AIDS

The acquired immunodeficiency syndrome (AIDS). It caused by the human

immunodeficiency virus (HIV-1). Highly active retroviral therapy (HAART)
with three or more drugs has improved life expectancy to near normal in the
majority of patients receiving it, with an 80% reduction of mortality since its
introduction.

MODES OF TRANSMISSION:

HIV is present in the blood, semen and other body fluids such as breast milk
and saliva .Exposure to infected fluid leads to a risk of infection, which is
dependent on the integrity of the exposed site the type and volume of body fluid
and the viral load. HIV can enter either as free virus or within cells.

CLASSIFICATION OF HIV :

PRIMARY INFECTION:

Primary infection is symptomatic in 70-80% of cases and usually occurs 2-6

weeks after exposure.The major clinical manifestations are:

 Fever with rash

 Pharyngitis with cervical lymphadenopathy
 Myalgia
 Headache.
 Mucosal ulceration
diagnosis is made by detecting HIV-RNA in the serum or by immunoblot assay

ASYMPTOMATIC INFECTION:

This lasts for a variable period, during which the infected individual remains
well with no evidence of disease, except for the possible presence of persistent
generalized lymphadenopathy.

MILDLY SYMPTOMATIC DISEASE:

The majority of patients then develop a variety of problems indicating

impairment of the cellular immune system .

 recurrent oropharyngeal or vaginal candidiasis.

 idiopathic thrombocytopenic purpura.
  weight loss.
 periphrral neuropathy.
PRESENTING PROBLEMS IN HIV INFECTION

MUCOCUTANOUS DISEASE:

Type and severity of rash increases .

SPECIFIC SKIN CONDITIONS

FUNGAL INFECTION

Malassezia furfur → causes xerosis with pruritus sebohric dermatitus

and itchy folliclitic rash.

VIRAL INFECTION

Herpes simplax → affect lips , mouth , skin or anogenital area

BACTERIAL AND PARASITIC INFECTION :

S. aureus → celluits , abcess , folliculitis

Bartonella henselae → causes painfull and ulceratied lesions present with

fever , lymphadenopathy and hepato spleenomegally

SPECIFIC ORAL CONDITIONS :

Candidiasis :

Candida albicans → causes white patches on buccal mucosa , tounge ,

pallet , phyranx may also invloved , Oesophagial infections .

GASTRO INTESTINAL DISEASES :

 Pain or swallowing , weight loss and chronic diarrhea are presenting

symptoms or latter stage HIV indicates disease and different sites in GIT

LIVER DISEASE :

 Hepatitis B and C : majority of persons with HIV are more prone to

hepatitis B and C virus exposure
RESPIRATORY DISEASE :

 Pneumocystis
 Mycobacterium tuberculosis
 Bacterial infections → S . Aureus , pseudomonas , H. influenzae

MANAGEMENT OF HIV
Management of HIV involves both treatment of the virus and prevention of
opportunistic infections. The aims of HIV treatment are to:

 reduce the viral load .

 improve the quantity and quality of life without unacceptable drug-related

side-effects or lifestyle alteration

 reduce transmission.
The principle of combining drugs serves to provide additive antiviral activity
with a reduction in the emergence of viral resistance. This is known as highly
active antiretroviral therapy (HAART) and is the cornerstone of management.

1) Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

• Drugs used against retrovirus – HIV
• Useful in prolonging and improving quality of life
• Do not cure the infection
 • Zidovudine (AZT)
• Abacavir (ABC)
• Lamivudine (3TC)
• Didanosine (ddI)
• Zalcitabine (ddC)
• Stavudine (d4T)
• Single stranded viral RNA

Virus directed reverse transcriptase

• Double-stranded viral DNA

Zidovudine:
MOA: Zidovudine triphosphate (Phosphorylated)
• When HIV infects a cell, reverse transcriptase copies the viral single
stranded RNA genome into a double-stranded viral DNA
• The viral DNA is then integrated into the host chromosomal DNA
• Then, host cellular processes start transcribing viral RNA and mRNA to
reproduce the virus
• Regulatory and structural proteins are produced under the direction of
viral mRNA
• Zidovudine inhibits viral reverse.
• Zidovudine prevents infection of new cell by HIV, but not effective on
already infected host chromosomes
Pharmacokinetics:
• The drug is well absorbed after oral administration. If taken with food,
peak levels may be lower. Penetration across the blood-brain barrier is
excellent, then excreted in the urine.
• Adverse effects:
• This drug is very toxic to bone marrow– Anemia and Neutropenia
• G.I disturbances – Nausea, vomiting, abdominal pain
• Myopathy , Myalgia
• Skin rash, Insomnia, Fever, Headaches, Abnormalities of liver
function.
2) Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI):
Nevirapine , Efavirenz , Delavirdine
• MOA:
• Direct inhibitor of reverse transcriptase without intracellular
phosphorylation
 • NNRTIs bind to the Reverse transcriptase and cause its
denaturation
• More potent on HIV-1 than Zidovudine but not HIV-2
• Kinetics:
• Administered Orally.
• Metabolism – Metabolized in the liver and metabolite is excreted in
the urine.
Adverse effects:
• Skin rash
• Fever
• Headaches
• Lethargy.
• If not monitored carefully: Stevens-Johnson syndrome or Toxic
epidermal necrolysis.
• Dose: 200 mg/day
3) Retroviral Protease Inhibitors (PIs):
• Saquinavir , Nelfinavir , Indinavir , Ritonavir , Lopinavir and
Amprenavir
• MOA:
• In last stage of HIV growth cycle viral polyproteins are formed and
then become immature budding particles
• Protease is responsible for cleaving these precursor molecules to
produce the final structural proteins of the mature virion
• PIs bind to these proteins and inhibit formation of structural
proteins
• All given orally
• They are used in combination with Reverse transcriptase inhibitors
• ADRs: G.I disturbances
• Metabolic abnormalities, e.g. insulin resistance, High blood sugar
& Hyperlipidaemia
• Altered distribution of fat (some fat wasting, some fat
accumulation)
• ↑ conc. of liver enzymes
• Renal stones (with Indinavir)

4) HAART (Highly Active Antiretroviral Therapy)

• Aggressive therapy aimed at supressing plasma viral load
• Combination treatment is essential
• Combination treatment → HAART
2 NRTIs + 1 NNRTI (Z+L+Efavirenz) OR
2 NRTIs + 1 or 2 Protease inhibitors (Z+L+lopinavir)