hiv

1. HIV/AIDS
Management
Dr. Sameh Ahmad Muhamad abdelghany
Lecturer Of Clinical Pharmacology
Mansura Faculty of medicine

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 Describe clinical characteristics of
HIV?AIDS
 Identify Causative agent-risky factors
 Review appropriate drug therapy
Objectives

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AIDS
INTRODUCTION
Cause
RISK FACTORS
Diagnosis
Treatment & Prevention
CONTENTS

4. INTRODUCTION

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Epidemiology
 Since the first cases of AIDS were identified
in 1981, close to 30 million people have died
as a result of HIV infection. This makes AIDS
one of the most destructive epidemics in
recorded history. The epidemic remains
extremely dynamic, and no country in the
world is unaffected.
 In 2009, HIV infected approximately 33
million people worldwide. Approximately
68% of these cases are in sub-Saharan

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Epidemiology
 In 2009 alone, approximately 1.8 million
people died from AIDS and 2.6 million
people were newly infected with HIV.
 Most of these infections were acquired
through heterosexual transmission.
 As of December 2009, women accounted for
52% of all people living with HIV worldwide.
Persons aged 15 to 24 years accounted for
approximately 40% of new HIV infections
worldwide.

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HIV
 Human Immunodeficiency Virus
 H = Infects only Human beings
 I = Immunodeficiency virus
weakens the immune system and
increases the risk of infection
 V = Virus that attacks the body

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HIV virus infection
 The HIV Virus:
 Invades the helper T cells (CD4
cells) in the body of the host
(defense mechanism of a person).
 Is threatening a global epidemic.
 Is preventable & manageable but is
NOT curable.

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AIDS
 Acquired Immune Deficiency
Syndrome
 A = Acquired, not inherited
 I = Weakens the Immune system
 D = Creates a Deficiency of CD4+
cells in the immune system
 S = Syndrome, or a group of
illnesses taking place at the same
time

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HIV and AIDS
 When the immune system becomes
weakened by HIV, the illness
progresses to AIDS
 Some blood tests, symptoms or
certain infections indicate
progression of HIV to AIDS

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HIV and AIDS
 AIDS Predisposes our body to other
opportunistic infections.
 Opportunistic infections and malignancies that
rarely occur in the absence of severe
immunodeficiency (e.g. Pneumocystis
pneumonia, central nervous system lymphoma).
 Persons with positive HIV serology who have
ever had a CD4 lymphocyte count below 200
cells/mcL or a CD4 lymphocyte percentage
below 14% are considered to have AIDS.

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Viral Genome
 enveloped virus of the
lentivirus subfamily of
retroviruses.
 Retroviruses transcribe
RNA to DNA.

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Viral Genome
 Two viral strands of RNA found in core
surrounded by protein outer coat.
 Outer envelope contains a lipid matrix within
which specific viral glycoproteins are
imbedded.
 These knob-like structures responsible for
binding to target cell.

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Viral Genome

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Types
 HIV –1
 Group M- 10 subtypes, 90% of all cases
world wide
 Group O (Now able to be detected with most
routine HIV antibody tests)
 HIV – 2
 1% of cases world wide
 Slower progression
 West Africa
 79 cases in US, but most were African born

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HIV-1 and HIV-2
 Transmitted through the same routes
 Associated with similar opportunistic
 infections
 HIV-1 is more common worldwide
 HIV-2 is found in West Africa,
Mozambique, and Angola
 HIV-2 is less easily transmitted
 HIV-2 is less pathogenic
 Duration of HIV-2 infection is shorter

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Overview of Pathophysiology
 HIV destroys body’s immune system by
selectively attacking T-4 Lymphocytes,
also macrophages & B cells
 HIV indirectly affects CNS by neurotoxins
produced by the infected macrophages
 As CD4+ count declines, body becomes
more susceptible to opportunistic infections

18. RISK FACTORS

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Risk Factors
I. Sexual Practices that promote
Disease Transmission
 Under the influence of drugs
 Multiple partners
 Sores in genital area

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Risk Factors
II. Exposure to blood/body fluids
 Administration of blood or blood products
 Transplantation of tissue or organs
 Implantation of infected semen
III. Use of injected drugs(drug abuse)
IV. Occupational exposure
o Accidental needle stick
V. HIV-infected mothers to infants during
pregnancy, delivery, or breastfeeding

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Other Risk Factors
 Ulcerative STD’s
o Syphilis
o Herpes simplex
o Chancroid
 Non-ulcerative STD’s
o Gonorrhea
o Chlamydia
o Trichomoniasis

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23. DIAGNOSIS

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Primary infection
(Acute HIV)
 Most develop a flu-like illness within a month
or two after the virus enters the body.
 may last for a few weeks.
 Fever , Headache ,Muscle aches and joint pain
 Rash
 Sore throat and painful mouth sores
 Swollen lymph glands, mainly on the neck
 These symptoms can be so mild that you might
not even notice them.

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Symptoms of Acute HIV

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Clinical latent infection
(Chronic HIV)
 Person is HIV+ but asymptomatic
 lasts for several years (subclinical)
o viral replication occurring up to 10 billion
virons per day
 Chronic lymphadenopathy

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Early Symptomatic
Disease
 CD4 counts drop to 500-600 cells/ml
 Symptoms:
o recurrent fever, night sweats,
malaise, headache
 Physical findings:
o lymphadenopathy, spleen enlarged,
rash, weight loss

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Symptomatic HIV infection
 Fever
 Fatigue
 Swollen lymph nodes — often one of the
first signs of HIV infection
 Diarrhea
 Weight loss
 Oral yeast infection (thrush)
 Shingles (herpes zoster)

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Progression to AIDS
 Average time between infection and AIDS
was 10 years
 time has increased with new protease
inhibitors
 CD4 count <200/mm
 majority of manifestations due to
opportunistic infections due to
immunosuppression rather than direct
injury by virus

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Some symptoms of AIDS
 Soaking night sweats
 Recurring fever
 Chronic diarrhea
 Persistent white spots or unusual lesions
on your tongue or in your mouth
 Persistent, unexplained fatigue
 Weight loss
 Skin rashes or bumps

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Symptoms of AIDS

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Complications
I- Infections common to HIV/AIDS
 Pneumocystic jirovecii pneumonia
 Tuberculosis
 Cytomegalovirus.
 Candidiasis.
 Cryptococcal meningitis.
 Toxoplasmosis.
 Cryptosporidiosis.

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Complications
II. Cancers common to HIV/AIDS
 Kaposi's sarcoma
 Lymphoma.

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Other Complications
 Wasting syndrome.
 Neurological complications. such as
confusion, forgetfulness, depression,
anxiety and difficulty walking and
dementia complex.
 Kidney disease.

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Common HIV related infections

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HIV Complications

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Laboratory diagnosis
 Evidence of HIV infection
 Virus isolation
 Measurement of viral nucleic acid
 Detection of viral antigen
 Detection of viral antibody
 Recognition of immunodeficiency
 CD4+ T cell count
 Recognition of AIDS related disease

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Laboratory diagnosis
A. Virus isolation:
 HIV can be cultured from lymphocytes in
peripheral blood.
B. Detection of viral Nucleic Acid :
 By RT-PCR
 Branched-chain DNA

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Laboratory diagnosis
C. Detection of HIV Antigen
 Detect the presence of HIV in blood
 P24 antigen tests measure one of the
proteins found in HIV
D. Detection of antibody
 measuring antibodies by ELISA.
 Western Blot assay

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Laboratory diagnosis
 Window period:
 Early in infection when the blood of an
infected person can contain HIV but antibodies
are not detectable.
 Seroconversion:
 Development of evidence of antibody
response to a disease.
 Viral Load:
 The amount of HIV in the blood.

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Window Period
 A period of 4-6 weeks after HIV
exposure when antibodies to HIV are
not detectable in the blood
 A person at high risk who initially
tests negative should be retested at 3
months to confirm diagnosis

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Window Period
 Seropositive:
 detectable antibodies to HIV in the
serum
 person becomes infectious within 2
weeks of exposure

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Laboratory diagnosis
E. CD4:CD8 cell count:
 Absolute number of CD4+ cell and
ratio of helper cell to inducer cell are
abnormally low.

44. TREATMENT

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Outcome Management
 Maintain Health
 Initiate & maintain Antiretroviral
Rx
 Prevent infection

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Maintain Health
 Baseline & q 6-12 mos.
 CBC
 Chemistries
 Annual Screening
 TB Skin tests/Chest x-ray
 Pregnancy
 Hep A & B to determine need for
immunization; Hep B and/or C co-infection
 Testing for pathogens known to cause
opportunistic infections
 CD4 & Viral load testing (every 3-6 months)

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Antiretroviral therapy
 There's no cure for HIV/AIDS, but many
different drugs are available to control the
virus called Antiretroviral therapy, or ART.
 Each class of drug blocks the virus in
different ways.
 ART is now recommended for everyone,
regardless of CD4 T cell counts.
 It's recommended to combine three drugs
from two classes to avoid creating drug-
resistant strains of HIV.

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Initiate & maintain ART
 Viral load is 5000- 10,000
 Evidence of clinical or immunologic
deterioration
 (CD4 counts <500 mm3)
 Viral load > 20,000 even without
evidence of clinical deterioration

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When to start treatment
 Everyone with HIV infection, regardless of
CD4 T cell count, should be offered antiviral
medication.
 HIV therapy is particularly important for the
following situations:
 severe symptoms.
 Presence of an opportunistic infection.
 CD4 T cell count is under 350.
 Pregnant.
 HIV-related kidney disease.
 Presence of hepatitis B or C.

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Antiretroviral Agents
I. Entry inhibitors
II. Reverse Transcriptase inhibitors
III. Protease inhibitors
IV. Integrase inhibitors

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Antiretroviral Agents

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Antiretroviral Agents
 Entry Inhibitors:
 Prevent HIV from entering healthy
T cells in the body
 enfuvirtide(Fuzeon)

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Antiretroviral Agents
 Reverse Transcriptase Inhibitors
i. Nucleoside reverse transcriptase inhibitors
 (NsRTIs)Incorporate into viral DNA
terminating its construction
 E.g. Lamivudine - Abacavir
ii. Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTI’s)
 Action is similar to NRTI’s; bind directly to
reverse transcriptase
 E.g. Nevirapine

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Antiretroviral Agents
 Reverse Transcriptase Inhibitors
iii. Nucleotide Reverse Transctriptase
Inhibitors (NtRTI’s)
 E.g. Tenofovir

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Antiretroviral Agents
 Protease Inhibitors (PI’s)
o Prevent assembly & release of new
virus particles
o E.g Ritonavir - Saquinavir

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Antiretroviral Agents
 Integrase inhibitors
 work by disabling a protein called
integrase, which HIV uses to insert
its genetic material into CD4 T
cells.
 E.g raltegravir

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Antiretroviral Agents
Regimen
 All recommended regimens for initial treatment
contain an NNRTI, a ritonavir-boosted PI, or an
INSTI in combination with tenofovir (NtRTI) and
emtricitabine (NRTI).
 The preferred agents are as follows:
1. NRTI/NtRTI combination: Tenofovir and
emtricitabine
2. PIs: Atazanavir/ritonavir
3. NNRTI: Efavirenz
4. INSTI: Raltegravir

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Evaluation of treatment
 Criteria
o HIV RNA (viral load) in blood
o Count of T cells
o Appropriate clinical response
 Treatment Failure
o viral load with low T-cell count
o Clinical deterioration
o New opportunistic infections

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Strategies to maximize
benefits/minimize toxicities
1) Alternating therapies
2) Combination therapy:
 Demonstrated more beneficial than
monotherapy
i. Decreased emergence of resistance
ii. Decreased risk of toxicity

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Adherence
 Major cause of resistance is sub-therapeutic
dosing :
 failure to take prescribed dose
 failure to take prescribed dose at prescribed
intervals
 interactions with other drugs that decrease
blood levels of ART

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Adherence
Factors affecting adherence
1. Complex dosing schedules
2. Adverse side effects
3. Unknown cross reactions
4. Cost
5. Access to Care

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HIV infected Pregnant
Female
 Standard antiretroviral therapy should
be used in the HIV infected pregnant
female
 Possible risk of premature delivery
(highest in non-treated individuals)

63. PREVENTION

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Prevention of HIV
Infections
I. Vaccines
 Pre-clinical work in animals is promising
II. Education, Counseling & Behavior mod.
III. Free needles for IV drug users
IV. Improved blood supply
 Greatly decreased risk for hemophiliacs
V. Screening and treating pregnant women

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Prevent Opportunistic
Infection
 Pneumocystosis jirovecii Pneumonia (80%) at least
once
 Prophylaxis when CD4+ count < 200mm³
o Dapsone
o TMP-SMX
 Mycobacterium avium complex (60%) found to
have active infection at death
 Prophylaxis when CD4+ count < 50 mm³
 +PPD with ø CM’s of active Tb
o Prophylaxis with INH-9 mos
o Pyridoxine to prevent peripheral neuropathy

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Prevent Opportunistic
Infection
 Flu & pneumonia vaccine
 Prevention of travelers diarrhea – Cipro
 Safer sex practices
 Food & water safety
 Skin & mucous membrane integrity

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