HUMAN IMMUNODEFICIENCY VIRUS

INTRODUCTION

Human Immunodeficiency Virus (HIV) is a type of retrovirus that causes immunosuppression. HIV progresses to
Acquired Immunodeficiency Syndrome (AIDS) when the virus has severely damaged the immune system, and the
body can no longer fight off infections. There currently is no cure for HIV, but medication can help patients live a healthy
life with a normal life expectancy.HIV can be transmitted through sexual intercourse with an infected partner, needle-
sharing, and to an infant during pregnancy, childbirth, or breastfeeding. HIV cannot be transmitted casually through a
handshake, sharing utensils, kissing, or hugging.

There are two types of HIV, HIV-1 and HIV-2, as well as several related viruses that infect certain monkeys or great apes.
HIV-1 can be found throughout the world, but HIV-2 is almost exclusively limited to West Africa. HIV-1 is transmitted more
easily than HIV-2, and HIV-1 infection progresses more rapidly to AIDS.

HIV infects cells of the human immune system, particularly a kind of white blood cell called the CD4 T-cell. These cells
help in identifying and destroying harmful material in the body, including bacteria, viruses, parasites, and even some
cancer cells. Over time, HIV infection destroys the CD4 cells, leading to a weakened immune system, certain kinds of
infections, severe illness, and death. The infections are often called “opportunistic infections” (OIs) because they are rare
or mild in healthy people but can take advantage of the opportunity provided by the HIV-weakened immune system and
can be life threatening. The HIV virus can also damage tissue directly, causing neurologic disease, heart disease, and
other problems.
The CD4 cell count (sometimes called a T-cell count) is a measure of the number of CD4 cells in one microliter of blood.
People with HIV and their health care providers use the CD4 count to monitor the infection over time.

ANATOMY AND PHYSIOLOGY

HIV STRUCTURE

The human immunodeficiency viruses are approximately 100 nm in diameter. It has a lipid envelope, in which are
embedded the trimeric transmembrane glycoprotein gp41 to which the surface glycoprotein gp120 is attached (Box 1.1).
These two viral proteins are responsible for attachment to the host cell and are encoded by the env gene of the viral RNA
genome. Beneath the envelope, is the matrix protein p17, the core proteins p24 and p6 and the nucleocapsid protein p7
(bound to the RNA), all encoded by the viral gag gene. Within the viral core, lies 2 copies of the ~10 kilobase (kb) positive-
sense, viral RNA genome (i.e. it has a diploid RNA genome), together with the protease, integrase and reverse
transcriptase enzymes. These three enzymes are encoded by the viral pol gene. There are several other proteins coded
for by both HIV-1 and HIV-2, with various regulatory or immuno-modulatory functions, including vif (viral infectivity
protein), vpr (viral protein R), tat (transactivator of transcription), rev (regulator of viral protein expression)
and nef (negative regulatory factor). An additional protein found in HIV-1 but not HIV-2 is vpu (viral protein U).
Similarly, vpx (viral protein X) is found in HIV-2 and not HIV-1.
HIV replication

The main attachment receptor for HIV is the CD4 molecule that is present on the CD4 positive T (helper) lymphocyte,
macrophages, and microglial cells. The viral gp120 binds initially to this CD4 molecule, which then triggers a
conformational change in the host-cell envelope that allows binding of the co-receptor (either CCR5 or CXCR4) which is
required for fusion between virus envelope and cell membrane.

Macrophages carry the CCR5 co-receptor, hence HIV strains requiring the CCR5 co-receptor for entry are also referred to
as 'macrophage-tropic' although they also infect lymphocytes.6 These HIV strains are also known, phenotypically, as R5
or non-syncytium inducing (NSI) strains as they do not form syncytia (cell-fusion) when cultured with CD4 lymphocytes in
vitro. Primary HIV-1 infections tend to involve this R5 NSI macrophage-tropic phenotype. Uncommonly, individuals may
have a homozygous deletion mutation in the CCR5 gene (CCR5Δ32) resulting in the absence of the CCR5 molecule on
their macrophages. Therefore, these individuals cannot be infected by this R5 phenotype.1,6,7 The 'lymphotrophic' HIV
strains use CXCR4 as the co-receptor. These viruses are also known as X4 viruses and do produce syncytia (i.e. are
phenotypically syncytium-inducing, SI) when cultured in vitro with CD4 lymphocytes. X4 viruses tend to appear later in
about 50% of HIV-1 subtype B-infected individuals, but seldom with other subtypes, as they progress to AIDS.1 So far,
CXCR4 deficient individuals have not been found. This attachment and fusion process allows the HIV viral core to enter
the host-cell.

All retroviruses encode an reverse transcriptase enzyme that transcribes its viral RNA into double-stranded DNA (dsDNA),
which is then integrated, via the action of the integrase enzyme into the host-cell genome (Box 1.2). The viral integrated
dsDNA or 'provirus' then acts as a template for viral genomic and messenger RNA transcription by the host cell's nucleic
acid replicating machinery. Recombination between these two RNA strands during viral replication, coupled with the
extremely error-prone action of the RT enzyme, give rise to the extreme genetic diversity of HIV.1,6
Integration of the linear provirus dsDNA into the genome of the host-cell establishes an infection that lasts for the lifespan
of the cell, and all its progeny, which usually means life-long infection for the organism, in this case the human host. Viral
replication occurs along with cellular replication and is enhanced by various factors, including coinfection with other
organisms, the presence of inflammatory cytokines and cellular activation. During cellular replication, the provirus is
transcribed by the host-cell RNA polymerase II enzyme, and the viral messenger RNA (vmRNA) and genomic RNA, are
carried with the cellular mRNAs, to be translated into proteins. This vmRNA codes for a gag-pol precursor polypeptide that
is ultimately cleaved by the viral-encoded protease enzyme to produce the gag and pol viral proteins. In addition, the
vmRNA is also spliced to produce other vmRNAs coding for the viral proteins tat, rev, vif, vpr, vpu (for HIV-1), as well as
the env precursor polypeptide. Ultimately, the env precursor polypeptide is cleaved by cellular (not viral) proteases,
producing the envelope glycoproteins gp41 and gp120. These viral proteins, together with the replicated diploid viral
genomic RNA, are assembled and enveloped by budding through the host-cell membrane, producing complete HIV
virions.

ETIOLOGY AND SYMPTOMATOLOGY

ETIOLOGY

PREDISPOSING FACTORS IMPLICATION

Age Most cases are among sexually active people
aged between 20-49 years
Gender Women are disproportionately affected by HIV
compared to men, with young women most at
risk.
Sexual Contact Male to male
Male to female
Female to female
Perinatal Transmission Transmission from mother to baby
Breastfeeding
Hemophilia It is estimated that about 50% of all those with
hemophilia became infected, including around
90% of those with severe hemophilia.
Thousands of people with hemophilia developed
AIDS and died from this disease. Many others
from that era still live with HIV today.

Sexually Transmitted Disease an STD can cause a sore or a break in the skin,
which can make it easier for HIV to enter the
body
PRECIPITATING FACTORS IMPLICATION
Multiple Sex Partners Having unprotected sex with multiple sexual
partners (MSP) is the greatest risk factor for
human immunodeficiency virus (HIV) and other
sexually transmitted infections (STIs)
Drug Abusers People who engage in drug use or high-risk
behaviors associated with drug use put
themselves at risk for contracting or transmitting
viral infections such as human
immunodeficiency virus (HIV), acquired immune
deficiency syndrome (AIDS), or hepatitis.
Blood Exposure Injecting drug use/ sharing
Transfusion of blood products
Sex Workers Female sex workers are 30 times more likely to
have HIV than the general female population. Of
all new HIV infections in 2021, 12% were among
sex workers. Around 33% of sex workers do not
know their HIV status.

SYMPTOMATOLOGY

SYMPTOMS RATIONALE
Fever Fever is usually one of the first symptoms of HIV. When you have a
fever your body temperature increases above a normal range, and often
results in sweating, chills and shivering. Fever is often accompanied by
other mild symptoms, such as fatigue, swollen lymph glands, and a sore
throat. At this point the virus is moving into the blood stream and starting
to replicate in large numbers. As that happens, your immune system
induces an inflammatory reaction.
Fatigue and Headache The inflammatory response generated by your besieged immune
system can cause you to feel tired and lethargic. Sometimes it can
make you feel winded while walking or generally feel out of breath.
Fatigue can be both an early and later symptom of HIV.
Rash Skin rashes can occur early or late in the course of HIV seroconversion
and can last between two and three weeks. The rash may start as
feeling non-itchy, but in some cases, can appear similar to boils with
itchy, pink breakouts.
Sore Throat and Dry A severe, dry cough that can last for weeks to months without seeming
Cough to resolve (even with antibiotics and inhalers) is a typical symptom in
very ill HIV patients. Any person with persistent symptoms such as
these should see a doctor, especially if symptoms are worsening.
Swollen Lymph Nodes Lymph nodes are part of your body’s immune system and protect your
blood by getting rid of bacteria and viruses. They tend to get inflamed
when there’s an infection. Many of them are located in your armpit,
groin and neck which can result in aches and pains in these areas.
Diarrhea Many people experience digestive system problems as a symptom of
the early stages of HIV. However, nausea, vomiting and diarrhea can
also appear in later stages of infection, usually as the result of an
opportunistic infection. It is important to stay hydrated. Diarrhea that is
unremitting and not responding to usual therapy might be an indication
of HIV
Night Sweats Night sweats are repeated episodes of extreme sweating, causing
bedding and any nightclothes to become soaked. Many people will get
night sweats during the early stages of HIV. These can be even more
common later in infection and aren’t related to exercise or the
temperature of the room.
GENERAL PATHOPHYSIOLOGY

MEDICAL MANAGEMENT

The treatment of HIV with medicines is called antiretroviral

therapy (ART). It involves taking a combination of medicines
every day. ART is recommended for everyone who has HIV. The
medicines do not cure HIV infection, but help people with HIV live
longer, healthier lives. They also reduce the risk of spreading the
virus to others.

There are six main types (‘classes’) of antiretroviral drugs.

1. Nucleoside reverse transcriptase inhibitors (NRTIs), and nucleotide reverse transcriptase inhibitors (NtRTIs),
often all referred to as NRTIs, work by targeting the action of an HIV protein called reverse transcriptase.
2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) also target reverse transcriptase, but in a different
way to NRTIs.NNRTIs interfere with the reverse transcriptase enzyme by binding directly to it, blocking the
reverse transcription process.
3. Integrase inhibitors target a protein in HIV called integrase which is essential for viral replication.
4. Entry inhibitors stop HIV from entering human cells. There are two types: CCR5 inhibitors and fusion inhibitors.
5. Protease inhibitors (PIs) block the activity of the protease enzyme, which HIV uses to break up large
polyproteins into the smaller pieces required for assembly of new viral particles. While HIV can still replicate in the
presence of protease inhibitors, the resulting virions are immature and unable to infect new cells.
6. Attachment inhibitors bind to the gp120 portion of the HIV envelope protein that makes up the spikes on the
surface of the virus. This prevents the virus from attaching to the CD4 receptor on T cells and other immune cells,
which it uses to gain entry to the cells. One attachment inhibitor is available.

LABORATORIES

 CD4 T-cell count indicates the current immune status and risk of acquiring an infection. CD4 counts are typically between
500-2000. A CD4 count below 200 is considered AIDS.
 HIV viral load test. It’s a lab test that measures of the amount of HIV in your blood. When your viral load is high,
you have more HIV in your body. This means your immune system is not fighting HIV very well. HIV viral load
tests are used to monitor the progress of your HIV infection and how well your treatment is working. Once you
start HIV medicine, you want your viral load to decrease and stay low.
  Drug Resistance Tests: HIV can change form, making it resistant to some HIV medicines. A drug resistance test
helps your health care provider identify which, if any, HIV medicines will not be effective against the strain of HIV
you have and choose which HIV medicines are most likely to work for you.

MEDICATIONS

TREATMENT

Currently, there's no cure for HIV/AIDS. Once you have the infection, your body can't get rid of it. However, there are
many medications that can control HIV and prevent complications. These medications are called antiretroviral therapy
(ART). Everyone diagnosed with HIV should be started on ART, regardless of their stage of infection or complications.

ART is usually a combination of two or more medications from several different drug classes. This approach has the best
chance of lowering the amount of HIV in the blood. There are many ART options that combine multiple HIV medications
into one pill, taken once daily.

NURSING MANAGEMENT

Administer antiretroviral therapy (ART).

Antiretroviral therapy (ART) is the most effective management of HIV. ART often involves two or more drugs from several
pharmacological classes together.

Encourage treatment adherence.

Patients must strictly adhere to their medication regimen as prescribed. Patients who adhere to their treatment plan can
maintain control of the virus and may never progress to AIDS. When ART is taken as prescribed, the medication provides
the following benefits:
 Boosts the immune system
 Reduces the infection risk
 Lessens the likelihood of treatment-resistant HIV
 Decreases the risk of HIV transmission to others

Ensure the patient’s optimal health.

HIV-positive patients should receive screenings for diabetes, osteoporosis, and colon cancer as needed. Monitoring and managing
lipid levels and other cardiovascular risk factors is essential.

Inform the patient about treatment side effects.

Treatment side effects depend on the medication and may include:
  CNS: cognitive and emotional alterations, sleep problems, headache
 GI: nausea, vomiting, diarrhea, liver damage
 Cardiovascular: heart disease
 Genitourinary: kidney injury
 Musculoskeletal: Weak bones or osteoporosis
 Laboratory: abnormal cholesterol levels, increased glucose

Administer prophylactic antimicrobials for opportunistic infections (OI).

Patients may require antibiotics or antifungal treatment to prevent certain infections when coupled with low CD4 counts.

Encourage the patient to avoid crowded places.

Avoid contact with large crowds (such as events and social gatherings) to prevent exposure to different infections, especially if CD4
counts are suboptimal.

POSSIBLE NURSING DIAGNOSIS

1. Disturbed Body Image related to low self-esteem as evidenced by altered social involvement
2. Imbalanced Nutrition related to inability to absorb nutrients as evidenced by body weight below ideal weight range for
age and gender
3. Ineffective Protection related to HIV infection as evidenced by decreased CD4 count

PROGNOSIS

Risk of AIDS, death, or both is predicted by the

 CD4 count in the short term

 Plasma HIV RNA level in the longer term

For every 3-fold (0.5 log 10) increase in viral load, mortality over the next 2 to 3 years increases about 50%. HIV-
associated morbidity and mortality vary by the CD4 count, with the most deaths from HIV-related causes occurring at
counts of < 50/mcL. However, with effective treatment, the HIV RNA level decreases to undetectable levels, CD4
counts often increase dramatically, and risk of illness and death falls but remains higher than that for age-matched
populations not infected with HIV (1). Hence, prompt diagnosis of HIV before the disease is too advanced and
immediate initiation of HIV treatment are essential to prognosis.

The prognosis of a patient with HIV and a CD4 count greater than 500 (normal) results in a life expectancy as someone
without HIV. A person with untreated AIDS has a life expectancy of about 1 to 2 years after the first opportunistic infection.
Antiretroviral treatment can increase CD4 counts and change the patient's status from AIDS to someone with HIV.