CHAPTER 1
INTRODUCTION
1.1 Overview
HIV stands for human
immunodeficiency virus. If left untreated, HIV can lead to the disease AIDS
(acquired immune deficiency syndrome).Unlike some other viruses, the human body
can’t get rid of HIV completely. So once one has HIV, they have it for life (AIDS,
HIV and The Immune System, 1997).
HIV is one member of the group of
viruses known as retroviruses. The term "retrovirus" stems from the
fact that these kinds of viruses are capable of copying RNA into DNA. The virus
has two exact copies of single-stranded RNA as its basic genetic material
(genome) in the very center of the organism. The genome is surrounded by a
spherical core made of various proteins in tightlypacked association with one
another. The core is itself surrounded by a membrane (called an "envelope",
made of fat [lipids] and various membrane-bound proteins). One of the
membranebound proteins can bind to a particular protein on the surface of
certain immune cells, called Tcells which results in the virus becoming
physically attached. Upon binding, the virus is brought inside of the T-cell
and the envelope is removed by enzymes normally present inside the cell. The
internal core is thus exposed, and it too is broken-down. This last phase
results in exposure of the virus's RNA genetic material. An enzyme attached to
the RNA, known as "reverse transcriptase", begins to make a
complimentary base-pair single-strand copy of the RNA into DNA. The single
strand of DNA is also copied by the same enzyme to form double-stranded DNA.
This DNA inserts somewhere into one of the 46 chromosomes within our cells, and
there it is used as a template for production of all of the things necessary to
form new virus particles (replication of the virus). These new virus particles
can be subsequently released from the infected cell, and can infect adjacent
cells (AIDS, HIV and The Immune System, 1997).
HIV attacks the body’s immune
system, specifically the CD4 cells (T cells), which help the immune system
fight off infections. If left untreated, HIV reduces the number of CD4 cells (T
cells) in the body, making the person more likely to get infections or
infection-related cancers. Over time, HIV can destroy so many of these cells
that the body can’t fight off infections and disease. Opportunistic infections or cancers take
advantage of a very weak immune system and signal that the person has AIDS, the
last state of HIV infection (AIDS.gov, 2017e).
1.2 HIV strains and types
Each time HIV replicates (by
infecting a new cell), small changes or mutations may occur. This means there
are many different forms of HIV, including within the body of a single person
living with HIV. There are two types of HIV (AVERT, 2017c).
1.2.1 HIV-1 and HIV-2
HIV type 1 and HIV type 2 are two distinct
viruses. Worldwide, the predominant virus is HIV-1.
The relatively uncommon HIV-2
virus is concentrated in West Africa, but has been seen in other countries. It
is less infectious and progresses slower than HIV-1. While commonly used
antiretroviral drugs are active against HIV-2, optimum treatment is poorly
understood (AVERT, 2017c).
The strains of HIV-1 can be classified into
four groups. The most important group, M, is the ‘major’ group and is
responsible for the majority of the global HIV epidemic. The other three groups
are N, O and P. They are quite uncommon and only occur in Cameroon, Gabon and
Equatorial Guinea (AVERT, 2017c).
1.2.3 Subtypes within HIV-1 group M
Within group M there are known to
be at least nine genetically distinct subtypes of HIV-1. These are subtypes A,
B, C, D, F, G, H, J and K. Additionally, different subtypes can combine genetic
material to form a hybrid virus, known as a ‘circulating recombinant form’
(CRFs), of which quite a few have been identified (AVERT, 2017c).
The dominant HIV subtype in the
Americas, Western Europe and Australasia is subtype B. As a result, the great
majority of HIV clinical research has been conducted in populations where
subtype B predominates. However this subtype represents only 12% of global HIV
infections. In contrast, less research is available for subtype C, although
just under half of all people living with HIV have subtype C. It is very common
in the high prevalence countries of Southern Africa, as well as in the horn of
Africa and India (AVERT, 2017c).
The greatest diversity of
subtypes is found in Cameroon and the Democratic Republic of Congo - the region
where the HIV-1 epidemic originated. However, these geographical patterns in
the distribution of subtypes are changing over time, due to migration and the
mixing of populations. Some studies suggest that certain subtypes have a
greater risk of transmission or faster disease progression than others. On the
other hand, antiretroviral drugs (ARVs), although largely developed in relation
to subtype B, have generally proven to be effective against a wide range of
subtypes (AVERT, 2017c).
Nonetheless, comparative research
on these important issues is relatively limited, partly because individuals
with different subtypes are found in distinct geographical locations. A more
practical concern is the tests used to diagnose HIV and monitor the level of
virus in the body (viral load). Tests that are sensitive to the full range of
subtypes (and to group O and HIV-2) do exist but may not be readily available
in all settings. This is a concern in places where diverse subtypes are
prevalent (AVERT, 2017c).
1.3 Acquired immune deficiency syndrome (AIDS)
AIDS stands for acquired
immunodeficiency syndrome. AIDS is the final stage of HIV infection, and not
everyone who has HIV advances to this stage (AIDS.gov, 2017).
AIDS is the stage of infection
that occurs when one’s immune system is badly damaged and one become vulnerable
to opportunistic infections. When the number of CD4 cells falls below 200 cells
per cubic millimeter of blood, patients are considered to have progressed to
AIDS. (The CD4 count of an uninfected adult/adolescent who is generally in good
health ranges from 500 cells/mm3 to 1,600 cells/mm3.) People can also be
diagnosed with AIDS if they develop one or more opportunistic infections,
regardless of their CD4 count (AIDS.gov, 2017).
Without treatment, people who
progress to AIDS typically survive about 3 years. Once patients have a dangerous opportunistic illness,
life-expectancy without treatment falls to about 1 year. However, if they are
taking ART and maintain a low viral load, then they may enjoy a near normal
life span. Patients will most likely never progress to AIDS (AIDS.gov, 2017).
1.4 Opportunistic infections and their relation
to HIV/AIDS
People with healthy immune
systems can be exposed to certain viruses, bacteria, or parasites and have no
reaction to them—but people living with HIV/AIDS can face serious health
threats from what are known as “opportunistic” infections (OIs). These
infections are called “opportunistic” because they take advantage of weakened
immune system, and they can cause devastating illnesses. OIs are signs of a
declining immune system. Most life-threatening OIs occur when CD4 count is
below 200 cells/mm3. OIs are the most common cause of death for people with
HIV/AIDS. The CDC developed a list of more than 20 OIs that are considered
AIDS-defining conditions (AIDS.gov, 2017b).
If people have HIV and one or
more of these OIs, they will be diagnosed with AIDS, no matter what their CD4
count happens to be:
-Candidiasis of bronchi, trachea,
esophagus, or lungs
-Invasive cervical cancer
-Coccidioidomycosis
-Cryptococcosis
-Cryptosporidiosis, chronic
intestinal
-Cytomegalovirus disease (particularly CMV
retinitis)
-Encephalopathy, HIV-related
-Herpes simplex: chronic ulcer(s)
(greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis
-Histoplasmosis
-Isosporiasis, chronic intestinal (greater
than 1 month's duration)
-Kaposi's sarcoma
-Lymphoma, multiple forms
-Mycobacterium avium complex
-Tuberculosis
-Pneumocystis carinii pneumonia
-Pneumonia, recurrent
-Progressive multifocal
leukoencephalopathy
-Salmonella septicemia, recurrent
-Toxoplasmosis of brain
-Wasting syndrome due to HIV
Because they can be so dangerous
to patient’s health, it is essential to understand the signs, symptoms,
prevention, and management of OIs (AIDS.gov, 2017b).
1.5 Origin of HIV AND AIDS
Scientists identified a type of
chimpanzee in Central Africa as the source of HIV infection in humans. They
believe that the chimpanzee version of the immunodeficiency virus (called
simian immunodeficiency virus, or SIV) most likely was transmitted to humans
and mutated into HIV when humans hunted these chimpanzees for meat and came
into contact with their infected blood (CDC.gov, 2017a).
HIV is a type of lentivirus,
which means it attacks the immune system. In a similar way, the SIV virus
(simian immunodeficiency virus) attacks the immune systems of monkeys and apes
(AVERT, 2017b).
Studies show that HIV may have jumped from
apes to humans as far back as the late 1800s. Over decades, the virus slowly
spread across Africa and later into other parts of the world. The virus has
existed in the United States since at least the mid to late 1970s (CDC.gov,
2017a).
1.5.1 Crossing of HIV from chimps to humans
The most commonly accepted theory
is that of the 'hunter'. In this scenario, SIVcpz was transferred to humans as
a result of chimps being killed and eaten, or their blood getting into cuts or
wounds on the human hunter. Normally, the hunter's body would have fought off
SIV, but on a few occasions it adapted itself within its new human host and
became HIV-1 (AVERT, 2017b).
There are four main groups of HIV
strains (M, N O and P), each with a slightly different genetic make-up. This
supports the hunter theory because every time SIV passed from a chimpanzee to a
human, it would have developed in a slightly different way within the human
body, and produced a slightly different strain. This explains why there is more
than one strain of HIV-1 (AVERT, 2017b).
1.5.2 Ways of HIV-2 get passed to humans
HIV-2 comes from SIV in sooty
mangabey monkeys rather than chimpanzees. The crossover to humans is believed
to have happened in a similar way (through the butchering and consumption of
monkey meat). It is far rarer, and less infectious than HIV-1. As a result, it
infects far fewer people, and is mainly found in a few countries in West Africa
like Mali, Mauritania, Nigeria and Sierra Leone (AVERT, 2017b).
1.6 HIV and the Immune System
One of the proteins that envelope
HIV named gp 120, (a sugar-containing protein called a glycoprotein)
“recognizes" a protein on helper T-cells named CD4, and physically
associates with it. The CD4 protein is a normal part of a helper (both Th1 and
Th2) T-cell's membrane. Thus, CD4 is a specific receptor for HIV. This virus
however, can also infect other cells which include macrophages and certain
other kinds of cells which can engulf substances through a process known as
phagocytosis. As a consequence of the interaction with CD4 on helper T-cells,
HIV specifically infects the very cells necessary to activate both B-cell and
cytotoxic T-cell immune responses. Without helper T-cells, the body cannot make
antibodies properly, nor can infected cells containing HIV (an intracellular
pathogen) be properly eliminated. Consequently, the virus can multiply, kill
the helper T-cell in which it lives, infect adjacent helper T-cells, repeat the
cycle, and on and on, until eventually there is a substantial loss of helper
T-cells ( AIDS, HIV and The Immune System, 2017).
The fight between the virus and
the immune system for supremacy is continuous. Our body responds to this
onslaught through production of more T-cells, some of which mature to become
helper T-cells. The virus eventually infects these targets and eliminates them,
too. More T-cells are produced; these too become infected, and are killed by
the virus. This fight may continue for up to ten years before the body
eventually dies, apparently because of the inability to any-longer produce
T-cells. This loss of helper T-cells finally results in the complete inability
of our body to ward-off even the weakest of organisms (all kinds of bacteria
and viruses other than HIV) which are normally not ever a problem to us. This
acquired condition of immunodeficiency is called, AIDS (AIDS, HIV and The
Immune System, 2017).
1.7 The HIV Life Cycle
Binding and Fusion: HIV begins its life cycle when it binds to a
CD4 receptor and one of two coreceptors on the surface of a CD4+ Lymphocyte.
The virus then fuses with the host cell. After fusion, the virus releases RNA,
its genetic material, into the host cell.
(AIDSinfo,2017)
Reverse
Transcription: An HIV enzyme called reverse transcriptase converts the
single stranded
HIV RNA to
double-stranded HIV DNA. (AIDSinfo,2017)
Integration: The
newly formed HIV DNA enters the host cell's nucleus, where an HIV enzyme called
integrates "hides" the HIV DNA within the host cell's own DNA. The
integrated HIV DNA is called provirus. The provirus may remain inactive for
several years, producing few or no new copies of HIV (AIDSinfo, 2017).
Transcription: When the host cell receives a signal to become
active, the provirus uses a host enzyme called RNA polymerase to create copies
of the HIV genomic material. Transcription of the viral genes env, gag and pol
takes place to produce viral RNA, some of which will be incorporated into new
virions and the rest is used in translation to produce three large,
nonfunctional polyproteins, one derived from env, one from gag and the other
from gag-pol gene (Virology Journal, 2017).
Assembly: An HIV enzyme called protease cuts the first long chains
of HIV proteins into smaller individual proteins and produce viral
glycoproteins (gp120, gp41), which are incorporated into cell membrane. The
remaining two polypeptides remain intact and move to the inner surface membrane
(Virology Journal, 2017).
Budding: The newly assembled virus pushes out ("buds")
from the host cell. During budding, the new virus steals part of the cell's
outer envelope. This envelope, which acts as a covering, is studded with
protein/sugar combinations called HIV glycoproteins. These HIV glycoproteins
are necessary for the virus to bind CD4 and coreceptors. The new copies of HIV
can now move on to infect other cells (AIDSinfo, 2017).
1.8 Stages of HIV
Without treatment, HIV advances in
stages, overwhelming immune system and
getting worse over time. The three stages of HIV infection are: (1) acute HIV
infection, (2) clinical latency, and (3) AIDS (acquired immunodeficiency
syndrome) (AIDS.gov,2017c).
1.8.1 Acute infection stage
Within 2-4 weeks after HIV
infection, many people develop flu-like symptoms, often described as “the worst
flu ever.” Symptoms can include fever, swollen glands, sore throat, rash,
muscle and joint aches and pains, and headache. This is called “acute
retroviral syndrome” (ARS) or “primary HIV infection,” and it’s the body’s
natural response to the HIV infection. During this early period of infection,
large amounts of virus are being produced in the body. The virus uses CD4 count
to replicate and destroys them in the process. Because of this, CD4 cells can
fall rapidly. Eventually the immune response will begin to bring the level of
virus in the body back down to a level called a viral set point, which is a relatively stable
level of virus in the body. At this point, your CD4 count begins to increase,
but it may not return to pre-infection levels. During the acute HIV infection
stage, people are at high risk of transmitting HIV to the sexual or drug using
partners because the levels of HIV in the blood stream are very high
(AIDS.gov,2017c).
1.8.2 Clinical latency stage
After the acute stage of HIV infection, the disease
moves into a stage called the “clinical latency” stage. “Latency” means a
period where a virus is living or developing in a person without producing
symptoms. During this stage, people who are infected with HIV experience no
symptoms, or only mild ones. (This stage is sometimes called “asymptomatic HIV
infection” or “chronic HIV infection” (AIDS.gov, 2017c).
During this stage, the HIV virus continues to
reproduce at very low levels, although it is still active. If patients take
ART, they may live with clinical latency for several decades because treatment
helps keep the virus in check. For people who are not on ART, the clinical
latency stage lasts an average of 10 years, but some people may progress
through this stage faster. People in this symptom-free stage are still able to
transmit HIV to others, even if they are on ART, although ART greatly reduces
the risk of transmission (AIDS.gov, 2017c).
1.9 Mode of Transmission
HIV is not spread easily. Only certain
body fluids from a person who has HIV can transmit HIV.
The body fluids are:
•
Blood
•
Semen (cum)
•
Pre-seminal fluid (pre-cum)
•
Rectal fluids
•
Vaginal fluids
• Breast
milk
These body fluids must come into contact with a
mucous membrane or damaged tissue or be directly injected into the bloodstream
(by a needle or syringe) for transmission to occur. Mucous membranes are found
inside the rectum, vagina, penis, and mouth (AIDS.gov, 2017a).
HIV is spread mainly by
•
Having anal or vaginal sex with someone who has
HIV without using a condom or taking medicines to prevent or treat HIV.
•
Anal sex is the highest-risk sexual behavior.
Vaginal sex is the second highest-risk sexual behavior.
•
Sharing needles or syringes, rinse water, or
other equipment used to prepare injection drugs with someone who has HIV. HIV
can live in a used needle up to 42 days depending on temperature and other
factors (AIDS.gov, 2017a).
Less commonly, HIV may be spread
•
From mother to child during pregnancy, birth, or
breastfeeding. Although the risk can be high if a mother is living with HIV and
not taking medicine.
•
By being stuck with an HIV-contaminated needle
or other sharp object. This is a risk mainly for health care workers (AIDS.gov,
2017a).
In extremely rare cases, HIV has been transmitted by
•
Oral sex—putting the mouth on the penis, vagina
or anus. In general, there is little to no risk of getting HIV from oral sex.
But transmission of HIV, though extremely rare, is theoretically possible if an
HIV-positive man ejaculates in his partner’s mouth during oral sex.
•
Receiving blood transfusions, blood products, or
organ/tissue transplants that are contaminated with HIV. This was more common
in the early years of HIV, but now the risk is extremely small because of
rigorous testing of the blood supply and donated organs and tissues.
•
Eating food that has been pre-chewed by an
HIV-infected person. The contamination occurs when infected blood from a
caregiver’s mouth mixes with food while chewing.
The only known
cases are among infants.
•
Being bitten by a person with HIV. Each of the
very small number of documented cases has involved severe trauma with extensive
tissue damage and the presence of blood. There is no risk of transmission if
the skin is not broken.
•
Contact between broken skin, wounds, or mucous
membranes and HIV-infected blood or blood-contaminated body fluids.
•
Deep, open-mouth kissing if the person with HIV
has sores or bleeding gums and blood from the HIV-positive partner gets into
the bloodstream of the HIV-negative partner. HIV is not spread through saliva
(AIDS.gov, 2017a).
1.10 Symptoms of HIV
The symptoms of HIV vary, depending on the
individual and what stage of the disease people are in; the early stage, the
clinical latency stage, or AIDS (the late stage of HIV infection). Below are
the symptoms that some individuals may experience in these three stages. Not
all individuals will experience these symptoms (AIDS.gov, 2017d).
1.10.1 Early stage of HIV
Some people may experience a flu-like illness within
2-4 weeks after HIV infection. But some people may not feel sick during this
stage.
Flu-like symptoms can include:
-Fever -
Rash
-Night
sweats -Chills
-Muscle
aches -Swollen
lymph nodes
-Sore
throat -Fatigue
-Mouth ulcers
These symptoms can last anywhere
from a few days to several weeks. During this time, HIV infection may not show
up on an HIV test, but people who have it are highly infectious and can spread
the infection to others. Each of these symptoms can be caused by other
illnesses. And some people who have HIV do not show any symptoms at all for 10
years or more (AIDS.gov, 2017d).
1.10.2 Clinical latency stage
After the early stage of HIV infection, the disease
moves into a stage called the clinical latency stage (also called “chronic HIV
infection”). During this stage, HIV is still active but reproduces at very low
levels. People with chronic HIV infection may not have any HIV-related
symptoms, or only mild ones (AIDS.gov, 2017d).
1.10.3 Progression to AIDS: AIDS (acquired immunodeficiency
syndrome) is the late stage of HIV infection. Symptoms can include:
-Rapid weight
loss
-Recurring fever or profuse night sweats
-Extreme and unexplained tiredness
-Prolonged swelling of the lymph glands in
the armpits, groin, or neck
-Diarrhea that lasts for more than a week
-Sores of the mouth, anus, or genitals
-Pneumonia
-Red, brown, pink,
or purplish blotches on or under the skin or inside the mouth, nose, or eyelids
-Memory loss, depression, and other neurologic disorders.
Each of these symptoms can also be related to other
illnesses. So the only way to know for sure if anyone has HIV is to get tested.
Many of the severe symptoms and
illnesses of HIV disease come from the opportunistic infections that occur
because the body’s immune system has been damaged (AIDS.gov, 2017d).
1.11 Tests for HIV
There are three broad types of tests available:
antibody tests, combination or fourth-generation tests, and nucleic acid tests
(NAT). HIV tests may be performed on blood, oral fluid, or urine (CDC,
2017b).
1.11.1 Antibody test
Most HIV tests, including most rapid tests and home
tests, are antibody tests. Antibodies are produced by the immune system when
people exposed to viruses like HIV or bacteria. HIV antibody tests look for
these antibodies to HIV in the blood or oral fluid. In general, antibody tests
that use blood can detect HIV slightly sooner after infection than tests done
with oral fluid (CDC, 2017b).
It can take 3 to 12 weeks (21-84 days) for an
HIV-positive person’s body to make enough antibodies for an antibody test to
detect HIV infection. This is called the window period. Approximately 97% of
people will develop detectable antibodies during this window period. If one
gets a negative HIV antibody test result during the window period, they should
be re-tested 3 months after your possible exposure to HIV (CDC, 2017b).
The OraQuick HIV Test, which involves taking an oral
swab, provides fast results. People have
to swab their mouth for an oral fluid sample and use a kit to test it. Results
are available in 20 minutes. The Home Access HIV-1 Test System is a home
collection kit, which involves pricking the finger to collect a blood sample,
sending the sample by mail to a licensed laboratory, and then calling in for
results as early as the next business day. This test is anonymous. The
manufacturer provides confidential counseling and referral to treatment (CDC,
2017b).
1.11.2 Combination or fourth-generation test
It looks for both HIV antibodies and antigens. If
anyone infected with HIV, an antigen called p24 is produced even before
antibodies develop. Combination screening tests are now recommended for testing
done in labs and are becoming more common in the United States. There is now
rapid combinations test available (CDC, 2017b).
It can take 2 to 6 weeks (13 to 42 days) for a
person’s body to make enough antigens and antibodies for a combination, or
fourth-generation, test to detect HIV. This is called the window period. If
anyone gets a negative combination test result during the window period, they
should be retested 3 months after your possible exposure (CDC, 2017b).
1.11.3 A nucleic acid test (NAT)
It looks for HIV in the blood. It looks for the
virus and not the antibodies to the virus. The test can give either a
positive/negative result or an actual amount of virus present in the blood
(known as a viral load test). This test is very expensive and not routinely
used for screening individuals unless they recently had a high-risk exposure or
a possible exposure with early symptoms of HIV infection (CDC, 2017b).
It can take 7 to 28 days for a NAT to detect HIV.
Nucleic acid testing is usually considered accurate during the early stages of
infection. However, it is best to get an antibody or combination test at the
same time to help the doctor interpret the negative NAT. This is because a
small number of people naturally decrease the amount of virus in their blood
over time, which can lead to an inaccurate negative NAT result. Taking
pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) may also
reduce the accuracy of NAT if people have HIV (CDC, 2017b).
1.12 HIV
treatment
HIV treatment doesn't cure HIV. When successful, it
reduces the amount of the virus (your 'viral load') to very low
('undetectable') levels. that it is not able to cause damage to the immune
system. It's now recommended that everyone diagnosed with HIV starts treatment
straight away regardless of their CD4 count. Once patients start treatment, it
is likely they will be taking it for the rest of their life. Treatment with
anti-HIV drugs is sometimes called combination therapy because people usually
take three different drugs at the same time. It is also known as antiretroviral
therapy, or highly active antiretroviral therapy - HAART for short (Terrence
Higgins Trust, 2017).
1.12.1 Types of HIV treatment
Over 25 anti-HIV drugs are now available, in six 'classes'
of drugs. Each class works against HIV in a particular way. People will take a
combination of drugs – usually three.
The classes of anti-HIV drugs are:
•
Nucleoside reverse transcriptase inhibitors
(NRTIs or ’nukes’).
•
Nucleotide reverse transcriptase inhibitors
(NtRTIs).
•
Non-nucleoside reverse transcriptase inhibitors
(NNRTIs or ‘non-nukes’).
•
Protease inhibitors (PIs).
•
Fusion and entry inhibitors.
•
Integrase inhibitors.
(Terrence Higgins Trust, 2017)
1.12.1.1 Nucleoside/Nucleotide Reverse
Transcriptase Inhibitors (NRTIs)
They work by interrupting the life cycle of HIV as
it tries to copy itself. These drugs also have other actions that prevent HIV
from replicating in the body (Healthline, 2017).
1.12.1.2 Non-nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
These drugs work in the same way as NRTIs. They stop
the virus from replicating itself in your body (Healthline, 2017).
1.12.1.3 Protease inhibitors
They work by
binding to protease. This is a protein that HIV needs to replicate in the body.
When protease can’t do its job, the virus can’t complete the process that makes
new copies. This reduces the number of viruses that can infect more cells
(Healthline, 2017).
1.12.1.4 Entry inhibitors (including fusion
inhibitors)
Entry inhibitors are another class of HIV
medications. HIV needs a host T cell in order to make copies of itself. These
drugs block the virus from entering a host T cell. This prevents the virus from
replicating itself. These drugs also prevent the destruction of targeted cells.
This action helps your immune system work better (Healthline, 2017).
1.12.1.5 Integrase Inhibitors
These stop HIV from making copies of itself by
blocking a key protein that allows the virus to put its DNA into the healthy
cell's DNA. They're also called integrase strand transfer inhibitors (INSTIs)
(Healthline, 2017).
1.1 Table: Classes of drugs with examples
|
Class
|
Drug
|
|
NRTI
|
Abacavir
Efavirenz
Emtriacitabine
Tenofovir disoproxil
fumarate
Lamivudine
Zidovudine
Rilpivirine
Didanosine
Stavudine
(Healthline,2017)
|
|
NNRTI
|
Rilpivirine
Etravirine
Delavirdine
mesylate
Efavirenz
Nevirapine
(Healthline,2017)
|
|
Protease
inhibitor
|
Tipranavir
Indinavir
Atazanavir
Saquinavir
Lopinavir
Fosamprenavir
Ritonavir
Cobicistat
Darunavir
Atazanavir
Nelfinavir
(Healthline,2017)
|
|
Entry
inhibitor
|
Enfuvirtide
ibalizumab, PRO 140,
and others are being tested for approval. (WebMD,2017a)
|
|
Integrase
inhibitor
|
Dolutegravir
Elvitegravir
Raltegravir
(Healthline,2017)
|
1.12.1.6 Chemokine co-receptor antagonists (CCR5
antagonists)
CCR5 antagonists prevent the
spread of HIV. These drugs block infection in one of two molecules found on the
surface of each body cell. Because it only affects one molecule, this drug is
usually used with other medications for full HIV treatment. An example of this
type of drug includes:
Maraviroc (Healthline, 2017).
1.12.1.7 Cytochrome P4503A (CYP3A) inhibitors
CYP3A is an enzyme that protects liver and
gastrointestinal (GI) health. HIV can destroy this enzyme, leading to problems
with your liver and GI tract. CYP3A inhibitors protect these enzymes to keep
you healthy. These drugs affect your liver and come with the risk of jaundice.
This may cause yellowing of your skin and the whites of your eyes. An example
of this type of drug includes: Cobicistat (Tybost) (Healthline, 2017).
1.12.1.8 Immune-based therapies
Because HIV affects your immune system, researchers
are studying ways that drugs can help boost immunity. Certain immune-based
treatments have been successful in some people. Like some protease inhibitors,
these drugs are used off-label for HIV. They are used along with other HIV
medications. An example of an immune-based therapy includes: hydroxychloroquine
sulfate which is a drug approved to treat autoimmune diseases such as lupus and
rheumatoid arthritis (Healthline, 2017).
1.13 Side effects of HIV therapy
There are many potential side effects associated
with antiviral therapies. The most common ones for each class of drug are
summarized in readily available product information. Some specific toxicities
are summarized by class below:
•
Most NRTIs can cause mild nausea and loose
stools. In general, these symptoms resolve
with time.
•
ZidovuZdin has been associated with decreased
production of blood cells by the bone marrow, most often causing anemia, and
occasionally hyperpigmentation (most often of the nails).
•
Stavudine can damage nerves and cause peripheral
neuropathy, a neurological condition with numbness and/or tingling of the feet
and hands, and inflammation of the pancreas (pancreatitis) that causes nausea,
vomiting, and mid/upper abdominal pain.
•
DDI also causes pancreatitis and, to a lesser
extent, peripheral neuropathy. Peripheral neuropathy can become permanent and
painful, and pancreatitis can be life-threatening if therapy is not
discontinued. The drug ddC also is associated with peripheral neuropathy, as
well as oral ulcers.
•
Abacavir Sulfate can cause a hypersensitivity
reaction during the first two to six weeks of therapy in approximately 5% of
individuals. The hypersensitivity reaction most often causes fever and other
symptoms, such as muscle aches, nausea, diarrhea, rash, or cough.
•
Tenofovir Disoproxil Fumarate is generally well
tolerated although there may be rare kidney damage and may have a greater
impact on reducing bone density than other agents.
•
Emtricitabine is also well tolerated except for
the occasional development of hyperpigmentation, most often on the palms and
soles. This hyperpigmentation occurs more frequently in people of color.
•
Although all NRTIs can be associated with lactic
acidosis (a serious condition in which lactic acid accumulates in the blood),
it may occur more often with some drugs, such as d4T. Although this
complication of treatment is rare, it can be severe and life threatening. Early
symptoms of lactic acidosis are nausea, fatigue, and sometimes shortness of
breath. Lactic acidosis needs to be watched for and, if suspected, requires
that therapy be discontinued until symptoms and laboratory test abnormalities
resolve.
•
There has been a great deal of attention given
to the more recently identified problem of "lipodystrophy."
Individuals suffering from this syndrome can be categorized as having
lipohypertrophy (fat accumulation) syndromes, such as the "buffalo
hump" on the back of the neck, breast enlargement, or increased abdominal
girth. The NRTIs appear to be most closely linked to lipoatrophy, in particular
D4T and to a lesser extent
ZDV. In fact, some studies have suggested slow accumulation
of fat in those who modify
the NRTI component of their regimen. Some NRTIs also
have been linked to elevation in lipid (fat) levels in the blood.
•
NNRTIs: the most common side effect associated
with NNRTIs is a rash.
•
Side effects associated with Efavirenz are
mostly dizziness, confusion, fatigue, and vivid dreams. These tend to be most
prominent during the first weeks of therapy and then often decrease in
severity.
•
Fusion inhibitors: the only drug in this class
is T-20. The most common side effects are redness and pain at the site of
injection.
•
CCR5 antagonist: although there were some early
concerns of liver inflammation for drugs in this class.
•
Integrase strand transfer inhibitors: RAL has
not been strongly linked to any specific side effect in clinical trials.
However, there have been some cases of muscle problems and of increasing
depression that needs to be watched for when starting this or any new
medications (WebMD, 2017a).
1.14 Monitoring antiviral therapy
The goals of antiviral therapy are to enhance
immunity and delay or prevent clinical advancement to symptomatic disease
without inducing important side effects or selecting for drug-resistant virus.
Currently, the best marker of a drug's activity is a decrease in the viral
load. Ideally, prior to initiating treatment, the viral load and the CD4 cell
count should be checked and the viral load test then repeated after
approximately four weeks of treatment. If the patient is beginning a regimen
that includes two to three drugs for which the patient's virus does not appear
to be resistant, it is expected that the amount of virus should decrease by at
least a hundredfold during this interval. The ultimate goal is for the viral
load to decrease to undetectable levels which should occur by approximately
12-24 weeks. There are some individuals that despite taking all of their
medications correctly will suppress their viral load to less than 200 copies/mL
but not consistently undetectable levels. It is not completely known how to
optimally manage this situation but many experts would continue to monitor on
current therapy as long as viral load remains below 200 copies/mL. Those who
are not having an appropriate response to therapy need to be questioned to make
sure that they are taking their medications correctly, and if not, why. If the
viral load is not going to undetectable levels and the patient is taking the
medications correctly, then it is likely that there is a resistant virus to
some of the medications. (WebMD. 2017b)
1.15 Risks of missing doses or stopping
antiviral therapy
It is strongly advised that individuals on an
antiviral regimen not miss any doses of their medications. Unfortunately, life
is such that doses often are missed. Reasons for missing doses range from just
forgetting to take the medication, leaving town without the medication, or
because of a medical emergency, such as the need for urgent surgery. For
example, after an appendectomy for acute appendicitis, a patient may not be
able to take oral medication for up to several days. When a dose is missed, the
patient should contact his or her physician without delay to discuss the course
of action. The options in this situation are to take the missed doses
immediately or simply resume the drugs with the next scheduled dose. (WebMD.
2017b)
Although every missed dose increases the chance that
the virus will develop resistance to the drugs, a single missed dose should not
be cause for alarm. On the contrary, it is an opportunity to learn from the
experience and determine why it happened, if it is likely to happen again, and
what can be done to minimize missing future doses. Furthermore, if a patient
cannot resume medication for a limited time, such as in a medical emergency,
there still is no cause for alarm. In this circumstance, the patient should
work with their HIV provider to restart therapy as soon as is feasible.
Stopping antivirals is associated with some risks of developing drug
resistance, and those who wish to stop therapy for any one of a number of
reasons should discuss this with their health-care professional in advance to
establish the best strategy for safely accomplishing this (WebMD. 2017b).
1.16 Treatment for HIV during pregnancy
One of the greatest advances in the management of
HIV infection has been in pregnant women. Prior to antiviral therapy, the risk
of HIV transmission from an infected mother to her newborn was approximately
25%-35%. The first major advance in this area came with studies giving ZDV
after the first trimester of pregnancy, then intravenously during the delivery
process, and then after delivery to the newborn for six weeks. This treatment
showed a reduction in the risk of transmission to less than 10%. Although less
data are available with more potent drug combinations, clinical experience
suggests that the risk of transmission may be reduced to less than 5%. Current
recommendations are to advise HIV-infected pregnant women regarding both the
unknown side effects of antiviral therapy on the fetus and the promising
clinical experience with potent therapy in preventing transmission. In the
final analysis, however, pregnant women with HIV should be treated essentially
the same as nonpregnant women with HIV. Exceptions would be during the first
trimester, where therapy remains controversial, and avoiding certain drugs that
may cause greater concern for fetal toxicity, such as Efavirenz (WebMD. 2017b).
All HIV-infected pregnant women should be managed by
an obstetrician with experience in dealing with HIV-infected women. Maximal
obstetric precautions to minimize transmission of the HIV virus, such as
avoiding scalp monitors and minimizing labor after rupture of the uterine
membranes, should be observed. In addition, the potential use of an elective
Caesarean section (C-section) should be discussed, particularly in those women
without good viral control of their HIV infection where the risk of
transmission may be increased. Breastfeeding should be avoided if alternative
nutrition for the infant is available since HIV transmission can occur by this
route. When breastfeeding is done, it should be in conjunction with
antiretroviral therapy for the mother if at all possible (WebMD. 2017b).
1.17 Prevention
HIV is often spread by people who don't know they have it.
So it's always important to protect ourselves and others by taking these steps:
•
Practice of safer sex: Using a condom every time having sex
(including oral sex) until makes sure that the partners aren't infected with
HIV or other sexually transmitted infection (STI).
•
Not having more than one sex partner at a time.
The safest sex is with one partner who has sex only with one.
•
Talking with partner before having sex for the
first time. Finding out if he or she is at risk for HIV. Get tested together.
Getting tested again at 6, 12, and 24 weeks after the first test can be done to
be sure neither of them are infected. Using condoms in the meantime.
•
Avoid drinking a lot of alcohol or using illegal
drugs before sex. People may let down their guard and not practice safer sex.
•
Not sharing personal items, such as toothbrushes
or razors.
•
Never share needles or syringes with anyone.
•
If anyone is at high risk for getting infected
with HIV, he\ she can take antiretroviral medicine to help protect themselves
from HIV infection. Experts may recommend this for:
Ø
People whose sexual practices put them at high
risk for HIV infection, such as men who have sex with men and people who have
many sex partners.
Ø
People who inject illegal drugs, especially if
they share needles.
Ø
Adults who have a sex partner with HIV.
To keep the risk low, people
still need to practice safer sex even while they are taking the medicine
(WebMD. 2017b).
1.18 Myths of HIV
•
HIV is a death sentence: “With proper treatment,
we now expect people with HIV to live a normal life span,” says Dr. Michael
Horberg, national director of HIV/AIDS for Kaiser Permanente. “Since 1996, with
the advent of highly active, antiretroviral therapy, a person with HIV in an
industrialized nation can expect to live a normal life span, so long as they
take their prescribed medications,” adds Dr. Amesh A. Adalja, a board-certified
infectious disease physician with the University of Pittsburgh.
•
One can tell if someone has HIV/AIDS by looking
at them: Often, there are no visible signs of HIV/AIDS. “Some people develop
HIV symptoms shortly after being infected. For others, it can take up to 10
years for symptoms to appear,” says Dr. Gerald Schochetman, senior director of
infectious diseases with Abbott Diagnostics. Schochetman worked at the CDC
during the height of the AIDS crisis. Further, the first symptoms of HIV,
including a fever, fatigue, and muscle aches, may only last for a few weeks.
“Thus, it’s very hard for people to know if they or someone else has HIV
without being properly tested,” says Schochetman.
•
Straight people don’t have to worry about HIV
infection: “We know that the highest risk group is men who have sex with men,”
says Dr. Horberg. This group accounts for about 78 percent of new infections,
according to the CDC. “However, heterosexuals accounted for 24 percent of new
HIV infections in 2010, and about two-thirds of those were women.”
•
HIV-positive people can’t safely have children:
It is possible to have a child if one and his\her partner is HIV-positive.
While it’s impossible to guarantee that the infection won’t pass on to the
child, the U.S. Department of Health and Human Services says there are ways to
greatly reduce the risk. For example, an HIV-positive woman can take
antiretroviral therapy (ART) before and during pregnancy. “As long as a partner
takes their medication correctly and has an undetectable viral load, the
likelihood of transmitting the infection to their child is pretty slim to
none,” explains psychotherapist Keeley Teemsma, who has specialized in the
treatment of HIV/AIDS patients.
•
HIV always leads to AIDS: HIV is the infection
that causes AIDS. But this doesn’t mean all HIV-positive individuals will
actually develop AIDS. “With current therapies, levels of HIV infection can be
controlled and kept low, maintaining a healthy immune system for a long time
and therefore preventing opportunistic infections and a diagnosis of AIDS,”
explains Dr. Richard Jimenez, professor of public health at Walden University.
•
With all of the modern treatments, HIV is no big
deal: This sort of attitude has led some
to practice carefree and reckless sexual behavior. “The younger generation has
lost some fear of HIV because of the success of treatment,” explains Dr.
Adalja. “This has caused them to engage in risky behaviors, leading to high
rates of infection in young men who have sex with other men.”
•
If I take PrEP, I don’t need to use a
condom: PrEP (pre-exposure prophylaxis)
is a medication that can prevent HIV infection in advance. According to Dr.
Horberg, a recent study from Kaiser Permanente followed people using PrEP for
two and a half years, and found that it was effective at preventing HIV
infections. However, it doesn’t protect against other sexually transmitted
diseases or infections. “Prep is recommended to be used in combination with
safer sex practices, as our study also showed that half of the patients
participating were diagnosed with a sexually transmitted infection after 12
months,” says Dr. Horberg.
•
If one test negative for HIV, he\she can have
unprotected sex: If you or your partner was recently infected with HIV, it may
not show up on an HIV test until about three months later. “Traditionally used
antibody-only tests work by detecting the presence of antibodies in the body
that develop when HIV infects the body,” explains Dr. Schochetman. “But it takes
about three weeks for there to be enough antibodies for detection. “Before you
should even consider having unprotected sex, you should take a second HIV test
three months after the first, to confirm your negative reading. If you are
having regular sex, the San Francisco AIDS Foundation suggests getting tested
every three months. Other tests, known as HIV combo tests, can detect the virus
earlier.
•
If both partners have HIV, there’s no reason for
a condom: Not all strains of HIV are the same, and being infected with more
than one can lead to greater complications, or a “superinfection,” according to
Dr. Schochetman. “The new HIV strain may exhibit a different drug resistance
profile than the original HIV infection,” he explains. “And the new virus may
show resistance to the current treatment, or cause the current treatment option
to be ineffective” (Healthline, 2017).
1.19 Epidemiology
HIV continues to be a major global public health
issue. In 2015, an estimated 36.7 million people were living with HIV
(including 1.8 million children) – a global HIV prevalence of 0.8%.1 2.The vast
majority of this number live in low- and middle- income countries. In the same
year, 1.1 million people died of AIDS-related illnesses.Since the start of the
epidemic, an estimated 78 million people have become infected with HIV and 35
million people have died of AIDS-related illnesses(AVERT,2017a).
In 2015, there were roughly 2.1 million new HIV
infections, 150,000 of which were among children. Most of these children live
in sub-Saharan Africa and were infected via their HIVpositive mothers during
pregnancy, childbirth or breastfeeding (AVERT, 2017a)
Progress in decreasing new HIV infections among
adults has slowed in recent years. Since 2010, the annual number of new
infections among adults (15+) has remained static at 1.9 million (AVERT,
2017a).
A comparison of country data shows huge
discrepancies in efforts to slow the spread of new infections. Some countries
have achieved a decline of 50% or more in new HIV infections among adults over
the last 10 years, while many have made no measurable progress. Yet others are
experiencing worrying increases in new HIV infections (AVERT, 2017a)
In 2015, US$ 19 billion was invested in the HIV and
AIDS response in low- and middle- income countries with 57% of the total HIV
resources in these countries coming from domestic budgets. Rising numbers of
new HIV infections in many countries means that US$ 26.2 billion will be
required for the response to the epidemic in 2020, with US$ 23.9 billion
required in 2030 (AVERT, 2017a).
1.20 Scenario in Bangladesh
Bangladesh remains a low HIV prevalence country with
less than 0.1% overall prevalence in general population over the years. The HIV
prevalence remains less than 1% both among key and bridge populations. Till
date, the country has registered a total of 3674 cases of HIV infection.
However, the estimated number of people living with HIV is around 9500.
Although the prevalence remains low, Bangladesh is one of the only four
countries in Asia and the Pacific where prevalence has increased more than 25%
over a decade till 2012.
•
In 2014 Number of people living with HIV are
8,900 [8,000 - 9,800]
•
Adults aged 15 to 49 prevalence rate <0.1%
[<0.1% - <0.1%]
•
Adults aged 15 and up living with HIV 8,600
[7,700 - 9,400]
•
Women aged 15 and up living with HIV 2,900
[2,600 - 3,100]
•
Children aged 0 to 14 living with HIV <500
[<500 - <500]
•
Deaths due to AIDS <1000 [<1000 - 1,200]
• Orphans
due to AIDS aged 0 to 17 N/A (UNAIDS, 2015).
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