HIV is the causative agent of AIDS and is a leading cause of death worldwide. Here is a brief summary of AIDS. Hope it will be helpful. Thanks

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By Sehrish Zahid

2. Definition
• The acquired immune deficiency
syndrome (AIDS) is the state of profound
immunosuppression produced by
chronic infection with human
immunodeficiency virus (HIV).
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3. Epidemiology
• In June 1981, five cases of Pneumocystis jiroveci (formerly known as
carinii) pneumonia (PCP) were reported.
• Reports of other unusual conditions, such as Kaposi's sarcoma (KS),
followed shortly.
• In each of these patients, there was found to be a marked impairment
of cellular immune response, and so the term acquired immune
deficiency syndrome, or AIDS, was coined.
• In 1984, a new human retrovirus, subsequently named human
immunodeficiency virus (HIV), was isolated and identified as the
cause of AIDS.
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4. Isolation of HIV
• The virus has been isolated from a number of body fluids, including:
i. blood,
ii. saliva,
iii. Tears,
iv. urine,
v. semen,
vi. vaginal secretions,
vii. breast milk,
viii. peritoneal fluid and
ix. cerebrospinal fluid (CSF).
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5. Routes of HIV Transmission
• Predominant routes of transmission:
i. Copulation
ii. Sharing of unsterilized needles or syringes
iii. Blood or blood products (unscreened/unsterilized)
iv. Vertical transmission in utero
v. During labor
vi. Through lactation
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6. HIV
Structure
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7. HIV Life-Cycle
1. Binding:
On the surface of T-cell, HIV binds to a CD4 receptors by the
help of gp-41 and one of the two co-receptors- CXCR4 or CCR5
2. Fusion:
The virus fuses with the host cell membrane and releases its
genetic material (RNA) and enzymes into the cell.
3. Reverse Transcription:
The single-stranded HIV RNA is converted into double-
stranded HIV by the reverse transcriptase enzyme. 7

8. 4. Integration:
After the HIV DNA enters the cell’s nucleus, the enzyme integrase cuts the
cell’s DNA and inserts the HIV into it forming a provirus.
5. Transcription and Translation:
The enzyme RNA polymerase makes RNA copies of DNA, HIV RNA is either
inserted into new virus particles or processed and translated into HIV proteins.
6. Assembly:
The long protein chains are cut into individual proteins by the enzyme
HIV protease. A new virus is assembled with these proteins and HIV RNA.
7. Release:
The new virus particle is released from the host cell, taking with it part of
the cells membrane, and capable of infecting other cells.
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10. Disease Progression
• Immediately after primary HIV Infection (PHI, also known as
‘seroconversion’), there is a very high rate of viral turnover.
• Equilibrium is then reached, at which stage the infection may appear
to be clinically latent, but in fact, as many as 10,000 million new
virions are produced each day.
• Over time, as chronic infection ensues, cells possessing CD4
receptors, particularly the T-helper lymphocytes, are depleted from
the body.
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11. Disease Progression
• The individual becomes susceptible to a myriad of infections and
tumors.
• The rate at which this immunosuppression progresses is variable and
the precise interaction of factors affecting it is still not fully
understood.
• It is likely that a combination of viral, host (genetic) and
environmental factors contributes to this variation.
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12. Clinical Manifestations
The sequelae of untreated HIV infection can be broadly considered in five
categories:
1. Opportunistic infections, e.g., P. jiroveci pneumonia (PCP) and cytomegalovirus
(CMV).
2. Infections that can occur in immune-competent patients but tend to occur
more frequently, more severely, for example, Salmonella, herpes simplex and
Mycobacterium tuberculosis.
3. Malignancies, for example, Kaposi's sarcoma and non-Hodgkin's lymphoma.
4. Direct manifestations of HIV infection, for example, HIV encephalopathy, HIV
myelopathy and HIV enteropathy.
5. Consequences of chronic immune activation including premature
cardiovascular disease, neurocognitive dysfunction, bone mineral density loss.
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13. Symptoms
• In addition, approximately 70% of individuals develop a flu-like illness
at seroconversion.
• This primary HIV infection (PHI) is characterised by:
• fever,
• arthralgia,
• pharyngitis,
• rash
• lymphadenopathy.
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14. Patients’ Classification According to Clinical Status
• Patients can be classified into one of three groups according to their
clinical status:
1. Asymptomatic
2. Symptomatic
3. AIDS
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15. • Symptomatic disease is characterized
1. By non-specific symptomatology such as
a) Fever,
b) Night sweats
c) Lethargy
d) Weight loss, or
2. By complications including
a) oral candidiasis
b) oral hairy leukoplakia
c) recurrent herpes simplex or herpes zoster infections.
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16. • AIDS is defined by the diagnosis of one or more specific
conditions including
i. P. jiroveci pneumonia (PVP),
ii. M. tuberculosis infection &
iii. CMV disease.
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17. Investigations and Monitoring
1. Current and Previous Infections
2. CD4 Count
3. Viral Load (HIV RNA)
4. Resistance Testing
5. Tropism Tensting
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18. 1. Current & Previous Infections
Detection of antibodies
against HIV
Within 3-4 weeks of
infection
‘Window Period’ of 3
months is req. for
confirmation
Test for prior exposure to
number of potential
pathogens
Syphilis, Hepatitis A, B and
C, CMV, Varicella zoster
virus, T. gondii.
This can enable subsequent
Treatment
(in case of undiagnosed
syphilis)
Vaccination
(if no prior exposure to
hepatitis A, B, or VZV),
Prevention
(if no prior exposure to
Toxoplasma and CMV)
Prophylaxis
(if previous exposure to
Toxoplasma)
Diagnosis
(according to CMV or
Toxoplasma status).
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19. 2. CD4 count
Level of
immunosuppression is
estimated
By measuring the
number of CD4-positive
T-lymphocytes
In the sample of
peripheral blood
Normal range can vary
between 500 and 1500
cells/mm3
Particular complications
of HIV infection usually
begin to occur at CD4
counts specified in graph
Can assist in differential
diagnoses
And enable the use of
prophylactic therapies.
CD4 count can be used
as the major indicator of
when to consider
starting antiretroviral
therapy.
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21. 3. Viral Load (HIV RNA)
Estimates amount of
circulating virus in the
blood
Correlates with
prognosis
High viral load predicts
faster disease
progression
Reduction in viral load
after commencement of
antiviral therapy is
associated with clinical
benefit
Helps in making
decisions regarding
when to start and when
to change antiviral
therapies
And enabling more
effective use of antiviral
agents
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22. 4. Resistance Testing
Due to the implications of transmitted (primary) resistance,
A genotypic HIV resistance test is recommended;
Soon after diagnosis.
This ensures that appropriate initial therapy is selected.
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23. 5. Tropism Testing
• Viruses may enter the cell using:
1. CCR5 co-receptor (CCR5-tropic viruses)
2. CXCR4 co-receptor (CXCR4-tropic viruses)
3. Both co-receptors (dual-tropic viruses)
4. Where a mixture of virus population is present, the
term mixed-tropic is used.
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24. 5. Tropism Testing
• Different methods of determining tropism are currently under
evaluation.
• Real time testing; as viral tropism changes as the disease progresses.
• Importance:
If CCR5 inhibitors are to be used, it is essential to determine that the
virus is CCR5-tropic, that is, that there is no significant use of the CXCR4
receptor.
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25. Aims of Drug Therapy
1. Treating or preventing opportunistic complications
2. Alleviating HIV-related symptoms
3. Reducing the HIV viral load
4. Reducing the potential consequences of co-morbidities
5. Restoring immune function
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26. Goals of Therapy
• The goals of therapy in HIV-positive individuals are to:
1. Improve the quality and duration of life;
2. Prevent deterioration of immune function and/or
restore immune status;
3. Treat and/or prevent opportunistic infections;
4. Relieve symptoms.
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27. Anti-Retroviral Therapy
General Principles:
1. A combination of 3 anti-retrovirals should usually be prescribed to
i. increase efficacy and
ii. reduce the development of drug-resistant virus.
2. Wherever possible, a regimen should contain at least one drug that
penetrates CNS and confers protection against HIV-related infections.
3. Treatment strategies should be adopted keeping in mind the potential
cross resistance and future therapy options.
4. Given the crucial importance of a high level of adherence to these
therapies, the regimen adopted should be tailored to suit the daily
lifestyle.
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28. Anti-Retroviral Therapy
• When to start therapy?
when CD4 count drops below 350cells/mm3
• Therapy Strategies:
3 NRTIs
2 NRTIs + 1 NNRTI
2 NRTIs + Boosted PI
‘Boosted PI’ refers to a combination of one PI combined with a low dose
(usually 100–200mg OD or BD) of ritonavir*, another PI.
* Ritonavir ↑ C max & t½, by inhibiting cytochrome P450
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29. Resistance to Anti-Retrovirals
• The aim of initial therapy is to
oachieve viral load suppression in the plasma to levels below the
detection limits accompanied by an elevation in CD4 count.
• Suppression over many years is usually possible, viral rebound
may occur and is often accompanied by the development of
resistance to one or more agents in the combination.
• Resistance test is performed which will help to identify the
oresistant agents
oextent to which such resistance may cause cross-resistance to other
available drugs
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30. Resistance to Anti-Retrovirals
• A second-line regimen is then constructed, wherever possible utilizing
a new class of drug to which the individual has not previously been
exposed.
ADRs:
• Anti-retrovirals, particularly the PIs and NNRTIs, are CYP450 inhibitors
thus exhibit a wide range of interactions, especially with drugs that
are metabolized by this enzyme system leading to severe toxicity.
• E.g., Cushing's syndrome by concomitant use of budesonide inhaler or
nasal spray with a PI.
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31. Classification of Anti-Retrovirals
Anti-Retrovirals
NRTIs
Lamivudine
NNRTIs
Delavirdine
PIs
Squinavir
Entry
Inhibitors
Fusion
Inhibitors
Enfuvirtide
CCR5
Antagonist
Maraviroc
Integrase
Inhibitor
Raltegravir
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33. Class MOA Drug Dose ADRs
NRTIs
(Nucleoside Reverse
Transcriptase
Inhibitors)
They are phosphorylated
intracellularly and then inhibit
reverse transcriptase by acting
as a false substrate.
Lamivudine
150 mg P.O.
BID
Anemia
Lactic Acidosis
NNRTIs
(Non-Nucleoside
Reverse
Transcriptase
Inhibitors)
Inhibit reverse transcriptase by
binding to its active site. No
phosphorylation is req. They
can act on cell-free virions as
well as infected cells.
Delavirdine
400 mg P.O.
TID
Well tolerated
Mild Rash
PIs
(Protease Inhibitors)
Bind to protease enzyme and
prevents maturation of the
newly produced virions so that
they remain non infectious.
Squinavir 600 mg P.O.
TID
Prolonged QC
interval
Raised LFTs
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34. Class MOA Drug Dose ADRs
Fusion
Inhibitor
Block the structural
rearrangement of HIV-1 gp41 &
stops the fusion of viral cell
membrane with the target cell
membrane, preventing its entry
into the cell.
Enfuvirtide 90mg P.O.
BID
Injection site
reactions
Eosinophilia
CCR5
Antagonist
Selectively bind to the human
chemokine receptor CCR5,
preventing CCR5-tropic HIV-1
from entering cells.
Maraviroc
150mg BID
(if g/w significant
enzyme inhibitors)
300mg BID
(if not g/w significant
inhibitors)
Raised creatine
kinase
Constipation
Integrase
Inhibitor
Bind to the integrase enzyme,
thus blocking the integration of
viral DNA into host DNA.
Raltegravir 400mg P.O.
BID
Insomnia
Raised LFTs
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35. Treating Opportunistic Infections
Infection Drug
PCP Clindamycin or
Co-trimoxazole
CMV Cidofovir
MAI Rifabutin or
Azithromycin
Herpes zoster /
Herpes simplex
Acyclovir
Oral Candidiasis Nystatin
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36. Impact of HAART on opportunistic infections
• Decreased incidence of opportunistic infections.
• HAART has resulted in reduction in
 vast majority of opportunistic infections
 mortality rates
 hospital admissions
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37. Considerations
All infected people should be:
1. Treated as individuals
2. Given appropriate information to enable them
• To participate in healthcare decision making process
• Adhere to regimen
3. Given appropriate advice regarding prevention
4. Monitored regularly to detect
• treatment failure
• non-adherence
• drug toxicity
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38. Pharmacist Role
The pharmaceutical care needs for HIV+ individuals are:
P = Poly-pharmacy
A = ADRs
N = New Drugs
D = Drug Interactions
A = Adherence
*They are prescribed large number of drugs (up to 12 tabs/caps per day)
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