Is HIV and AIDS the same thing?

HIV “Human Immunodeficiency

Syndrome” A specific type of virus (a

retrovirus) HIV invades the helper T cells to

replicate itself.

AIDS Acquired Immunodeficiency

Syndrome HIV is the virus that causes AIDS Disease limits the body’s ability to

fight infection A person with AIDS has a very

weak immune system

Four Stages of HIV

Stage 1 - Primary Short, flu-like illness - occurs one

to six weeks after infection no symptoms at all Infected person can infect other

people

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

Stage 3 - Symptomatic

The symptoms are mild The immune system deteriorates emergence of opportunistic

infections and cancers

Stage 4 - HIV AIDS

The immune system weakens

The illnesses become more severe leading to an AIDS diagnosis

Opportunistic Infections associated with AIDS

Bacterial Tuberculosis (TB) Strep pneumonia

Viral Kaposi Sarcoma Herpes Influenza (flu)

Opportunistic Infections associated with AIDS

Parasitic Pneumocystis

carinii

Fungal Candida Cryptococcus

Modes of HIV/AIDS Transmission

Through Bodily Fluids

Blood products

Semen

Vaginal fluids

Breast Milk

Through IV Drug Use

Sharing Needles Without sterilization

Increases the chances of contracting HIV

Through Sex

Mother-to-Baby

Before Birth During Birth Postpartum

After the birth

Treatment Options

Antiretroviral Drugs

Nucleoside Reverse Transcriptase inhibitors Zidovudine , Didanosine,

Emtricitabine Non-Nucleoside Transcriptase

inhibitors Nevirapine, Etravirine

Protease inhibitors Ritonavir, Atazanvir

Entry /fusion inibitors:Maraviroc ,Enfuveride vertide

1st effective therapy for HIV was the nucleoside reverse transcriptase inhibitor zidovudine but this drugs or even in combination of drugs from same group were unable to suppress virus for long periods of time and patient eventually dies

Later on the development of other drugs drug from other anti HIV class were also combined such as protease inhibitors indinavir.

This concept of three drug therapy was quickly adapted in to clinical practice this rapidly showed impressive benefit with 60-80% decline in rates of AIDS, death and hospitalization this is called HAART

(highly active antiretroviral therapy.

HIV Life CycleHIV Life Cycle

Step 1: Fusion

Step 2: Transcription

reverse transcriptase

Step 3:Integration

Step 4: Cleavage

Step 5: Packagingand Budding

HIV

Targets for treatment of HIV (anti-retroviral drugsTargets for treatment of HIV (anti-retroviral drugs

Nucleoside Reverse Transcriptase Inhibitors

Zidovudine , Emtricitabine , Didanosine

Are nucleoside & nucleotide analogues

Mechanism of action

Selective reverse transcriptase inhibitors

Acts as competitive substrate inhibitors

Can also be incorporated into growing viral DNA chain

and causes its termination

Zidovudine

Pharmacokinetics Orally effective Penetrates CSF Excreted through kidney

Side effects

Bone marrow depression (leukopenia)

Headache Nausea , anorexia Myopathy , fatigue

Continue Can be used in children in low

doses , during pregnancy & delivery

Emtricitabine

Oral formulation should not be used in a pregnant AIDs patient because it contains a propylene glycol which is a potentially toxic compound for the fetus.

Continue Highly absorbed orally , not

affected by food.

Common adverse effects GIT upset Hyperpigmentation of palms&

soles

Didanosine

Oral bioavailability is reduced by food

Eliminated by the kidney Causes acute pancreatitis as a

side effect & retinal damage & Peripheral neuropathy

Therapeutic effects for all

Increase T cells partially restoring immune system

Reverses AIDS dementia

Non-Nucleoside Transcriptase Inhibitors

Nevirapine ( 1st generstion), Etravirine ( 2nd generation )

Mechanism of action

Bind near the active site of the viral reverse transcriptase to inhibit its activity

( Act as a non-competitive inhibitors of reverse transcriptase enzyme )

Pharmacokinetics

Orally effective Metabolized in liver Excretion through kidney Inducer of hepatic cytochrome

P450

Continue Very effective for prevention of

transmission of infection as a single dose at time of labor and continue as an oral doses for 3 days for the neonates

Side Effects

Hepatotoxicity Skin reaction up to life threating as

Steven-Johnson Syndrome ( mainly with nevirapine)

Diarrhea Headache

Protease Inhibitors

Protease inhibitors

Ritonavir, Atazanvir

Mechanism of action

Block the viral protease enzyme necessary to produce mature virions

( prevent polyprotein cleavage,which is necessary for the maturation of viral cells )

Pharmacokinetics

Atazanavir oral absorption requires an acid environmentExcretion via biliary eliminationEnzyme inhibitors P450

Pharmacokinetics

Ritonavir Should be taken with meals ( its oral bioavailability increases with food )Clearance is mainly via the liverEnzyme inhibitors P450

Side effects for protease inhibitors

Increased bleeding in hemophilic patients

Increased blood sugar level ( worsening of diabetes)

Changes in body fat distribution central obesity, buffalo hump, (gynecomastia)

Dorsocervical fat pad (“buffalo hump’)

Entry Inhibitors Maraviroc Mechanism of action Blocks certain strains of HIV from

binding to chemokine receptor type 5 ( CCR5) thus preventing the virus from entering target cells.

Continue If the patient,s virus is chemokine

receptor type 4 , the drug will not be effective.

Cross CSF Excreted mostly through feces Well tolerated & few side effects

Thank You!