HIV AND AIDS

30 hrs
By Anne Mbithi
BS(Medical Education)

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 Learning Outcomes
At the end of this session the participant should be
able to:
I. Explain the global, regional, national and local
distribution of HIV
II. Discuss the distribution of HIV by age and sex
III. Discuss changes in morbidity and mortality due
to HIV/AIDS
IV. Describe the classification of ARVs
V. Describe the site of action of the various classes
of ARVs

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FUNDAMENTALS OF HIV AND AIDS
INTRODUCTION
• HIV: Human Immunodeficiency Virus.
• AIDS: Acquired Immune Deficiency
Syndrome.
• HIV disease is a spectrum of disorders ranging
from primary infection, asymptomatic state to
advanced disease.

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 Epidemiology

 HIV infection/AIDS is a global pandemic, especially in

developing countries. The current estimate of the number
of cases of HIV infection worldwide is ~33.2 million,
two-thirds of whom are in sub-Saharan Africa; ~50% of
cases are in women. Over the past decades HIV has
continued to be a growing public health problem
globally.
 In Kenya, over 1.5 million people are estimated to be
living with HIV, 900,000 of who were on antiretroviral
therapy by the end of 2015.
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 Human Immunodeficiency Virus:
Historical Background
1981 Doctors in US recognized PCP in homosexual
males, a condition previously unreported in
healthy adults
• Later recognized that all these patients were
immunosuppressed

1983/4 Scientist described the cause of this

acquired immunodeficiency syndrome
(AIDS) as a retrovirus
– Lymphadenopathy Associated Virus
(LAV)
– AIDs Associated Retrovirus (ARV)
– Human T- lymphotrophic Virus Ш
(HTLV-Ш)

1984 First case described In Kenya

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 Historical Background. ctd
1996 ARVs available in the world

1997 ARVs available in Kenya

private sector

2003 ARVs available in Kenya

public sector

2005 54,000 patients on ART

2010 Approx.426,870 patients on

ART
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 ETIOLOGY
• HIV/AIDS is caused by infection by the
human retroviruses HIV-1 or -2.
• HIV-1 is the most common cause worldwide;
HIV-2 has about 40% sequence homology

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 Retroviruses
HTLV-I HIV-1

HTLV-II HIV-2

STLV- I SIV

Cell proliferation Cell death

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 HIV Virus
• A retrovirus from the Lentivirus family.

• Genetic material consists of a single-

stranded ribonucleic acid (RNA)

• Viral particle is spherical in shape with a

diameter of 80-100 nanometers (nm).

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Types of Human Immunodeficiency Virus
Basic Virology:
There are two types of HIV.
• HIV – 1
– Is found worldwide
– Is the main cause of the worldwide pandemic
• HIV – 2
– Is mainly found in West Africa, Mozambique and Angola.
– Causes a similar illness to HIV – 1
– Less efficiently transmissible rarely causing vertical
transmission
– Less aggressive with slower disease progression

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 HIV -1 Subtypes
• HIV-1 has many subtypes: A-K
• A-E are the predominant subtypes
– A: W. Africa, E. Africa, Central Africa East Europe &
Middle East
– B: N. America, Europe, Middle East, E. Asia, Latin
America
– C: S. Africa, S. Asia, Ethiopia
– D: E. Africa
– E: S. E. Asia

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East and Central Africa
has mainly subtype A
and D.

Southern Africa mainly

subtype C.

West Africa mainly A

Different subtypes can

combine to form diverse
recombinants.

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 Structure of Human Immunodeficiency
Virus
 Has an outer double lipid membrane, (derived
from the host membrane).
 The lipid membrane is lined by a matrix
protein.
 The lipid membrane is studded with the surface
glycoprotein (gp) 120 and the transmembrane
gp 41 protein.
 These glycoprotein spikes surround the cone-
shaped protein core.
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 Structure Of Human
Immunodeficiency Virus

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15
 HIV Structure
HIV Glycoproteins
• The gp120 and gp41 mediate the entry of
virus into the host cells.
The core (capsid) is made up of several proteins:-

 P24 the main protein

 Within the capsid are
 two identical single strands of RNA (the viral genetic material).
 viral enzymes

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 HIV Structure
Viral Enzymes
• Most important: Reverse Transcriptase (RT), Protease and
Integrase.
• RT converts viral single-stranded RNA into a double
stranded deoxyribonucleic acid (DNA).
• DNA is incorporated into host nucleus as the proviral DNA.
• Integrase facilitates integration of the DNA into the host’s
chromosomal DNA.
• Protease enzyme splits generated macro-proteins into
smaller viral proteins (core, envelope & regulatory proteins
and enzymes) which go into forming new viral particles.

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• It is necessary for a double stranded DNA
chain to be formed so that it can be integrated
into the double stranded host DNA. This step
is catalyzed by RT which also acts as a DNA
polymerase. This is essential for the
integration process since the host DNA is a
double stranded structure. In this way the
virus establishes an infection that is not
eradicable unless the host cell dies.
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 HIV Life cycle
 Binding, Fusion and Entry
 Transcription
 Integration & Replication
 Budding
 Maturation

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20
 HIV Life Cycle
BINDING:
• For successful entry into cells the HIV
envelope glycoprotein GP 120 binds to the
host receptor CD4 molecule
– co-receptors are necessary (CCR5/CXCR4).

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 HIV Life Cycle
FUSION and ENTRY:
• Viral binding to host cell triggers fusion of the
viral and host cell membranes
– Mediated by gp41
• Allows entry of virus core into host cell
cytoplasm
• Core protein dissolved by host enzymes
releasing viral RNA and enzymes

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 HIV Life Cycle
INTEGRATION
• Reverse transcriptase converts the viral RNA
into a DNA molecule

• The DNA enters the host cell nucleus

• Integrase catalyses the process of integration

of the viral DNA into the host cell’s DNA

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 HIV Life Cycle
REPLICATION
• Integrated viral DNA turns the host cell into a
"factory" for manufacturing more virus.

• Viral proteins are produced as a single multi-

protein molecule
– Viral proteins cleaved by protease enzyme

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 HIV Life Cycle
Budding and Maturation:
• Viral proteins together with RNA gather at the
membrane of the CD4+ cells
• Viral particles are formed which bud off the
cell and enter the bloodstream
• The CD4 cells are often destroyed by HIV virus
infection and replication resulting in profound
immunodeficiency.

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 Transmission - HIV
(homo/bisexual
Male Male Female
(homo/bisexual) (heterosexual) (infected blood/tissue)

Male
(infected blood/tissue)
Female

Male/Female
(homosexual
Child

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• HIV can be transmitted in the body through
these fluids:
• Semen
• Vaginal fluids
• Blood
• Breast milk
• Amniotic fluids.

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1. Sexual Transmission
• Unprotected sexual intercourse with infected person.
• Direct contact with body fluids of infected person. (blood,
semen, vaginal secretions)
• Note: Sexual transmission accounts for 87% of HIV transmission
worldwide.
2. Mother to Child transmission
• During pregnancy
• During labour and delivery(most mother to child transmission
occurs at this stage).
• During breast feeding.
3. Use of unsafe sharp objects.
• Injecting drugs and sharing needles with an infected person.
• Piercing, tattooing or cutting with unclean knives or other
objects.
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Ways HIV is NOT transmitted

• Sharing food or a drinking cup.

• Hugging
• Kissing
• Shaking hands
• Coughing or sneezing
• Being near a PLWHA
• Sharing latrines
• Mosquitoes or insect bites even if they carry human
blood. HIV cannot live outside humans.
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Mechanisms for Maternal
to Fetal Transmission

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 Risk factors for HIV infection
• Unprotected sex – vaginal and anal sex.
• Multiple sex partners.
• STI infected people especially STIs that cause ulcerations
like herpes, chancroid and syphillis.
• Use of intravenous drugs, Sharing needles.
• Children born to HIV positive mothers.
• Uncircumcised male.
• Alcohol and drug addiction.
• HCWs where precautions are neglected or fail eg. Not
using gloves or accidental needle stick injuries.
• Blood transfusions especially where blood is not
adequately screened.
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 Most At Risk Populations for HIV infection. (MARPS)
• Injection drug users
• Sex workers and their clients.
• Men who have sex with men
• Prisoners
• Female sex workers
These groups are more vulnerable to HIV infection due a variety
of factors such as:
- More frequent exposures to the virus.
- Involvement in risky behavior.
- Potentially weak family and social support systems,
- Marginalization.
- Lack of resources
- Inadequate access to health care services,
- Stigma and Criminalization. 32
 Myths And Misconceptions about HIV/AIDS
Myth: A widely held but false belief. An idea or story
that is believed by many people but that is not true.
Misconception: A conclusion that is wrong because it’s
based on faulty thinking or facts that are wrong.

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 Myths and Misconceptions about HIV/AIDS
• HIV is spread through
-Breathing the same air
-Drinking from same cup or fountain
-Hugging kissing
-Sharing utensils
• Mosquitoes spread HIV
• You cant get HIV from oral sex
• I don’t need to worry about getting HIV, drugs will
keep me better.
• If am getting treatment, I cant spread the virus.
• My partner and I are both HIV positive, so we don’t
have to practice safe sex. 34
PATHOPHYSIOLOGY

The hallmark of HIV disease is a profound

immunodeficiency resulting from a progressive quantitative
and qualitative deficiency of the subset of T lymphocytes
referred to as helper or inducer T cells.

This subset of T cells is defined phenotypically by the

expression on the cell surface of the CD4 molecule, which
serves as the primary cellular receptor for HIV.

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ctd Pathophysiology

A co-receptor must be present with CD4 for efficient entry

of HIV-1 into target cells. The two major co-receptors for
HIV-1 are the chemokine receptors CCR5 and CXCR4.

Although the CD4+ T lymphocyte and CD4+ monocyte

lineage are the principal cellular targets of HIV, virtually any
cell that expresses CD4 along with one of the co-receptors
can potentially be infected by HIV; however, viral replication
is not efficient in these other cell types.
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 CLINICAL MANIFESTATIONS OF HIV
INFECTION
Acute HIV (Retroviral) Syndrome:

 Approximately 50–70% of infected individuals experience an

acute syndrome following primary infection. The acute syndrome
follows infection by 3–6 weeks. It can have multiple clinical
features.
 It lasts 1–2 weeks, and resolves spontaneously as an immune
response to HIV develops and the viral load diminishes from its
peak levels.
 Most pts will then enter a phase of clinical latency, although an
occasional pt will experience rapidly progressive immunologic
and clinical deterioration.
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 Clinical Findings In The Acute Hiv
Syndrome
Neurologic
General
• Meningitis
• Fever
• Encephalitis
• Pharyngitis
• Peripheral neuropathy
• Lymphadenopathy
• Headache/retroorbital • Myelopathy
pain Dermatologic
• Arthralgias/myalgias • Erythematous
• Lethargy/malaise maculopapular rash
• Anorexia/weight loss • Mucocutaneous
• Nausea/vomiting/diarrhea ulceration
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 Asymptomatic Infection
 The length of time between HIV infection and
development of disease varies greatly, but the median is
estimated to be 10 years in untreated individuals.
 HIV disease with active viral replication usually
progresses during this asymptomatic period, and CD4+ T
cell counts fall.
 The rate of disease progression is directly correlated
with plasma HIV RNA levels.
 Pts with high levels of HIV RNA progress to symptomatic
disease faster than do those with low levels of HIV RNA.

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Symptomatic
 In general, the spectrum of illness changes as
the CD4+ T cell count declines. The more severe and life-threatening
complications of HIV infection occur in patients with a CD4+ T cell count <
200/μl.

 The key element to treating symptomatic complications of HIV

disease, whether primary or secondary, is achieving good control of
HIV replication through the use of combination antiretroviral
therapy and instituting primary and secondary prophylaxis as
indicated.

 Major clinical syndromes seen in the symptomatic stage of HIV

infection are summarized below.
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 Major clinical syndromes seen in the
symptomatic stage of HIV infection include:
 Persistent generalized lymphadenopathy: Palpable
adenopathy at two or more extrainguinal sites that
persists for >3 months without explanation other than
HIV infection. Many pts will go on to disease
progression.
 Constitutional symptoms: Fever persisting for >1
month, involuntary weight loss of >10% of baseline,
diarrhea for >1 month in absence of explainable cause.

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Neurologic disease: Most common is HIV
encephalopathy (AIDS dementia complex); other
neurologic complications include opportunistic
infections, primary CNS lymphoma, CNS
Kaposi’s sarcoma, aseptic meningitis,
myelopathy,peripheral neuropathy and
myopathy.

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 Ctd:
 Secondary infectious diseases: P. jiroveci pneumonia
is most common opportunistic infection, occurring in
~80% of untreated individuals during the course of their
illness. Other common pathogens include CMV
(chorioretinitis,colitis,pneumonitis, adrenalitis),
Candida albicans (oral thrush, esophagitis), M.avium
intracellulare (localized or disseminated infection), M.
tuberculosis, Cryptococcus neoformans (meningitis,
disseminated disease), Toxoplasma gondii (encephalitis,
intracerebral mass lesion), herpes simplex virus (severe
mucocutaneous lesions, esophagitis), diarrhea due to
Cryptosporidium spp. or Isospora belli, bacterial
pathogens (especially in pediatric cases). 43
 Secondary neoplasms: Kaposi’s sarcoma
(cutaneous and visceral, more fulminant course than
in non-HIV-infected pts), lymphoid neoplasms
(especially B cell lymphomas of brain, marrow, GI
tract).

 Other diseases: A variety of organ-specific

syndromes can be seen in HIVinfected pts, either as
primary manifestations of the HIV infection or as
complications of treatment
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 HIV Diagnosis
TYPE OF TESTS HIV MARKERS YEAR OF TEST DURATION
INTRODUCTION
(in Hours)

ELISA Gp 120, gp 41, p24, Early 1980s 2-3

gp 36.

Western Blot All HIV Markers Early 1980s 48

Viral Culture Tissue Culture Mid 1980s 72

P24 Antigen Assay Gag p24 Late 1980s 3

DNA PCR RNA Early 1990s 12

RT PCR RNA Mid 1990s 12

Rapid Tests gp 120, gp 41, p24 Late 1990s 40 Minutes.

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HIV Treatment
Antiretroviral Therapy
• The cornerstone of medical management of HIV infection is
highly active combination antiretroviral therapy, or HAART.

Aims of Treatment
• Improved quality of life/increased longevity

• Reduction of HIV related morbidity and mortality

• Restoration and preservation of immune function

• Maximal suppression of HIV replication

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 Principles of ARV Treatment
• Antiretroviral treatment is part of the comprehensive
care of HIV infection
• Treatment should be planned and started in good
time
• Regular follow up and monitoring is essential
• Treatment should be stopped/changed when
necessary
• The choice of drugs should take into account
– Efficacy
– Tolerability
– Dose Schedule
– Affordability and availability
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Ctd: Principles of ART
• ARV drugs are associated with adverse events and
drug-drug interactions
• Atleast 3 different drugs are included in an ART
regimen referred to as HAART- Highly Active Anti
Retroviral Therapy.
• Adherence is key to successful treatment
• Treatment may fail despite patient’s and carer’s best
efforts
• There should be commitment to continued support of
patient (and family)
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 Characteristics of good HAART
• Potent: should bring down viral load to an undetectable
level within 3-4 months of therapy

• Acceptable regimen to maximize adherence

- simple
- tolerable side effects
- patient commitment for life-long therapy

• Reasonable options for future therapy

• Affordable and sustainable

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 NOTE!
• Currently HAART does not cure HIV but
halts viral replication, thus prevent
further disease progression and
immune system damage

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 Suppression of HIV Replication
• ARVs must be taken in combination of at least
3 drugs
• Strict adherence to treatment is of the utmost
importance
– <95% adherence allows the rapid development of
viral resistance
– Poor adherers do badly
• Fail treatment much earlier

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Immune Reconstitution

• ART prevents CD4 destruction by HIV

• CD4 cell count can recover
• Improved function of CD4 cells
• CD4 cells are central to the immune system
– So there is improved overall function of the
immune system
– It takes from 6 to 8 weeks for this to become
evident clinically

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 Reduction of HIV related morbidity and
mortality and Improvement of QOL –
Quality of Life.
• Decreased hospitalizations
• Decreased risk of illnesses
• Increased general well-being
• Reversal of weight loss
• Ability to return to work

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Classes of Anti Retro Virals

• Reverse transcriptase (RT) inhibitors

– Nucleoside RT inhibitors (NRTI)
– Non-nucleoside RT inhibitors (NNRTI)
– Nucleotide RT inhibitors (NtNRI)
• Protease inhibitors (PI)
• Entry Inhibitors
– Attachment inhibitors
– Chemokine receptor antagonists
– Fusion inhibitors
• Integrase inhibitors
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 Antiretroviral Agents
• NRTI (Nucleoside/Nucleotide Reverse Transcriptase
Inhibitor): Block the enzyme reverse transcriptase from
converting HIV genetic material RNA into human
genetic material DNA, thus prevents further production
of HIV RNA copies that can infect other cells.

• Examples of NRTIs.

– Zidovudine (AZT,ZDV)
– Didanosine (ddI)
– Zalcitabine (ddC)
– Stavudine (d4T )
– Lamivudine (3TC)
– Abacavir (ABC)
– Emtricitabine (FTC) 55
 Ctd: ARVs
• NNRTI (Non-Nucleoside Reverse Transcriptase
Inhibitor): Inhibit reverse transcriptase by
changing the shape of the viral enzyme to
decrease its activity.

– Nevirapine (NVP)
– Delavirdine (DLV)
– Efavirenz (EFV)

• Nucleotide analogues
– Tenofovir (TDF)

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 Ctd: ARVs
• PI: Protease Inhibitors. Try to stop the activity of viral
protease responsible for creating new HIV RNA particles,.
Examples;
– Saquinavir (SQV)
– Ritonavir (RTV)
– Indinavir (IDV)
– Nelfinavir (NFV)
– Amprenavir (APV)
– Lopinavir/ ritonavir (LPV/r)
– Atazanavir (ATV)
– Darunavir(DRV)

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 Ctd: ARVs
• Fusion/ Entry inhibitors: Block the HIV envelope from
merging with the host CD4 cell membrane (fusion). This
prevents HIV from entering the CD4 cells.
– Enfuvirtide (T-20)
Maraviroc
Vicroviroc

• Integrase inhibitors: Inhibit action of integrase, a viral

enzyme that inserts the viral genome into DNA of the host
cell.
-Raltegravir

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 Some ARVs as Fixed Drug Combinations
(FDCs)
• AZT + 3TC
• d4T+3TC
• AZT + 3TC + NVP
• d4T + 3TC + NVP
• d4T + 3TC + NVP
• TDF + FTC + EFV
• TDF + FTC
• ABC + 3TC
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 Monitoring ART
Why?
• Assess efficacy of intervention
• Detect other treatable conditions
• Assessment for drug related toxicities
How?
• Clinical history and examination
• Laboratory markers

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 Clinical Monitoring
• Regular clinical evaluation is important to
– Assess efficacy of ART
– Monitor toxicity.

Frequency of visits for clinical monitoring

• First visit at 2 weeks after initiating therapy
– Ensure that medicines are being taken and stored
correctly
– Note and address possible side effects
– Assess adherence

• In stable patients
– Subsequent visits should be monthly
– 6-12 months following initiation of ART, clinical
appointments may be spaced at 2 to 3 month intervals in
compliant and clinically stable patients with an excellent61
 Ctd: Clinical Monitoring
• Plot the patient’s weight and note the trend
– Falling weight may indicate treatment failure/new illness
e.g. TB
• Determine the patient’s physical condition.
– Address ongoing medical problems including possibility
of failure of treatment through the development of new
OIs.
– Treat inter-current infections
• Check drug dosages and adjust according to weight.
• The patients should be given medicines to last preferably for
1 month even when the clinic appointments are less frequent
and patient should come to pick the medicines on monthly
basis
Adherence should be assessed and appropriate counseling
provided at EACH visit.

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 Ctd: Clinical Monitoring
Look for:
• Patient self assessment of well being
• Decrease or disappearance of symptoms
• Increase in body weight
• Decrease in frequency and severity of
Opportunistic Infections

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 Laboratory Monitoring of ART
Laboratory tests are recommended for
• Assessing response to and efficacy of
treatment.
• Monitoring toxicity

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 Laboratory Monitoring of ART
Assessing efficacy of treatment
• For effective monitoring of efficacy of
treatment, CD4 counts, and viral load are
essential.

• Resistance testing where available is a useful

adjunct to choice of antiretroviral treatment.

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Lab Tests: Monitoring For Toxicity
• CD4 count should be determined at baseline or as
soon as possible and thereafter at 6 monthly
intervals.
• CD4 count should not be measured during a
concurrent infection
– Delay until > 2 weeks after recovery
• For consistency CD4 measurements in a patient
should be carried out
– In the same laboratory and preferably at the same time of
day.

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 Laboratory Monitoring of ART:
Viral Load
• Viral load measurements are the most timely and
sensitive way of assessing treatment response
• Viral load should also be done,
- Clinical failure is suspected OR
- Immunological failure is suspected.

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Lab Tests: Monitoring For Toxicity
Hematological and biochemistry Tests for
monitoring toxicity
• Where available the following tests should be
done at baseline and while on ART to enable
monitoring ARV drug toxicity
• The clinical picture should always be taken
into account when monitoring for toxicity

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