Human Immunodeficiency Virus

(HIV) and Opperortunistic infection

Bikash kumar sah

M-Pharm 3rd Semester
PUCMAS
Gothgaun, Morang
 Contents
• Introduction
• Epidemiology of HIV/AIDS
• Causes
• Pathophysiology
• Sign and symptoms
• Diagnosis
• Treatments
INTRODUCTION
 INTRODUCTIONS
• The Human Immunodeficiency Virus or HIV virus as it is
commonly known is a unique type of virus (a retrovirus).

• HIV is a blood borne retrovirus and is transmitted through sexual

contact, contaminated blood transfusions, injecting drug use, failure
to observe what are now termed in medical circles “universal
precautions”, and from mother to infant during pregnancy, delivery
and breastfeeding.

• The human immunodeficiency virus is a lentivirus that causes the

acquired immunodeficiency syndrome(AIDS),

• AIDS is a condition in humans in which progressive failure of the

immune system allows life-threatening opportunistic infections and
cancers to thrive.
 Contd….

• Invades the helper T cells (CD4 cells) in the body of the host
(defense mechanism of a person)

• AIDS is also called slim diseases caused by retrovirus known

as HIV.

• IT destroy specific blood cells called CD4 + T helper cell

which are crucial for fighting Diseases.

• AIDS Predisposes our body to other opportunistic infections.

 Contd….
• Hiv virus is 1/10000th of a mm in diameter.

• The virus replicates in t4 lymphocytes and can

destroy T4 helper cells a subset of T
lymphocytes.

• It can cross BBB and accounts for neurological

and Psychological abnormalaities.
 Epidemiology of HIV/AIDS
• AIDS was first described in 1981, when previously healthy young
adults – mainly men living in urban areas of the United States –
began falling ill with opportunistic infections previously unknown
among this age group.

• Similar infections were soon described in Africa, the Caribbean

and Europe; AIDS was clearly an epidemic disease.

• In 1983, Professor Luc Montagnier and others discovered a novel

pathogen: a retrovirus tropic for the CD4 cells that orchestrate
cell-mediated immunity and protect humans from a broad range
of viral mycobacterial, and fungal pathogens.
 Contd….
• It is estimated that during the course of 2002 some 5 million
people became infected with HIV, and almost 3 million people
died of AIDS.

• The global prevalence of HIV has increased from 31.0 million

in 2002, to 35.3 million in 2012, because people on
antiretroviral therapy are living longer,5 whereas global
incidence has decreased from 3.3 million in 2002, to 2.3
million in 2012.

• Global AIDS related deaths peaked at 2.3 million in 2005, and

decreased to 1.6 million by 2012
Fig showing epidemiology of HIV/AIDS
Estimated number of people living with HIV in 2012 and trends in the incidence of
new infections from 2001 to 2012 by global region Data from UNAIDS 2013 report
 PATHOPHYSIOLOGY
There are two major types of the human immunodeficiency
virus. HIV-1, which was discovered first, is the most
widespread type worldwide. HIV-2 is more than 55%
genetically different from HIV-1.

HIV-1 comprises groups M (main), O (outlier), and N (non-M or

O).

There are two main HIV-2 subtypes, A and B.

Contd….
 Contd….

• Human immunodeficiency virus (HIV)–1 is a member of the Retroviridae family.

It is an enveloped virus with two copies of single-stranded RNA, which have
capacity to recombine.

• The genome contains 3 major genes that encode structural proteins: gag,

pol, and env. 

> The gag gene encodes for p24, p17, and p7, among.

> The env gene encodes for glycoprotein (gp) 120 and gp 41.
> The pol gene encodes the enzymes reverse transcriptase, integrase, and
protease.

• HIV-1 also has regulatory genes (tat and rev) and genes that encode for
accessory proteins (vpu, vpr, vif, and nef) that are important in viral replication
and interaction with the host.

• HIV-2 shares the same genes with HIV-1 with the exception of vpu.
 Contd….
• The main target of HIV is activated CD4 T-lymphocytes; entry
is via interactions with CD4 and the chemokine coreceptors,
CCR5 or CXCR4.

• Other cells bearing CD4 and chemokine receptors are also

infected, including resting CD4 T cells, monocytes and
macrophages, and dendritic cells.

• CD4- independent HIV infection of cells can happen, notably

in astrocytes and renal epithelial cells, and subsequent HIV
gene expression has an important role in the pathogenesis of
HIV-associated neurocognitive disorder (related to astrocytes)
and nephropathy (related to epithelial cells).
 Contd….

• Transmission of HIV across mucosal membranes is usually

established by one founder virus, which has unique
phenotypic properties including usage of CCR5 rather than
CXR4 for entry, enhanced interaction with dendritic cells, and
resistance to interferon-α.

• Transmission of the founder virus is followed by a rapid

increase in HIV replication and then a striking induction of
inflammatory cytokines and chemokines, which is in stark
contrast to the minimum initial response to other chronic viral
infections such as hepatitis B or hepatitis C
 SIGN AND SYMPTOMS
It can be explained through four clinical stages
Clinical stage 1: Asymptomatic
Clinical stage 2: Mild symptoms
Clinical stage 3: Advanced symptoms
Clinical stage 4: Severe symptoms
 Clinical stage 1: Asymptomatic

• Asymptomatic Persistent generalized

lymphadenophathy
 Clinical stage 2: Mild symptoms

• Moderate unexplained weight loss (less than 10% of body

weight)
• Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis
media, pharyngitis)
• Zona (Herpes zoster)
• Angular cheilitis
• Recurrent oral ulceration
• Papular pruritic eruption
• Seborrhoeic dermatitis
• Fungal nail infections
 Clinical stage 3: Advanced symptoms
• Unexplained severe weight loss (more than 10% of body weight)
• Unexplained chronic diarrhoea for longer than one month.
• Unexplained persistent fever (intermittent or constant and lasting for
longer than one month).
• Recurrent oral candidiasis.
• Oral hairy leukoplakia.
• Pulmonary tuberculosis.
• Severe bacterial infections (pneumonia, empyema, pyomyositis,
bonejoint infection, meningitis, septicemia).
• Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis.
• Unexplained anaemia (< 80g/L), neutropenia (< 0.5x109/L), and/or
chronic thrombocytopenia (< 50x109/L).
 Clinical stage 4: Severe symptoms
• HIV wasting syndrome (loss of more than 10% of body weight with
prolonged & unexplained fever or diarrhoea of more than one month
duration).
• Pneumonia caused by Pneumocystis jiroveci (PCP).
• Chronic herpes simplex virus infection (orolabial, genital or anorectal) of
more than one month duration, or visceral at any site
• Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs).
• Extrapulmonary tuberculosis
• Kaposi’s sarcoma
• Diseases due to Cytomegalovirus (CMV) in retina or other organs.
• Toxoplasmosis in central nervous system.
• HIV encephalopathy.
• Extrapulmonary cryptococcosis including meningitis.
 Contd….

• Disseminated disease due to Mycobacteria avium complex (MAC).

• Progressive multifocal leukoencephalopathy (PML).
• Chronic diarrhea due to Cryptosporidia.
• Chronic diarrhea due to Isospora
• Disseminated mycosis (penicilliosis, extrapulmonary histoplasmosis).
• Recurrent septicemia (including nontyphoid salmonellosis).
• Cerebral or B cell nonHodgkin lymphoma.
• Invasive cervical carcinoma.
• Atypical disseminated leishmaniasis.
• HIVassociated nephropathy.
• Myocarditis due to HIV.
Immunological stages
 Stages of HIV Infections
• There are three stages of HIV infection:
• Acute HIV Infection

This is the earliest stage of HIV infection, and it generally

develops within 2 to 4 weeks after infection with HIV. During this
time, some people have flu-like symptoms, such as fever, headache,
and rash. In the acute stage of infection, HIV multiplies rapidly and
spreads throughout the body. The virus attacks and destroys the
infection-fighting CD4 cells of the immune system. During the acute
HIV infection stage, the level of HIV in the blood is very high, which
greatly increases the risk of HIV transmission. A person may
experience significant health benefits if they start ART during this
stage.
 Contd….
• Chronic HIV Infection

The second stage of HIV infection is chronic HIV infection (also

called asymptomatic HIV infection or clinical latency).

During this stage, HIV continues to multiply in the body but at very
low levels. People with chronic HIV infection may not have any HIV-
related symptoms. Without ART, chronic HIV infection usually
advances to AIDS in 10 years or longer, though in some people it
may advance faster. People who are taking ART may be in this stage
for several decades. While it is still possible to transmit HIV to
others during this stage, people who take ART exactly as prescribed
and maintain an undetectable viral load have effectively no risk of
transmitting HIV to an HIV-negative partner through sex.
 Contd….
• AIDS

AIDS is the final, most severe stage of HIV infection.

Because HIV has severely damaged the immune system,
the body can’t fight off opportunistic infections.
People with HIV are diagnosed with AIDS if they have a
CD4 count of less than 200 cells/mm3 or if they have
certain opportunistic infections. Once a person is
diagnosed with AIDS, they can have a high viral load
and are able to transmit HIV to others very easily.
Without treatment, people with AIDS typically survive
about 3 years.
 DIAGNOSIS
• HIV infection in adults is diagnosed on the basis of laboratory
detection of antiHIV antibody.

• A person is defined as infected with HIV when his/her serum

specimen is reactive in all three anti HIV antibody tests, which
rely on different antigens or of different operating
characteristics.
Contd….
Contd….
 TREATMENTS
The classes of anti-HIV drugs include:
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) turn off a
protein needed by HIV to make copies of itself.
Examples include
efavirenz ,
etravirine and
nevirapine

• Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are

faulty versions of the building blocks that HIV needs to make copies of
itself.
Examples include
# Abacavir and the combination drugs emtricitabine/tenofovir , Descovy
(tenofovir alafenamide/emtricitabine), and
# lamivudine-zidovudine
 Contd….
• Protease inhibitors (PIs) inactivate HIV protease, another protein that HIV needs to
make copies of itself. Examples include
• atazanavir (Reyataz),
• darunavir (Prezista),
• fosamprenavir (Lexiva) and
• indinavir (Crixivan).

• Entry or fusion inhibitors Tblock HIV's entry into CD4 T cells.

Examples include enfuvirtide (Fuzeon) and
maraviroc (Selzentry).

• Integrase inhibitors work by disabling a protein called integrase, which HIV uses to

insert its genetic material into CD4 T cells.
• Examples include
raltegravir (Isentress) and
dolutegravir (Tivicay).
NNRTIs
NRTIs
Proteases Inhibitors
Integrase Inhibitors
Mechanism of action of anti viral drugs
 Description of Entry Inhibitors
• The process of HIV-1 entry into host cells is complex; each
step presents a potential target for inhibition. Viral
attachment to the host cell entails binding of the viral
envelope glycoprotein complex gp160 (consisting of gp120
and gp41) to its cellular receptor CD4. This binding induces
conformational changes in gp120 that enable access to the
chemokine receptors CCR5 or CXCR4.

• Chemokine receptor binding induces further conformational

changes in gp120, allowing exposure to gp41 and leading to
fusion of the viral envelope with the host cell membrane and
subsequent entry of the viral core into the cellular cytoplasm.
 Description of NRTI
• The NRTIs act by competitive inhibition of HIV-1 reverse
transcriptase; incorporation into the growing viral DNA chain
causes premature chain termination due to inhibition of
binding with the incoming nucleotide ( Figure 49–4 ). Each
agent requires intracytoplasmic activation via phosphorylation
by cellula enzymes to the triphosphate form.

• All NRTIs may be associated with mitochondrial toxicity,

probably owing to inhibition of mitochondrial DNA
polymerase gamma.
 Description of nNRTI
• The NNRTIs bind directly to HIV-1 reverse transcriptase,
resulting in allosteric inhibition of RNA- and DNA dependent
DNA polymerase activity. The binding site of NNRTIs is near to
but distinct from that of NRTIs. Unlike the NRTI agents,
NNRTIs neither compete with nucleosid triphosphates nor
require phosphorylation to be active.
 Description of PI
• During the later stages of the HIV growth cycle, the gag and gag - pol gene
products are translated into polyproteins, and these become immature
budding particles.

• The HIV protease is responsible for cleaving these precursor molecules to

produce the final structural proteins of the mature virion core. By
preventing post-translational cleavage of the Gag-Pol polyprotein,
protease inhibitors (PIs) prevent the processing of viral proteins into
functional conformations, resulting in the production of immature,
noninfectious viral particles. Unlike the NRTIs, PIs do not need intracellular
activation.
Drugs used For Treatments and Preventions
Contd…..
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PREVENTIONS
Opportunistic Infections
• https://www.aidsmap.com/about-hiv/hiv-1-an
d-hiv-2
• Katzung G, Susan B and Trevor A. Basic and Clinical Pharmacology. 12th
edition The McGraw-Hill; PP 861-882.

• Novotny L et al,. Antiretroviral therapeutics with different

mechanisms of action on HIV infection. Research Journal of
Pharmaceutical, Biological and Chemical Sciences 2016: 7(2) ; 90.

• Maartens G,Celum C and Lewin SR. HIV infection: epidemiology,

pathogenesis, treatment, and prevention. The Lancet 2014; 384: 258–71.