lets know about HIV and AIDS

1. By: Meenakshi Gupta
M.PHARM
Phamacology
Ist sem
PATHOPHYSIOLOGY AND DRUG THERAPY OF
HIV/AIDS AND OPPORTUNISTIC INFECTIONS

2. WHAT IS HIV?
HIV is short for Human Immuno-deficiency Virus. Once infected
with HIV, a person is referred to as HIV positive. However, this
does not necessarily mean that (s)he has symptoms or feels sick.
An HIV positive person can feel and look healthy for a long time
after first becoming infected.
What is AIDS?
AIDS, or Acquired Immuno Deficiency Syndrome, can take
many years to develop. Eventually, the virus kills or impairs more
and more cells in the immune system and the body loses the ability
to fight off common infections, such as diarrhoea or cold. People
with AIDS can die from diseases that are usually not dangerous for
people with healthy immune systems.

3. EPIDEMIOLOGY
Occurs in all ages and ethnic groups
All areas of the country are affected
In some cities, as many as 50% of males are HIV
positive
AIDS is now the second leading cause of death
for all men aged 25-44 years

4. SYMPTOMS
There are basically 5 type of Symptoms as follows :-
1. Pulmonary infections
2. Gastrointestinal infections
3. Neurological and psychiatric involvement
4. Tumors and malignancies
5. Other opportunistic infections
Early infection:
◦ More common to develop a brief flu-like illness 2-4 weeks
after becoming infected. Signs and symptoms may include:
◦ Fever
◦ Headache
◦ Sore throat
◦ Swollen lymph glands
◦ Rash

6. PATHOPHYSIOLOGY

7. • HIV (red) attaches to two cell-surface receptors (the CD4 antigen and a specific
chemokine receptor).
• The virus and cell membrane fuse, and the virion core enters the cell.
• The viral RNA and core proteins are released from the virion core and are then
actively transported to the nucleus.
• The viral RNA genome is converted into double-stranded DNA through an enzyme
unique to viruses, reverse transcriptase (red dot).
• The double-stranded viral DNA moves into the cell nucleus.
• Using a unique viral enzyme called integrase, the viral DNA is integrated into the
cellular DNA.
• Viral RNA is synthesized by the cellular enzyme RNA polymerase II using integrated
viral DNA as a template.
• Two types of RNA transcripts: a. shorter spliced RNA
b. full-length genomic RNA are produced.
• Shorter spliced RNAs are transported to the cytoplasm and used for the production
of several viral proteins that are then modified in the Golgi apparatus of the cell. Full-
length genomic RNAs are transported to the cytoplasm.
• New virion is assembled and then buds off.
• Mature virus is released.

8. MODES OF HIV / AIDS TRANSMISSION
Modes of
transmission
Sexual
contact
Homosexuals
(MSM), &
Heterosexuals
Parenteral
transmissio
n
IVDA,
Hemophiliac
s, accidental
needle
sticks
Vertical
transmissio
n
From mother
to child
during
delivery
(MTCT)

9. Sexual Intercourse - 0.1 to 1% (however frequency
is high causing high rate of infection)
Injectables – 0.5 to 1 %
Parent to child – 30%
Blood/Blood products, tissues, organs- More
than 90%

10. MOTHER-TO-BABY
• Before Birth
• During Birth
• Postpartum
9
Effect of AIDS on Pregnancy
• Infertility
• Repeated abortions
• Prematurity
• Intrauterine growth retardation
• Stillbirths
• Congenital abnormalities
• Embryopathies

11. STAGES OF HIV
Stage 1 - Primary
Stage 2 - Asymptomatic
Stage 3 - Symptomatic
Stage 4 - HIV to AIDS

12. STAGE 1--- PRIMARY
• Short, flu-like illness - occurs one to six weeks after
infection
• no symptoms at all
• Infected person can infect other people

13. STAGE 2 - ASYMPTOMATIC
• Lasts for an average of ten years
• This stage is free from symptoms
• There may be swollen glands
• The level of HIV in the blood drops to very
low levels
• HIV antibodies are detectable in the blood

14. STAGE 3 - SYMPTOMATIC
• The symptoms are mild
• The immune system deteriorates
• emergence of opportunistic infections and
cancers

15. STAGE 4 - HIV  AIDS
• The immune system weakens
• The illnesses become more severe leading
to an AIDS diagnosis

16. TREATMENT
• Restore immune function
• Hasn’t been easy or successful:
• Bone marrow transplant, immunomodulators, transfusions
• Prevent viral replication
• Reverse transcriptase inhibitors (AZT)
• Protease inhibitors eg.Atazanavir,indinavir
• Integrase inhibitiors eg. Elvitegravir,Raltigravir
• Maturation inhibitors eg. Bevirimat
• Fusion inhibitors eg.Enfuvirtide
• Penetration & Uncoating inhibitors eg. Amantadine
• mRNA synthesis inhibitors eg. Ribavarin
• Immunomodulators eg. Interferons
• Others eg. Acyclovir,valaciclovir,idoxuridine,foscarnet

17. ANTIVIRAL DRUG THERAPY

19. HAART
Highly Affective Anti-Retro Viral Therapy:
 Anti-retro viral therapy is recommended if:
Patient is asymptomatic/ symptomatic + CD4
count of <350/µl / any AIDS defining condition /
plasma HIV RNA greater than 100,000 copies/ml
 HAART combines two types of antiretroviral drugs:
Triple cocktail
◦ 2NRTI’S + 1PI or
◦ 2NRTI’S + 1NNRTI

20. REVERSE TRANSCRIPTASE
INHIBITORS (RTI)
• All are 2,3 di-deoxynucleosides. All competitively inhibit DNA dependent RNA
polymerase (reverse transcriptase). All block early events in virus replication. All
are chain terminators (like Acylcovir). Once viral DNA is integrated into host cell
genome, they don’t work.
• Resistance develops due to changes in enzyme. High virus load results in mutants
that are resistant. Cross resistance is not complete so can switch from one inhibitor
to another or use in combination to decrease resistance. BUT don't use two drugs
together with same adverse effect.
• The high rate of RT mutation and resistance to the nucleoside inhibitors led to the
development of non-nucleoside inhibitors
• These drugs are non-competitive inhibitors of reverse transcriptase
• The idea is that mutations in RT leading to resistance to nucleoside inhibitors would
be different than those leading to resistance of the non-nucleoside inhibitors
• Thus, the nucleoside and non-nucleoside RT inhibitors could be used in
combination therapy.

22. ZIDOVUDINE
• Azidothymidine , AZT
• Deoxythymidine analogue
• anti-HIV-1 and HIV-2
• Well absorbed from the gut and distributed to most body tissues and
fluids, including the cerebrospinal fluid.
• Eliminated primarily by renal excretion following glucuronidation in the
liver.
• Decrease the rate of clinical disease progression and prolong survival.
• Treatment HIV-associated dementia and thrombocytopenia.
• Reduce the rate of vertical (mother-to-newborn) transmission of HIV.
• Adverse effect: myelosuppression → anaemia or neutropenia;
gastrointestinal intolerance, headaches, insomnia

23. NON-NUCLEOSIDE REVERSE
TRANSCRIPTASE INHIBITORS
• nevirapine/Viramune (NVP)
• delavirdine/Rescriptor (DLV)
• efavirenz/Sustiva (EFV)
• NNRTI’s are generally hydrophobic molecules that
bind to an allosteric binding site
• Binding to this allosteric site locks the neighboring
substrate-binding site into an inactive conformation.
• However, resistance to NNRTI’s can develop rapidly,
and thus they are used in combination with NRTI’s

24. PROTEASE INHIBITORS
including ritonavir, nelfinavir, saquinavir, indinavir and amprenavir.
Gag and Gag-Pol
gene
Polyproteins,
Immature budding particles
translate
Final structural proteins,
Mature virioncore
protease

25. FUSION OR ENTRY INHIBITORS
• Entry inhibitors prevent HIV from entering human
immune cells.
• There are several key proteins involved in the HIV entry
process:
• CD4, a protein receptor found on the surface of Helper T cells in the
human immune system, also called CD4+ T cells
• gp120, a protein on HIV surface that binds to the CD4 receptor
• CCR5, a second receptor found on the surface of CD4+ cells, called a
chemokine coreceptor
• CXCR4, another chemokine coreceptor found on CD4+ cells
• gp41, a HIV protein, closely associated with gp120, that penetrates the
cell membrane

26. RIBAVIRIN
Active against many DNA/RNA viruses and highly active against influenza A
and B, but is only approved for treating RSV in infants and young children by
aerosol and hepatitis C together with interferon. Clinically Ribavirin was
shown to delay the onset of full-blown AIDS in patients with early symptoms
of HIV infection.
Mechanism of action:
• Ribavirin is a guanine analogue that is phosphorylated by adenosine kinase to its
most active form, ribavirin-triphosphate. This compound inhibits viral RNA-
polymerase preferentially at therapeutic doses by competing with adenosine-
triphosphate and guanine-triphosphate for binding sites at the polymerase, as well
as inhibiting transferases necessary for the addition of guanine.
Toxicity:
• Ribavirin is quite teratogenic in animals - do not give to a patient who is pregnant
(must test and patient must use 2 methods of birth control). May cause
headaches/dizziness - advise health care workers to wear mask when
administering this drug by aerosol. May worsen COPD-like symptoms in some
patients.

27. OPPORTUNISTIC INFECTION
• It is an infection caused by bacterial, viral, fungal or protozoan pathogens that
take advantage of a host with weakened immune system
• Many of pathogen do not cause disease in healthy host that has normal immune
system.
• When the T-cell count drops below 200 cells/cm (14%), there is increased risk of
an AIDS-defining condition occurring.
• AIDS patients often develop opportunistic infections that present with non-
specific symptoms, especially low-grade fevers and weight loss.
• These include infection with Mycobacterium avium-intracellulare and
cytomegalovirus (CMV). CMV can cause colitis .
• CMV retinitis can cause blindness.
• Penicilliosis due to Penicillium marneffei is now the third most common
opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in
HIV-positive individuals within the endemic area of Southeast Asia

29. PNEUMOCYSTIS CARINII
Trimethoprim-sulfamethoxazole15-20mg/Kg/Day
Pentamidineisethionatei.v.4mg/kg/Day

30. TOXOPLASMA GONDII
Trimethoprim-sulfamethoxazole
1 double strength tab. Oral,OD

31. MYCOBACTERIUM INFECTIONS
Azithromycin 1200mg orally once weekly
or
Clarithromycin 500mg Orally twice daily

32. CRYPTOCOCCUS NEOFORMANS
Fluconazole,100-200mg ,orally once daily

33. HERPES SIMPLEX VIRUS
Acyclovir ,200mg five times daily
or
400mg ,three times daily

34. VARICELLA-ZOSTER VIRUS
Acyclovir ,30mg/kg/day for atleast
7 days
Acyclovir 4g/day ,orally

35. CYTOMEGALOVIRUS
Ganciclovir 7.5-10mg/kg/day,i.v.,in 2-3
equally divided dose for 14 days
Maintenance:5-6mg/kg,OD