEP 1

IDENTIFICATION OF UNFAMILIAR TERMS

There are no unfamiliar terms

4
STEP 2

PROBLEM IDENTIFICATION

1. Diagnoses and working diagnose of the scenario

2. What is the etiology of the disease?
3. What is the pathogenesis of the viral infection?
4. How is the pathophysiology of clinical manifestation happened to the
patient?
5. What is the relation between drug addiction and sexual activity with the
disease?
6. What are laboratory examinations?
7. What are treatments for the disease?

5
STEP 3

BRAINSTORMING

1. Diagnose : immunodeficiency
Working diagnose : tuberculosis, diphtheria, HIV

2. HIV disease is caused by infection with HIV-1 or HIV-2, both of which

cause very similar conditions. They different in transmission and
progression risks.

3. Recent studies have yielded important findings on the pathogenesis of HIV

infection. HIV infection leads to immune dysfunction through CD4+ T-
cell depletion (immunodeficiency) and immune activation
(immunosuppression). In vivo imaging studies of nonhuman primates
indicate that the total body pool of CD4+ T cells may provide more
accurate quantitation of immune depletion in HIV infection than the
peripheral blood CD4+ count. Immune activation appears to be driven by
both a homeostatic response to CD4+ cell depletion and an inflammatory
response to HIV infection. The evidence is mounting that ongoing
inflammation and coagulation account for the increased risk of serious
nonopportunistic events in patients with HIV infection. Studies in long-
term nonprogressors indicate that the HIVspecific immune responses in
these patients are distinguished by clonal expansions of antigen-specific
CD8+ T cells.

The pathogenesis of HIV infection includes depletion of the total body

CD4+ T-cell pool, leading to immunodeficiency. This effect is
accompanied by activation of numerous elements of the immune system,
leading to a functional immunosuppression (ie, reduced function of
remaining CD4+ cells) and a state of inflammation and coagulation that
appears to underlie the increased risk of nonopportunistic complications
observed in patients with HIV infection. Inadequate immune response to

6
 HIV infection allows ongoing viral replication, driving continued immune
activation. Recent investigations have focused on clarifying the
relationship between peripheral blood CD4+ T-cell count and the total
body CD4+ T-cell pool, dissecting the role of immune activation and
inflammation in the expanded spectrum of complications in HIV disease,
and identifying potential correlates of protective immunity to HIV.

4. HIV is a virus that can disrupt a person's immune system, particularly T

cells CD 4. In the early stages, there is no typical clinical symptom
indicating that a person is infected by HIV. Clinical symptoms of the acute
phase of infection are as same as the other microorganisms infections,
such as sore throat, myalgia, fever and rash on the skin. Then, when it
started to the chronic phase, there comes the opportunistic infections, such
as the scenario of patients get symptoms such as tuberculosis. In this case,
TB is an opportunistic infection in HIV. In addition, other opportunistic
infections are chronic diarrhea, so the absorption of carbohydrates, fats,
proteins, vitamins and minerals to be disrupted. If a lot of nutrition
incurred rather than absorbed, it will lead to lack of nutrition in the body.
The consequences of inadequate nutrition is weight loss. White plaques on
the nail in the scenario is the result of malnutrition. In addition, if there are
microorganisms in the body of the lymph nodes will work harder because
there are components of the immune system which can help in killing
microorganisms. Therefore, there was enlargement of lymph in several
parts of the body, which means hiv virus has invaded the systemic flow.

5. Drugs addiction and sexual activity are the risk factor of the viral
deployment

6. ELISA test, Western Blot test, CD4/T-cell count, CD4 Percentage

7. The drugs are often referred to as: antiretrovirals, ARVs, anti-HIV or anti-
AIDS drugs.

7
STEP 4

DETAILED-EXPLANATION OF BRAINSTORMING

1. A condition resulting from a defective immune mechanism; may be

primary (due to a defect in the immune mechanism itself) or secondary
(dependent on another disease process), specific (due to a defect in either
the B-lymphocyte or the T-lymphocyte system, or both) or nonspecific
(due to a defect in one or another component of the nonspecific immune
mechanism: the complement, properdin, or phagocytic system).

2. HIV enters the bloodstream and seeks out T-helper lymphocytes, white
blood cells essential to the functioning of the immune system. One of the
functions of these cells is to regulate the immune response in the event of
attack from disease-causing organisms such as bacteria or viruses. When
the virus infects the T-helper lymphocyte, the cell sends signals to other
cells, which produce antibodies. This T-helper lymphocyte cell may also
be called the T4 or the CD4 cell. Antibodies are produced by the immune
system to help get rid of specific foreign invaders that can cause disease.
Producing antibodies is an essential function of our immune systems. The
body makes a specific antibody for each disease. For example, if we are
exposed to measles virus, the immune system will develop antibodies
specifically designed to attack the measles virus. Polio antibodies fight
poliovirus. When our immune system is working correctly, it protects
against these foreign invaders. HIV infects and destroys the T-helper
lymphocytes and damages their ability to signal for antibody production.

3. Recent studies have yielded important findings on the pathogenesis of HIV

infection. HIV infection leads to immune dysfunction through CD4+ T-
cell depletion (immunodeficiency) and immune activation
(immunosuppression). In vivo imaging studies of nonhuman primates
indicate that the total body pool of CD4+ T cells may provide more
accurate quantitation of immune depletion in HIV infection than the

8
peripheral blood CD4+ count. Immune activation appears to be driven by
both a homeostatic response to CD4+ cell depletion and an inflammatory
response to HIV infection. The evidence is mounting that ongoing
inflammation and coagulation account for the increased risk of serious
nonopportunistic events in patients with HIV infection. Studies in long-
term nonprogressors indicate that the HIVspecific immune responses in
these patients are distinguished by clonal expansions of antigen-specific
CD8+ T cells.

The pathogenesis of HIV infection includes depletion of the total body

CD4+ T-cell pool, leading to immunodeficiency. This effect is
accompanied by activation of numerous elements of the immune system,
leading to a functional immunosuppression (ie, reduced function of
remaining CD4+ cells) and a state of inflammation and coagulation that
appears to underlie the increased risk of nonopportunistic complications
observed in patients with HIV infection. Inadequate immune response to
HIV infection allows ongoing viral replication, driving continued immune
activation. Recent investigations have focused on clarifying the
relationship between peripheral blood CD4+ T-cell count and the total
body CD4+ T-cell pool, dissecting the role of immune activation and
inflammation in the expanded spectrum of complications in HIV disease,
and identifying potential correlates of protective immunity to HIV.

Characterization of Total CD4+ T-Cell Pool: In Vivo Imaging

The correlation between peripheral blood CD4+ counts and the spectrum
of clinical manifestations of HIV disease, from generalized
lymphadenopathy at higher counts to cytomegalovirus retinitis at low
counts, is well defined and has been recognized for many years. More
recently, an association has been shown between peripheral blood CD4+
count and risk of nonopportunistic morbidity and mortality. For example,
the CASCADE (Concerted Action on Seroconversion to AIDS and Death
in Europe) study in treatmentnaive patients and the D:A:D (Data

9
Collection on Adverse Events of Anti-HIV Drugs) study in treatment-
nave and treatment-experienced patients showed progressive increases in
risk of all-cause mortality and nonAIDS-related mortality with
decreasing CD4+ counts. Despite its value, the peripheral blood CD4+
count is recognized as an imperfect marker of HIV disease progression.
Baseline CD4+ counts explain only up to 30% of the variability in the ime
to reach AIDS or death (Mellors et al, JAMA, 2007). In patients who have
undergone plenectomy or have received marrow-suppressive therapies
such as interferon-alpha (IFN-a), the CD4+ percentage is a better marker
of immune competence than CD4+ count. Further, given that only a small
percentage (estimated at 2%) of the total pool of CD4+ cells are present in
the blood at any moment in time, even a small change in the distribution of
cells between the lymphoid tissues and blood could result in a large
change in the peripheral blood CD4+ count. Studies have recently been
undertaken in the nonhuman primate simian immunodeficiency virus
(SIV) model of HIV infection to better understand the relationships
between the peripheral CD4+ count and the total CD4+ cell count in health
and during SIV infection. In part, this interest was spurred by epeated
statements at scientific meetings that approximately 70% of CD4+ cells
are located in the gut. This figure seemed high and was difficult to validate
with published experimental data.
To study the total CD4+ cell pool in nonhuman primates, a series of
imaging studies were performed. A nondepleting humanized monoclonal
antibody that binds to CD4 molecules from humans and rhesus macaques
(CDROKT4A/hlgG4 [OKT4A]) was conjugated with indium 111 (111In)
in a manner similar to that used by Rubin and colleagues in 1996 to study
CD4+ T-cell distribution in mice (Proc Natl Acad Sci USA, 1996).

Semiquantitative in vivo images of CD4+ cell distribution were obtained

using a single-photon emission computed tomography (SPECT) camera
with normalization against liver uptake. Quantitative assessment of in vivo
tissue binding by the labeled antibody was performed by ex vivo analysis

10
of tissue in a gamma counter. Total body imaging of CD4+ T-cell pool in
2 uninfected macaques, using indium 111labelled anti-CD4 antibody.
CD4+ counts: left, 1700 cells/mL; right, 1378 cells/mL. Radioactivity was
normalized against activity in the liver. Macaque injected with 111In-
labeled antibody showed binding of the anti- CD4 antibody to CD4+ cells
in vivo. A 10- to 20-fold increase in antibody binding was observed for
CD4+ ells compared with CD4- cells derived from spleen, axillary lymph
nodes, and mesenteric lymph nodes. Total body imaging of the CD4+ cell
pool in uninfected monkeys with normal CD4+ counts showed that uptake
of the antibody was highest in the lymph nodes, tonsils, spleen, blood pool
of the heart, and liver Figure 1). Studies of animals with SIV or simian-
human immunodeficiency virus (SHIV) infection showed that the intensity
of anti-CD4 antibody staining in lymphoid tissues (spleen, tonsils, lymph
nodes) but not in nonlymphoid tissue (heart, kidney, marrow, testes) was
proportional to the peripheral blood CD4+ count (Figure 2, A). Plots of the
peripheral blood CD4+ counts versus radiotracer retention in lymphoid
tissue showed an exponential relationship (Figure 2, C). Thus, decreases in
peripheral CD4+ count at relatively low counts are correlated with larger
decreases in the total CD4+ cell pool than similar absolute decreases at
higher CD4+ counts. The reduction in the total CD4+ pool is quite large as
the eripheral cell count decreases below 200 cells/L, an observation that
fits well with the dramatic increase in risk of opportunistic conditions as
peripheral cell counts decline and continue to fall below this value. Of
note, the density of CD4+ T cells in intestinal tissue appeared to be low.
The gastrointestinal tract appeared to account for no more of the CD4+
pool than the spleen. Immune Activation T-cell activation can be measured
in several ways.

Proliferation can be assessed using an antibody to measure incorporation

of romodeoxyuridine (BrdU) into the DNA of cells during cell division (S
phase of the cell cycle) and by measuring the reduction of intensity of
staining with fluorescent carboxyfluorescein diacetate succinimidyl ester

11
(CFSE), a dye that stains cell cytoskeleton and thus decreases by 50% with
each cell division. Nonproliferationbased assessments of activation include
measuring expression of cell surface markers such as HLA-DR, CD38,
and programmed death-1 (PD-1) or measurements of intracellular proteins
such as Ki67 and IFN-gamma (IFN-g). Immune activation in HIV
infection includes 2 components: (1) the homeostatic response to CD4+
cell depletion, a compensatory mechanism that may include production of
interleukin- 7 (IL-7); and (2) an inflammatory response that includes both
an HIVspecific immune response and bystander immune activation as a
result of the HIV-specific immune response. In HIV infection, CD4+ cell
activation and CD8+ cell activation are regulated differently, reflecting the
different influences of these 2 forces on CD4+ and CD8+ T cells. In a
study in which T-cell proliferation was measured by BrdU incorporation,
HIV-infected patients were categorized into 4 groups according to viral
load and CD4+ count. The level of CD8+ cell activation was correlated
almost exclusively with viral load (Figure 3).

In contrast, the level of CD4+ cell activation was associated with both
viral load and CD4+ cell depletion. The highest levels of CD4+ and CD8+
activation were in the subset of patients with high viral loads and low
CD4+ counts. The second highest level of CD4+ activation occurred in
patients with low CD4+ counts and low viral loads, whereas the second
highest levels of CD8+ activation were in patients with high viral loads
and high CD4+ counts. The differences in activation of CD4+ and CD8+
cells are also evident from a study in patients with well-controlled viral
loads (plasma HIV RNA levels < 50 copies/mL). As can be seen from
Figure 3 (bottom), the level of CD4+ cell activation (BrdU incorporation)
in HIV-infected individuals decreases as the CD4+ count increases and
eventually becomes indistinguishable from that of HIV-uninfected
subjects (Catalfamo et al, Proc Natl Acad Sci USA, 2008). Conversely,
CD8+ cell activation in the HIV-infected group was always greater than
that in the uninfected group. This persistent increase in CD8+ cell

12
activation likely represents ongoing viral replication, even in patients with
plasma HIV RNA levels below 50 copies/mL. Inflammation as a

Component of HIV Immune Activation Patients with HIV infection are at

increased risk of morbidity and mortality from a variety of
nonopportunistic serious conditions, and it has become increasingly clear
that inflammation contributes to this increased risk. The SMART
(Strategies for Management of Antiretroviral Therapy) trial compared
strategies of drug conservation (intermittent antiretroviral therapy to
maintain CD4+ counts above 250 cells/L) versus continuous viral
suppression with antiretroviral therapy. The goal of this trial was to
determine whether reducing overall antiretroviral drug exposure might
reduce the risk of non AIDS-related complications potentially due to
antiretroviral drugs such as heart disease, stroke, and liver failure. The
study was stopped prematurely when it was found that patients in the drug-
conservation group had a higher risk of nonAIDS-related events than did
those in the continuous-treatment group, with a hazard ratio of 1.7 for all
serious nonAIDS-related events. These findings suggested that the
increased risk of nonAIDS-related events was associated more with HIV
replication than with drug toxicity. A subsequent analysis of biomarkers
from stored samples showed that the risk of all-cause mortality was
statistically significantly greater among patients with higher baseline
levels of high-sensitivity C-reactive protein (adjusted odds ratio [OR], 2.8;
P = .03); interleukin-6 (IL-6) (adjusted OR, 11.8; P < .0001); or the
coagulation marker D-dimer (adjusted OR, 26.5; P < .0001) (Kuller et al,
PLoS Medicine, 2008).

In patients receiving intermittent antiretroviral therapy, increases in D-

dimer levels were statistically significantly associated with the increases in
viral load at 1 month after stopping therapy. These findings indicate that
ongoing inflammation and a procoagulant state may underlie the increased
risk of nonAIDS-related events observed in patients with HIV infection.

13
 The elevation of D-dimer levels may be particularly noteworthy because it
suggests that ongoing coagulation in the context of ongoing inflammation
may lead to small-vessel damage and ultimately to end-organ damage.

4. HIV produces cellular immune deficiency characterized by the depletion

of helper T lymphocytes (CD4+ cells). The loss of CD4+ cells results in the
development of opportunistic infections and neoplastic processes.

Virology of HIV
HIV-1 and HIV-2 are retroviruses in the Retroviridae
family, Lentivirus genus. They are enveloped, diploid, single-stranded,
positive-sense RNA viruses with a DNA intermediate, which is an
integrated viral genome (a provirus) that persists within the host-cell
DNA.
HIV contains 3 species-defining retroviral genes: gag, pol, and env.
The gag gene encodes group-specific antigen; the inner structural proteins.
The pol gene encodes polymerase; it also contains integrase and protease
(the viral enzymes) and is produced as a C-terminal extension of the Gag
protein). The env gene encodes the viral envelopethe outer structural
proteins responsible for cell-type specificity. Glycoprotein 120, the viral-
envelope protein, binds to the host CD4+ molecule.
HIV-1 has 6 additional accessory genes: tat, rev, nef, vif, vpu, and vpr.
HIV-2 does not have vpu but instead has the unique gene vpx. The only
other virus known to contain the vpu gene is simian immunodeficiency
virus in chimpanzees (SIVcpz), which is the simian equivalent of HIV.
Interestingly, chimpanzees with active HIV-1 infection are resistant to
disease.

The accessory proteins of HIV-1 and HIV-2 are involved in viral

replication and may play a role in the disease process. The outer part of the
genome consists of long terminal repeats (LTRs) that contain sequences
necessary for gene transcription and splicing, viral packaging of genomic

14
RNA, and dimerization sequences to ensure that 2 RNA genomes are
packaged. (See the image below.)

Genome layout of human

immunodeficiency virus (HIV)1 and HIV-2.
The dimerization, packaging, and gene-transcription processes are
intimately linked; disruption in one process often subsequently affects
another. The LTRs exist only in the proviral DNA genome; the viral RNA
genome contains only part of each LTR, and the complete LTRs are re-
created during the reverse-transcription process prior to integration into the
host DNA.

The biologic basis for AIDS

The specific details of the disease process that leads to AIDS are not fully
understood despite considerable progress in the virology of HIV and the
immunology of the human host, much of which has been driven by the
urge to better understand AIDS.

There is a specific decline in the CD4+ helper T cells, resulting in

inversion of the normal CD4/CD8 T-cell ratio and dysregulation of B-cell
antibody production. Immune responses to certain antigens begin to
decline, and the host fails to adequately respond to opportunistic infections
and normally harmless commensal organisms. Because the defect
preferentially affects cellular immunity, the infections tend to be
nonbacterial (fungal, viral).
The pattern of opportunistic infections in a geographic region reflects the
pathogens that are common in that area. For example, persons with AIDS
in the United States tend to present with commensal organisms such
as Pneumocystis andCandida species, homosexual men are more likely to

15
develop Kaposi sarcoma because of co-infection with HHV8,
and tuberculosis is common in developing countries.

Gut-associated lymphoid tissue (GALT) plays a role in HIV replication.

Although the portal of entry for HIV infection is typically through direct
blood inoculation or exposure of the virus to genital mucosal surfaces, the
GI tract contains a large amount of lymphoid tissue, making this an ideal
site for HIV replication.
GALT has been shown to be a site of early viral seeding and establishment
of the proviral reservoir. This reservoir contributes to the difficulty of
controlling the infection, and efforts to reduce the levels of HIV provirus
through sustained antiretroviral therapy (alone or in combination with
interleukin-2 activation of resting HIV-infected T cells) have consistently
failed.
A feature of HIV replication in GALT is that it is compartmentalized, even
among different areas of the gut. Measurements of CD4+ T cells in GALT
show relatively less reconstitution with antiretroviral therapy than that
observed in peripheral blood. At least one report has suggested that early
treatment may result in better GALT CD4+ T-cell recovery, but clinical
data generally argue against early initiation of therapy, which has not been
shown to improve long-term survival.

In addition, HIV replication can be detected even in patients with

supposedly suppressed replication, as judged by plasma viral load
measurements. CD8+ killer T-cell responses to HIV occur in GALT and do
not decline with antiviral therapy as much as peripheral measurements
do. These findings underscore the limitations of peripheral measurements
in what is really a central viral replication.
One theory for the discrepancy between GALT and blood measurements is
that ongoing viral replication in the lymphoid tissue, and the resulting
immune activation, may actually hamper efficient CD4+ T-cell
replenishment.

16
Studies of T-cellreplication kinetics have revealed that untreated HIV
infection is characterized by rapid T-cell turnover but a defect in T-cell
replication from the thymus. These changes can be reversed with effective
long-term antiviral therapy, suggesting that they are due to a direct effect
of the virus or are a feature of the immune response against HIV.
It is known that normal cell cycling is necessary to produce a normal
cytokine profile and that HIV causes cell-cycle arrest. Whether this is the
exact mechanism is unresolved, however. Analysis of cytokine levels in
HIV infected, uninfected, and HAART-treated patients with HIV show
that cytokines involved in T-cell homeostasis were definitely affected, and
therapy partially corrected these defects. In particular there was decreased
IL-7, IL-12, IL-15 and FGF-2, and increased TNF-alpha and IP-10.

Several of the HIV proteins directly affect T-cell function, either by

disrupting cell cycling or down-regulating the CD4 molecule. The loss of
T cells is clearly a primary issue, as the T-cell repertoire narrows in terms
of which antigens the immune system will recognize and respond to.
Antiviral therapy is able to reverse these changes, but the degree of
reversal is decreased if therapy is initiated very late in the infection and is
further decreased when therapy is initiated when CD4 T-cell counts are
200/L and below.
Direct cytotoxic effects of viral replication are likely not the primary cause
of CD4 T-cell loss; a significant bystander effectis likely secondary to T-
cell apoptosis as part of immune hyperactivation in response to the chronic
infection. Infected cells may also be affected by the immune attack.

One interesting issue is that the co-receptor usage of the virus strains tends
to change over time. The initial infection nearly always involves a strain
that uses the chemokine receptor 5 (CCR5), which is found on
macrophages and dendritic cells, as a co-receptor with CD4. People who
are homozygous for deletions in the CCR5gene (ie, CCR5-delta32) tend to

17
be resistant to infection, and those with heterozygosity for the
polymorphism tend to show slower progression of disease.

Over time, the receptor usage shifts to chemokine-related receptor

(CXCR4) and other related receptors found on CD4+ T cells. These virus
strains are more likely to cause cell fusion (syncytia formation). This trend
is far from absolute but does correlate in many people with disease
progression.
A single case report detailed a possible cure resulting from stem-cell
transplantation from a CCR5-delta32 homozygous donor (performed to
treat acute myelocytic leukemia). Although this important finding is
unlikely to impact routine management of HIV infection, it does suggest
that reconstitution of a host immune system with a population of mutant
cells is a possible avenue of research to explore.
Regardless of the cause for the disruption, a loss of thymic replacements in
the face of an induced state of immune activation and T-cell loss seems to
be a key component of the mechanism by which HIV narrows the T-cell
repertoire and progresses to AIDS.

Visible effects of HIV infection come in the form of disrupted lymph-node

architecture. This disruption is temporal, and, at one point, lymph-node
biopsy was considered as a form of staging the disease. The disruption of
the follicular dendritic network in the lymph nodes and subsequent failure
of normal antigen presentation are likely contributors to the disease
process.
HIV replicates in activated T cells (its promotor contains a nuclear factor
kappa B [NF-kappa-B]binding region, the same protein that promotes
other proteins in activated T cells and macrophages), and activated T cells
migrate to the lymph nodes. As such, much of the viral replication occurs
outside of the peripheral blood, even though serum viral load is still a
useful surrogate marker of viral replication.

18
As mentioned above, with regards to GALT, HIV infection may be
compartmentalized; specifically, areas of immune-privilege may occur
such as in the testes and central nervous system where not only will there
be differences in HIV pseudospecies but also different degrees of
antiretroviral drug penetration. There is evidence that even with good
peripheral control of HIV, the virus may still be detectable in the CSF and
semen of some infected patients.

Phases of HIV infection

Clinical HIV infection undergoes 3 distinct phases: acute seroconversion,
asymptomatic infection, and AIDS. Each is discussed below. (See the
image below.)

Timeline of CD4 T-cell and viral-load

changes over time in untreated human immunodeficiency virus (HIV)
infection. From Wikipedia, based on an original from Pantaleo et al
(1993).

Acute seroconversion
Animal models show that Langerhans cells are the first cellular targets of
HIV, which fuse with CD4+ lymphocytes and spread into deeper tissues. In
humans, rapid occurrence of plasma viremia with widespread
dissemination of the virus is observed 4-11 days after mucosal entrance of
the virus.
There is no fixed site of integration, but the virus tends to integrate in areas
of active transcription, probably because these areas have more open
chromatin and more easily accessible DNA. This greatly complicates
eradication of the virus by the host, as latent proviral genomes can persist
without being detected by the immune system and cannot be targeted by
antivirals. See the image below.

19
 During this phase, the infection is established and a proviral reservoir is
created. This reservoir consists of persistently infected cells, typically
macrophages, and appears to steadily release virus. Some of the viral
release replenishes the reservoir, and some goes on to produce more active
infection.
The proviral reservoir, as measured by DNA polymerase chain reaction
(PCR), seems to be incredibly stable. Although it does decline with
aggressive antiviral therapy, the half-life is such that eradication is not a
viable expectation.
The size of the proviral reservoir correlates to the steady-state viral load
and is inversely correlated to the anti-HIV CD8+ T-cell responses.
Aggressive early treatment of acute infection may lower the proviral load,
but generally, treatment in newly infected (but postseroconversion)
patients yields no long-term benefit.

At this point, the viral load is typically very high, and the CD4+ T-cell
count drops precipitously. With the appearance of anti-HIV antibodies and
CD8+ T-cell responses, the viral load drops to a steady state and the
CD4+ T-cell count returns to levels within the reference range, although
slightly lower than before infection.
Seroconversion may take a few weeks, up to several months. Symptoms
during this time may include fever, flulike illness, lymphadenopathy, and
rash. These manifestations develop in approximately half of all people
infected with HIV.

5. There is a moral and ethical responsibility to address the health needs of

this population upon release from incarceration; however, there are also
important public health benefits to ensuring continued medication
adherence and reduced HIV-transmission risk behaviors. Nearly half of the
respondents reported having unprotected sex, and most of this was with
sero-discordant partners. Also, nearly half of the men had injected drugs in

20
 the period prior to incarceration, and many had shared needles. Post
release planning should include support and skills building for linking to
support for reducing both sexual and IDU-related transmission risk. In
addition, good medical adherence to HIV medication regimens is needed
to keep viral loads low, which considerably lessens the risk of sexual
transmission.

6. Western blot test

Western blotting, also known as immunoblotting or protein blotting, is a
core technique in cell and molecular biology. In most basic terms, it is
used to detect the presence of a specific protein in a complex mixture
extracted from cells. The Western blotting procedure relies upon three key
elements to accomplish this task: the separation of protein mixtures by size
using gel electrophoresis; the efficient transfer of separated proteins to a
solid support; and the specific detection of a target protein by
appropriately matched antibodies. Once detected, the target protein will be
visualized as a band on a blotting membrane, X-ray film, or an imaging
system. Since Western blotting is accomplished rapidly, using simple
equipment and inexpensive reagents, it is one of the most common
laboratory techniques. The results achieved are also easy to interpret,
unique, and unambiguous. Therefore, it is routinely used on its own, or
along with other immunoassays, in research and clinical settings.

Western blots are in wide use across a broad range of scientific and
clinical disciplines. Their ability to clearly show the presence of a specific
protein both by size and through the binding of an antibody makes them
well-suited for evaluating levels of protein expression in cells, and for
monitoring fractions during protein purification . Likewise, they are
helpful for comparing expression of a target protein from various tissues,
or seeing how a particular protein responds to disease or drug treatment. In
many cases, Western blots are used in combination with other key

21
antibody based detection techniques, such as ELISAs or
immunohistochemistry.

ELISA test
Sandwich enzyme-linked immunosorbent assays (ELISAs) involve
attachment of a capture antibody to a solid phase support. Samples
containing known or unknown antigen are then added in a matrix or buffer
that will minimize attachment to the solid phase. An enzyme-labeled
antibody is then added for detection.

The ELISA method is a benchmark for quantitation of pathological

antigens and there are indeed many variations to this method. ELISAs are
adaptable to high-throughput screening because results are rapid,
consistent and relatively easy to analyze. The best results have been
obtained with the sandwich format, utilizing highly purified, prematched
capture and detector antibodies. The resulting signal provides data which
is very sensitive and highly specific. Thus, Invitrogen offers a large menu
of sandwich ELISA and phosphoELISA kits. ELISA and
phosphoELISA kits allow for quantitative measurements of proteins
outside and inside the cell, respectively. For intracellular proteins for
signaling studies, we offer phosphoELISA kits for measurement of total
and phosphorylation, modification, or cleavage sitespecific proteins.

The phosphoELISA kit protocol (Figure 1) begins with a monoclonal

antibody specific for a protein of interest (regardless of phosphorylation
state) coated onto the wells of microtiter strips. Samples, including a
standard containing protein of interest, control specimens, and unknowns,
are pipetted into these wells. During the first incubation, the protein
antigen binds to the immobilized (capture) antibody, much like an
immunoprecipitation. After washing, a rabbit antibody specific for total
protein or protein phosphorylated at a specific residue (e.g., Akt [pS473])
is added to the wells. During the second incubation, this antibody serves as

22
a detection antibody by binding to the immobilized protein captured
during the first incubation. After removal of excess detection antibody, a
horseradish peroxidaselabeled antirabbit IgG antibody (anti-rabbit IgG-
HRP) is added. This binds to the detection antibody to complete the four-
member sandwich. After a third incubation and washing to remove all the
excess anti-rabbit IgG-HRP, a substrate solution is added, which is acted
upon by the bound enzyme to produce color. The intensity of this colored
product is directly proportional to the concentration of total or
phosphorylated protein present in the original specimen. Invitrogen
phosphoELISA kits have been designed to enable the specific detection
of phosphorylation of key signaling molecules, offer great specificity, and
correlate well to western blot data.

The assay procedure for ELISA (Figure 2) and phosphoELISA kits are
similar with only a few minor differences. While the detector antibody for
ELISA kits is biotin-labeled and is followed by incubation with
streptavidin- HRP, the detector antibody for phosphoELISA kits is a
rabbit polyclonal antibody and is followed by incubation with anti-rabbit
IgG-HRP.

23
Figure 1. Schematic of phosphoELISA Figure 2. Schematic of ELISA protocol.
protocol.

CD4 count.
CD4 is a protein that lives on the surface of infection-fighting white blood cells
called T-helper cells. HIV targets these immune cells.
To monitor the health of your immune system, your doctor will check your CD4
count -- the number of CD4 cells in a sample of blood. You should have your
CD4 count tested every three to six months during treatment. Normal CD4 count
is more than 500 cells per cubic millimeter (mm3) of blood. The lower the CD4
count, the less your immune system is functioning, and the more likely you are to
get infections. Your doctor will probably start treatment by the time a CD4 count
is under 500 cells/mm3. If your CD4 count drops to below 200/mm3, you are said
to have full-blown AIDS.

Viral load test. A viral load test measures how much of the HIV virus is in the
blood. You want to have a low viral load because it means treatment is helping to

24
control the virus. If your treatment is working effectively, the viral load should
drop to an undetectable level in your blood.You'll have your viral load tested two
to four weeks after starting treatment, then every four to eight weeks until the viral
load is no longer detectable. An undetectable viral load doesn't mean you're not
infected -- just that the amount of HIV in the blood is too low for the test to pick
up.
Continue to have your viral load tested every three or four months to be sure
antiviral medications are still working.

Drug resistance testing. Your doctor will also test you to make sure the strain of
HIV you have isn't resistant to any medications. Sometimes HIV will change
(mutate) into a form that certain drugs can't treat.

Complete blood count . a blood test that measures white and red blood cell
count, hemoglobin, platelet count, and other components of your blood to check
for anemia and other blood-related conditions

Blood chemistry tests. used to measure the levels of certain substances in the
blood, such as sodium, potassium, creatinine, blood urea nitrogen, and albumin, to
determine how well certain parts of the body are functioning

Urine tests. urinalysis and other urine tests done to check for kidney function and
infections

7. This is the main type of treatment for HIV or AIDS. It is not a cure, but it
can stop people from becoming ill for many years. The treatment consists
of drugs that have to be taken every day for the rest of a persons life.

The aim of antiretroviral treatment is to keep the amount of HIV in the body at a
low level. This stops any weakening of the immune system and allows it to
recover from any damage that HIV might have caused already.

25
The drugs are often referred to as: antiretrovirals, ARVs, anti-HIV or anti-AIDS
drugs.

What is combination therapy?

Taking two or more antiretroviral drugs at a time is called combination therapy.

Taking a combination of three or more anti-HIV drugs is sometimes referred to as
Highly Active Antiretroviral Therapy (HAART).

If only one drug was taken, HIV would quickly become resistant to it and the drug
would stop working. Taking two or more antiretrovirals at the same time vastly
reduces the rate at which resistance would develop, making treatment more
effective in the long term. Our starting, monitoring and switching HIV treatment
page has more about drug resistance.

What does combination therapy usually consist of?

The leading recommendations for antiretroviral treatment were published by the

World Health Organisation (WHO) in 2013. 1 For adults and adolescents, they
recommend starting on a first line therapy of two nucleoside reverse-transcriptase
inhibitors (NRTIs) plus a non-nucleoside reverse-transcriptase inhibitor (NNRTI).
The favoured recommendation is a fixed-dose combination (just one pill) of:

TDF - Tenofovir
3TC - Lamivudine or FTC - Emtricitabine
EFV - Efavirenz

Speak to your health care provider about the most suitable available option for
you. See our Treatment for Children page for specific recommendations for
children.

The choice of drugs to take can depend on a number of factors, including the
availability and price of drugs, the number of pills, the side effects of the drugs,
the laboratory monitoring requirements and whether there are co-blister packs or
fixed dose combinations available. Most people living with HIV in the developing

26
world still have very limited access to antiretroviral treatment and often only
receive treatment for the diseases that occur as a result of a weakened immune
system. Such treatment has only short-term benefits because it does not address
the underlying immune deficiency itself.

First and second line therapy

At the beginning of treatment, the combination of drugs that a person is given is

called first line therapy. If after a while HIV becomes resistant to this
combination, or if side effects are particularly bad, then a change to second line
therapy is usually recommended.

Second line therapy recommendations by WHO suggest two NRTIs and a

ritonavir-boosted protease inhibitor (PI).

Our starting, monitoring and switching HIV treatment page has more information
about changing HIV treatment.

How many HIV and AIDS drugs are there?

There are more than 20 approved antiretroviral drugs but not all are licensed or
available in every country. See our drugs table for a comprehensive list of
antiretroviral drugs approved by the American Food and Drug Administration.

The groups of antiretroviral drugs

There are five groups of antiretroviral drugs. Each of these groups attacks HIV in
a different way.

First
Antiretroviral drug approved
Abbreviations How they attack HIV
class to treat
HIV

27
 NRTIs interfere with
NRTIs, the action of an HIV
Nucleoside/Nucleotide
nucleoside protein called reverse
Reverse Transcriptase 1987
analogues, transcriptase, which the
Inhibitors
nukes virus needs to make
new copies of itself.

NNRTIs also stop HIV

NNRTIs,
from replicating within
Non-Nucleoside Reverse non-
1997 cells by inhibiting the
Transcriptase Inhibitors nucleosides,
reverse transcriptase
non-nukes
protein.

PIs inhibit protease,

which is another
Protease Inhibitors PIs 1995 protein involved in the
HIV replication
process.

Fusion or entry
inhibitors prevent HIV
Fusion or Entry
2003 from binding to or
Inhibitors
entering human
immune cells.

Integrase inhibitors
interfere with the
integrase enzyme,
Integrase Inhibitors 2007 which HIV needs to
insert its genetic
material into human
cells.

28
NRTIs and NNRTIs are available in most countries. Fusion/entry inhibitors and
integrase inhibitors are usually only available in resource-rich countries.

Protease inhibitors are generally less suitable for starting treatment in resource-
limited settings due to the cost, number of pills which need to be taken, and the
particular side effects caused by protease drugs.

29
STEP 5

LEARNING OBJECTIVE

1. Normaly imune response

2. Immunopathogenic mechanism of hiv infection
3. Aspek etika tatalaksana perawatan ODHA di Indonesia
4. Treatment of HIV/AIDS
5. Laboratory exam for HIV/AIDS

30
STEP 6

LITERATURE SEARCHING

31
STEP 7

LITERATURE

1. Normally imune response

Microorganisms invade the body from the skin when it is scraped after injury,
e.g., when you fall down, from the mucous membranes of the respiratory tract
when you passed by someone who coughed, and from the alimentary canal when
the food you ate was rotten. If these microorganisms destroy the epithelium or its
surface is damaged due to other reasons, macrophages and dendritic cells
habitually residing between epithelial cells or in connective tissues directly
underneath perceive their invasion and emit danger signal. These cells possess a
group of recognition molecules called Toll-Like Receptor (TLR) and sugar chain-
recognizing molecules called lectins, which transmit danger signals in accordance
with the characteristics of invader molecules. In concrete terms, transmitting
danger signals means secreting proteins referred to as cytokines and chemokines
that are physiologically active even with a minute amount. By secreting
inflammatory cytokines and chemokines, macrophages mobilize neutrophils, the
cells with a strong ability to directly obliterate microorganisms, from the blood to
the tissues. This stimulates the thermoregulatory center to elevate the body
temperature, thereby inducing swelling of the infected sites.
In general, the response up to this point is a part of natural immunity and is
important in the activation itself of biological defense and acquired immunity until
the subsequent processes of acquired immunity are activated in earnest. Dendritic
cells present the constituent proteins of microorganisms to lymphocytes (antigen
presentation: see Column below) to induce their proliferation and activation. At
this point, the lymphocytes are expressing on their surfaces molecules (such as
antibodies) that can recognize the antigens presented by the dendritic cells.
Although these responses occur within one day after the invasion of
microorganisms, it requires at least 2 to 3 days before antigen-specific
lymphocytes proliferate to reach a sufficient number. Some of the activated

32
lymphocytes eventually start producing antibodies that can bind to
microorganism-derived antigens in several days. As a result of the series of
immune response, infection sources are wiped away in an effective manner.

Humoral Immunity and Cellular Immunity

The final mechanisms to eliminate pathogens (bacteria, viruses, parasites, etc.) as
a consequence of the immune response are classified into two broad categories:
humoral immunity (in which antibodies produced by B cells play pivotal roles)
and cellular immunity (T cells play pivotal roles). Antibodies are soluble proteins
secreted into the blood, and are produced by the same genes that produce
receptors that recognize the antigens on the surfaces of lymphocytes. Humoral
immunity and cellular immunity often work cooperatively with each other, with
the former being more crucial to dealing with extracellular parasites such as
parasitic worms, and the latter to intracellular parasites such as viruses and
tubercle bacilli. Antibodies bind to the surfaces of bacteria to facilitate attack by
other immune systems and bind to viruses to inactivate them. In cellular
immunity, there exist cells specialized in certain roles such as attacking other cells
infected with viruses to induce their cell death.
Some of the lymphocytes that participate in the immune response stay alive even
after the end of response. Upon encountering the same antigens again, these cells
are activated instantaneously to exhibit faster and stronger immune responses than
the first time. This is how the mechanism of "memory" in acquired immunity
functions. This is why the same infectious diseases once contracted before will

33
never infect that same individual again, or even if they did, the symptoms are
abated. Vaccines are pathogenic microorganism-derived substances and similar
attenuated pathogens, which are used to induce the first immune response without
actually developing infectious diseases. It is an attempt to elicit strong immune
response during the genuine first infection in order to thwart the development or
exacerbation of the diseases.
Allergies exemplify the cases in which normally unnecessary immune responses
give rise to diseases and are also classified into those stemming from humoral
immunity (e.g., pollinosis) and those from cellular immunity (e.g., contact
dermatitis). With respect to the former, allergic symptoms are manifested in
response to the extracellular release of chemical compounds conducive to allergic
reactions, which is triggered by the binding of antibodies to cells containing a
copious amount of such compounds

2. Immunopathogenic mechanism of hiv infection

Mechanisms of CD4 T-Lymphocyte Dysfunction

In patients with HIV infection, immunosuppression is due to quantitative as well
as functional defects in CD4 T cells. Several of these have been reviewed
previously and will be discussed only briefly here. Other, more recently proposed
mechanisms will be discussed in greater detail.

Single-Cell Killing and Syncytia Formation

In vitro single-cell killing and syncytia formation occur through direct HIV-
mediated cytopathic effects. Single-cell killing may result from the accumulation
of unintegrated viral DNA or from the inhibition of cellular protein synthesis after
HIV infection. The formation of syncytia involves fusion of the cell membrane of
an infected cell with the cell membranes of uninfected CD4 cells, which results in
giant multinucleated cells. A direct relation between the presence of syncytia and
the degree of the cytopathic effect of the virus in individual cells has been
demonstrated in vitro, and HIV isolated during the accelerated phase of infection

34
in vivo has a greater capacity to induce syncytia in vitro. Syncytia have rarely
been seen in vivo, however. In vitro, their formation may be regulated by the
leukocyte adhesion molecule LFA-1 (lymphocyte-function-associated antigen 1)
produced by human CD4 T lymphocytes inoculated with HIV

HIV-Specific Immune Responses

Both humoral and cellular immune responses contribute to antiviral immunity.
The major antiviral effects of antibodies are attributed to their neutralizing
properties. However, antibodies directed against some regions of the envelope of
HIV may have an additional protective function related to their ability to mediate
antibody-dependent cellular cytotoxicity after binding to natural killer cells,
leading to the killing of HIV-infected cells that express viral-envelope proteins on
their surfaces. HIV-specific cytotoxic T lymphocytes may play an important part
in the immune response against HIV, and they have been found in a substantial
percentage of patients with HIV infection. These mechanisms of immunity and
the effector cells involved may have a dual role, however. The first is a protective
role in the initial immune response to HIV infection, at which time these
mechanisms may help to control or even clear the infection. The second is a
pathogenic role during the chronic phase of infection, when the same mechanisms
may be involved in the elimination of HIV-infected cells (i.e., CD4 T cells,
follicular dendritic cells, and macrophages) and may thus contribute to the
progressive deterioration of the immune system.

Autoimmune Mechanisms
Nonpolymorphic determinants of major-histocompatibility-complex (MHC) class
II molecules, particularly HLA-DR and HLA-DQ, share some degree of structural
homology with the gp120 and gp41 proteins of HIV type 1 and antibodies to these
HIV proteins could therefore cross-react with HLA class II molecules. In fact,
antibodies that react with class II molecules have been found in the serum of
patients with HIV infection. These antibodies could prevent interaction between
CD4 and class II molecules expressed on the antigen-presenting cells, thus

35
impairing the cellular interaction required for efficient antigen presentation and
inhibiting antigen-specific functions mediated by helper CD4 T cells
The hypothesis that gp120 functions as an alloepitope is also based on the
homology between HLA-DR and HLA-DQ molecules and this HIV-envelope
glycoprotein. It has been suggested that gp120 bound to the CD4 molecules of T
cells may trigger a long-term allogeneic immune response. Both of these
possibilities, however, need to be substantiated with more convincing
experimental evidence before their role in the pathogenesis of HIV infection can
be determined.

Anergy
Complexes of gp120 antigen and antibody bind to CD4 molecules, and the CD4
cells become refractory to further in vitro stimulation through the activation of
their CD3 molecules. Similarly, in vitro peripheral-blood mononuclear cells
inoculated with HIV no longer respond to stimulation with anti-CD3 antibodies.
These findings led to the hypothesis that a negative signal is delivered to CD4
cells after their component CD4 molecules react with gp120 or gp120-anti-gp120
complexes. In this regard, anti-gp120 antibodies have recently been detected on
CD4 T lymphocytes in patients with AIDS.

Superantigens
Considerable attention has been given to the possibility that a superantigen, either
retrovirally encoded or unrelated to HIV, may play an important part in the
immunopathogenesis of HIV infection. Superantigens are microbial or viral
antigens that are capable of binding to nearly all T cells that have a specific
variable region of the chain of the T-cell antigen receptor. Unlike conventional
antigenic peptides that bind in the groove of the MHC class II molecules, require
interaction with specific variable components (variable , joining , variable ,
diversity , and joining ) of the and chains of the T-cell antigen receptor, and
thus result in the stimulation of only a tiny fraction of T cells, superantigens bind
only to the variable- region of the T-cell antigen receptor. These superantigens
therefore induce massive stimulation and expansion of T cells bearing the specific

36
variable- regions, followed by deletion or anergy. The superantigen hypothesis
regarding HIV infection stems from the observations that endogenous or
exogenous retroviral-encoded superantigens stimulate murine CD4 T cells in vivo,
leading to the anergy or deletion of a substantial percentage of CD4 T cells that
have the specific variable- regions. In line with this hypothesis, there have been
reports that patients with HIV infection have perturbations of T-cell subgroups
bearing certain specific variable- regions. However, rather than cause deletions
of specific subgroups of T cells, it is more likely that superantigens, if present in
HIV infection, serve as potent activators of T cells, rendering them more
susceptible to infection with the virus.

Apoptosis
Programmed cell death, or apoptosis, is a normal mechanism of cell death that
was originally described in the context of the response of immature thymocytes to
cellular activation. It is a mechanism whereby the body eliminates autoreactive
clones of T cells. It has recently been suggested that both qualitative and
quantitative defects in CD4 T cells in patients with HIV infection may be the
result of activation-induced cell death or apoptosis. Since apoptosis can be
induced in mature murine CD4 T cells after cross-linking CD4 molecules to one
another and triggering the T-cell antigen receptor, there has been speculation that
cross-linking of the CD4 molecule by HIV gp120 or gp120-anti-gp120 immune
complexes prepares the cell for the programmed death that occurs when an MHC
class II molecule in complex with an antigen binds to the T-cell antigen receptor.
Thus, the mere activation of a prepared cell by a specific antigen or superantigen
could lead to the death of the cell, without direct infection by HIV. However,
programmed cell death occurs spontaneously in vitro in the absence of an
antigenic stimulus and occurs in CD8 cells. If confirmed, the apoptosis
hypothesis, like the superantigen hypothesis, would help explain the depletion of
CD4 T cells without requiring that each depleted cell be infected with HIV.

37
3. Aspek etika tatalaksana perawatan ODHA di Indonesia

Dalam mengambil keputusan pada pasien dengan dilema etik harus berdasar pada
prinsip-prinsip moral yang berfungsi untuk membuat secara spesifik apakah suatu
tindakan dilarang, diperlukan atau diizinkan dalam situasi tertentu ( John Stone,
1989 ), yang meliputi :

a. Autonomy / Otonomi
Pada prinsip ini perawat ODHA harus menghargai apa yang menjadi keputusan
pasien dan keluarganya tapi ketika pasien menuntut haknya dan keluarganya tidak
setuju maka perawat harus mengutamakan hak penderita tersebut untuk
mendapatkan informasi tentang kondisinya.

b Benefesience / Kemurahan Hati

Prinsip ini mendorong perawat ODHA untuk melakukan sesuatu hal atau tindakan
yang baik dan tidak merugikan penderita. Selain itu, perawat juga tidak boleh
melakukan tindakan maupun menyampaikan kata-kata yang dapat menyakiti
penderita.

c. Justice / Keadilan
Perawat ODHA harus menerapkan prinsip moral adil dalam melayani pasien. Adil
berarti penderita mendapatkan haknya sebagaimana pasien yang lain juga
mendapatkan hak tersebut yaitu memperoleh informasi tentang penyakitnya
secara jelas sesuai dengan konteksnya/kondisinya.

d. Nonmaleficience / Tidak merugikan

Keputusan yang dibuat perawat ODHA tersebut nantinya tidak menimbulkan
kerugian pada penderita baik secara fisik ataupun psikis yang kronis nantinya.

e. Veracity / Kejujuran
Perawat ODHA harus bertindak jujur jangan menutup-nutupi atau membohongi
penderita tentang penyakitnya. Karena hal ini merupakan kewajiban dan tanggung

38
jawab perawat untuk memberikan informasi yang dibutuhkan penderita secara
benar dan jujur sehingga penderita akan merasa dihargai dan dipenuhi haknya.

f. Fedelity / Menepati Janji

Perawat ODHA harus menepati janji yang sudah disepakati dengan penderita
sebelum dilakukan pemeriksaan yang mengatakan bahwa perawat bersedia akan
menginformasikan hasil pemeriksaan kepada penderita jika hasil pemeriksaannya
sudah selesai. Janji tersebut harus tetap dipenuhi walaupun hasilnya pemeriksaan
tidak seperti yang diharapkan karena ini mempengaruhi tingkat kepercayaan
penderita terhadap perawat tersebut nantinya.

g. Confidentiality / Kerahasiaan
Kerahasiaan berpegang teguh dalam prinsip moral etik perawatan ODHA dimana
harus menghargai apa yang menjadi keputusan pasien dengan menjamin
kerahasiaan segala sesuatu yang telah dipercayakan pasien kepadanya kecuali
seijin pasien. Perawat ODHA memiliki komitmen menyeluruh tentang perlunya
mempertahankan privasi dan kerahasiaan pasien. Beberapa hal terkait dengan isu
ini, yang secara fundamental mesti dilakukan dalam penerapan tehnologi dalam
bidang kesehatan dalam merawat pasien adalah :
1. Jaminan kerahasiaan dan jaminan pelayanan dari informasi kesehatan yang
diberikan harus tetap terjaga
2. Pasien yang mendapatkan informasi tentang potensial resiko (seperti
keterbatasan jaminan kerahasiaan informasi, melalui internet atau telepon)
dan keuntungannya
3. Diseminasi data pasien seperti identifikasi pasien (suara, gambar) dapat
dikontrol dengan membuat informed consent (pernyataan persetujuan)
4. Individu yang menyalahgunakan kerahasiaan, keamanan dan peraturan dan
penyalah gunaan informasi dapat dikenakan hukuman/legal aspek.

39
4. Treatment of HIV/AIDS

There's no cure for HIV/AIDS, but a variety of drugs can be used in combination
to control the virus. Each class of anti-HIV drugs blocks the virus in different
ways. It's best to combine at least three drugs from two classes to avoid creating
strains of HIV that are immune to single drugs.

The classes of anti-HIV drugs include:

a. Non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs
disable a protein needed by HIV to make copies of itself. Examples
include efavirenz (Sustiva), etravirine (Intelence) and nevirapine
(Viramune).
b. Nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs are faulty
versions of building blocks that HIV needs to make copies of itself.
Examples include Abacavir (Ziagen), and the combination drugs
emtricitabine and tenofovir (Truvada), and lamivudine and zidovudine
(Combivir).
c. Protease inhibitors (PIs). PIs disable protease, another protein that HIV
needs to make copies of itself. Examples include atazanavir (Reyataz),
darunavir (Prezista), fosamprenavir (Lexiva) and ritonavir (Norvir).
d. Entry or fusion inhibitors. These drugs block HIV's entry into CD4 cells.
Examples include enfuvirtide (Fuzeon) and maraviroc (Selzentry).
e. Integrase inhibitors. Raltegravir (Isentress) works by disabling integrase, a
protein that HIV uses to insert its genetic material into CD4 cells.

Lifestyle and home remedies

Although it's important to receive medical treatment for HIV/AIDS, it's also
essential to take an active role in your own care. The following suggestions may
help you stay healthy longer:
Eat healthy foods. Emphasize fresh fruits and vegetables, whole grains and
lean protein. Healthy foods help keep you strong, give you more energy
and support your immune system.

40
 Avoid certain foods. Foodborne illnesses can be especially severe in
people who are infected with HIV. Avoid unpasteurized dairy products,
raw eggs and raw seafood such as oysters, sushi or sashimi. Cook meat
until it's well-done or until there's no trace of pink color.
Get immunizations. These may prevent infections such as pneumonia and
the flu. Make sure the vaccines don't contain live viruses, which can be
dangerous for people with weakened immune systems.
Take care with companion animals. Some animals may carry parasites that
can cause infections in people who are HIV-positive. Cat feces can cause
toxoplasmosis, reptiles can carry salmonella, and birds can carry the
fungus cryptococcus or histoplasmosis.

5. Laboratory exam for HIV/AIDS

What follows are descriptions of the most common tests:

a. CD4 count
The CD4 count is like a snapshot of how well your immune system is
functioning. CD4 cells (also known as CD4+ T cells) are white blood cells
that fight infection. The more you have, the better. These are the cells that
HIV kills. As HIV infection progresses, the number of these cells declines.
When the CD4 count drops below 200 due to advanced HIV disease, a
person is diagnosed with AIDS. A normal range for CD4 cells is about
600-1,500. Usually, when a person with low CD4 cells starts HIV
medicines, the CD4 cell count increases as the HIV virus is controlled.
Most but not all people will experience an increase in CD4 cell with
effective HIV treatment.
b. HIV viral load (or 'HIV RNA')
HIV viral load tests measure the amount of HIV in the blood. Lower levels
are better than higher levels. The main goal of HIV drugs is to reduce viral
load as much as possible for as long as possible; for most patients, the goal

41
is to suppress HIV viral load to an "undetectable" level, meaning that the
HIV RNA is below the detection limit of the test.
The lower limit of HIV RNA detection depends on the test used, some go
down to 75 copies/ml, while other go as low as 20. High levels are linked
to faster disease progression. Unlike many other infections for which
treatment can lead to a cure, treatment for HIV suppresses but does not
eliminate the virus. Even if HIV levels are undetectable, the HIV is still in
the body and will rebound to detectable if the HIV medicines are stopped.

42
BIBLIOGRAPHY

Anthony S. Fauci. 2008. Harrison's Internal Medicine, 17th

Edition. USA: McGraw Hill.

A.V. Hoffbrand, J.E. Petit, P.A.H. Moss. 2005. Kapita Selekta

Hematologi Edisi 4. Jakarta: Penerbit Buku Kedokteran EGC.

Guyton & Hall. 2008. Fisiologi Kedokteran Edisi 9. Jakarta : EGC.

Price, A. Sylvia & Lorraine M. Wilson. 2005. Patofisiologi. Jakarta

: EGC.

Sunda Sudoyo, W. Aru, dkk. 2007. Buku Ajar Ilmu Penyakit

Dalam. Jakarta : FK UI.

Giuseppe Pantaleo, Cecilia Graziosi, and Anthony S. Fauci. 1993.

The Immunopathogenesis of Human Immunodeficiency Virus Infection. N
Engl J Med

http://csls-text2.c.u-tokyo.ac.jp/inactive/09_04.html. accessed on
sunday 5 of april 2015 at 12:12pm WIB

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