5. 5
Epidemiology
ī§ 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.
ī§ In 2009, HIV infected approximately 33
million people worldwide. Approximately
68% of these cases are in sub-Saharan
6. 6
Epidemiology
ī§ In 2009 alone, approximately 1.8 million
people died from AIDS and 2.6 million
people were newly infected with HIV.
ī§ Most of these infections were acquired
through heterosexual transmission.
ī§ 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.
7. 7
HIV
ī Human Immunodeficiency Virus
ī§ H = Infects only Human beings
ī§ I = Immunodeficiency virus
weakens the immune system and
increases the risk of infection
ī§ V = Virus that attacks the body
8. 8
HIV virus infection
ī The HIV Virus:
ī§ Invades the helper T cells (CD4
cells) in the body of the host
(defense mechanism of a person).
ī§ Is threatening a global epidemic.
ī§ Is preventable & manageable but is
NOT curable.
9. 9
AIDS
ī Acquired Immune Deficiency
Syndrome
ī§ A = Acquired, not inherited
ī§ I = Weakens the Immune system
ī§ D = Creates a Deficiency of CD4+
cells in the immune system
ī§ S = Syndrome, or a group of
illnesses taking place at the same
time
10. 10
HIV and AIDS
ī§ When the immune system becomes
weakened by HIV, the illness
progresses to AIDS
ī§ Some blood tests, symptoms or
certain infections indicate
progression of HIV to AIDS
11. 11
HIV and AIDS
ī§ AIDS Predisposes our body to other
opportunistic infections.
ī§ Opportunistic infections and malignancies that
rarely occur in the absence of severe
immunodeficiency (e.g. Pneumocystis
pneumonia, central nervous system lymphoma).
ī§ 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.
12. 12
Viral Genome
ī§ enveloped virus of the
lentivirus subfamily of
retroviruses.
ī§ Retroviruses transcribe
RNA to DNA.
13. 13
Viral Genome
ī§ Two viral strands of RNA found in core
surrounded by protein outer coat.
ī§ Outer envelope contains a lipid matrix within
which specific viral glycoproteins are
imbedded.
ī§ These knob-like structures responsible for
binding to target cell.
15. 15
Types
īą HIV â1
ī§ Group M- 10 subtypes, 90% of all cases
world wide
ī§ Group O (Now able to be detected with most
routine HIV antibody tests)
īą HIV â 2
ī§ 1% of cases world wide
ī§ Slower progression
ī§ West Africa
ī§ 79 cases in US, but most were African born
16. 16
HIV-1 and HIV-2
ī§ Transmitted through the same routes
ī§ Associated with similar opportunistic
ī§ infections
ī§ HIV-1 is more common worldwide
ī§ HIV-2 is found in West Africa,
Mozambique, and Angola
ī§ HIV-2 is less easily transmitted
ī§ HIV-2 is less pathogenic
ī§ Duration of HIV-2 infection is shorter
17. 17
Overview of Pathophysiology
ī§ HIV destroys bodyâs immune system by
selectively attacking T-4 Lymphocytes,
also macrophages & B cells
ī§ HIV indirectly affects CNS by neurotoxins
produced by the infected macrophages
ī§ As CD4+ count declines, body becomes
more susceptible to opportunistic infections
19. 19
Risk Factors
I. Sexual Practices that promote
Disease Transmission
ī§ Under the influence of drugs
ī§ Multiple partners
ī§ Sores in genital area
20. 20
Risk Factors
II. Exposure to blood/body fluids
ī§ Administration of blood or blood products
ī§ Transplantation of tissue or organs
ī§ 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
21. 21
Other Risk Factors
ī§ Ulcerative STDâs
o Syphilis
o Herpes simplex
o Chancroid
ī§ Non-ulcerative STDâs
o Gonorrhea
o Chlamydia
o Trichomoniasis
24. 24
Primary infection
(Acute HIV)
ī§ Most develop a flu-like illness within a month
or two after the virus enters the body.
ī§ may last for a few weeks.
ī§ Fever , Headache ,Muscle aches and joint pain
ī§ Rash
ī§ Sore throat and painful mouth sores
ī§ Swollen lymph glands, mainly on the neck
ī§ These symptoms can be so mild that you might
not even notice them.
26. 26
Clinical latent infection
(Chronic HIV)
ī§ Person is HIV+ but asymptomatic
ī§ lasts for several years (subclinical)
o viral replication occurring up to 10 billion
virons per day
ī§ Chronic lymphadenopathy
27. 27
Early Symptomatic
Disease
ī§ CD4 counts drop to 500-600 cells/ml
ī§ Symptoms:
o recurrent fever, night sweats,
malaise, headache
ī§ Physical findings:
o lymphadenopathy, spleen enlarged,
rash, weight loss
28. 28
Symptomatic HIV infection
ī§ Fever
ī§ Fatigue
ī§ Swollen lymph nodes â often one of the
first signs of HIV infection
ī§ Diarrhea
ī§ Weight loss
ī§ Oral yeast infection (thrush)
ī§ Shingles (herpes zoster)
29. 29
Progression to AIDS
ī§ Average time between infection and AIDS
was 10 years
ī§ time has increased with new protease
inhibitors
ī§ CD4 count <200/mm
ī§ majority of manifestations due to
opportunistic infections due to
immunosuppression rather than direct
injury by virus
30. 30
Some symptoms of AIDS
ī§ Soaking night sweats
ī§ Recurring fever
ī§ Chronic diarrhea
ī§ Persistent white spots or unusual lesions
on your tongue or in your mouth
ī§ Persistent, unexplained fatigue
ī§ Weight loss
ī§ Skin rashes or bumps
34. 34
Other Complications
ī§ Wasting syndrome.
ī§ Neurological complications. such as
confusion, forgetfulness, depression,
anxiety and difficulty walking and
dementia complex.
ī§ Kidney disease.
37. 37
Laboratory diagnosis
īą Evidence of HIV infection
ī§ Virus isolation
ī§ Measurement of viral nucleic acid
ī§ Detection of viral antigen
ī§ Detection of viral antibody
īą Recognition of immunodeficiency
ī§ CD4+ T cell count
īą Recognition of AIDS related disease
38. 38
Laboratory diagnosis
A. Virus isolation:
ī§ HIV can be cultured from lymphocytes in
peripheral blood.
B. Detection of viral Nucleic Acid :
ī§ By RT-PCR
ī§ Branched-chain DNA
39. 39
Laboratory diagnosis
C. Detection of HIV Antigen
ī§ Detect the presence of HIV in blood
ī§ P24 antigen tests measure one of the
proteins found in HIV
D. Detection of antibody
ī§ measuring antibodies by ELISA.
ī§ Western Blot assay
40. 40
Laboratory diagnosis
īą Window period:
ī§ Early in infection when the blood of an
infected person can contain HIV but antibodies
are not detectable.
īą Seroconversion:
ī§ Development of evidence of antibody
response to a disease.
īą Viral Load:
ī§ The amount of HIV in the blood.
41. 41
Window Period
ī§ A period of 4-6 weeks after HIV
exposure when antibodies to HIV are
not detectable in the blood
ī§ A person at high risk who initially
tests negative should be retested at 3
months to confirm diagnosis
46. 46
Maintain Health
ī§ Baseline & q 6-12 mos.
ī§ CBC
ī§ Chemistries
ī§ Annual Screening
ī§ TB Skin tests/Chest x-ray
ī§ Pregnancy
ī§ Hep A & B to determine need for
immunization; Hep B and/or C co-infection
ī§ Testing for pathogens known to cause
opportunistic infections
ī§ CD4 & Viral load testing (every 3-6 months)
47. 47
Antiretroviral therapy
ī§ There's no cure for HIV/AIDS, but many
different drugs are available to control the
virus called Antiretroviral therapy, or ART.
ī§ Each class of drug blocks the virus in
different ways.
ī§ ART is now recommended for everyone,
regardless of CD4 T cell counts.
ī§ It's recommended to combine three drugs
from two classes to avoid creating drug-
resistant strains of HIV.
48. 48
Initiate & maintain ART
ī§ Viral load is 5000- 10,000
ī§ Evidence of clinical or immunologic
deterioration
ī§ (CD4 counts <500 mm3)
ī§ Viral load > 20,000 even without
evidence of clinical deterioration
49. 49
When to start treatment
ī§ Everyone with HIV infection, regardless of
CD4 T cell count, should be offered antiviral
medication.
ī§ HIV therapy is particularly important for the
following situations:
īŧ severe symptoms.
īŧ Presence of an opportunistic infection.
īŧ CD4 T cell count is under 350.
īŧ Pregnant.
īŧ HIV-related kidney disease.
īŧ Presence of hepatitis B or C.
53. 53
Antiretroviral Agents
īą Reverse Transcriptase Inhibitors
i. Nucleoside reverse transcriptase inhibitors
ī§ (NsRTIs)Incorporate into viral DNA
terminating its construction
ī§ E.g. Lamivudine - Abacavir
ii. Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIâs)
ī§ Action is similar to NRTIâs; bind directly to
reverse transcriptase
ī§ E.g. Nevirapine
56. 56
Antiretroviral Agents
īą Integrase inhibitors
ī§ work by disabling a protein called
integrase, which HIV uses to insert
its genetic material into CD4 T
cells.
ī§ E.g raltegravir
57. 57
Antiretroviral Agents
Regimen
īą All recommended regimens for initial treatment
contain an NNRTI, a ritonavir-boosted PI, or an
INSTI in combination with tenofovir (NtRTI) and
emtricitabine (NRTI).
ī§ The preferred agents are as follows:
1. NRTI/NtRTI combination: Tenofovir and
emtricitabine
2. PIs: Atazanavir/ritonavir
3. NNRTI: Efavirenz
4. INSTI: Raltegravir
58. 58
Evaluation of treatment
ī§ Criteria
o HIV RNA (viral load) in blood
o Count of T cells
o Appropriate clinical response
ī§ Treatment Failure
o viral load with low T-cell count
o Clinical deterioration
o New opportunistic infections
59. 59
Strategies to maximize
benefits/minimize toxicities
1) Alternating therapies
2) Combination therapy:
ī§ Demonstrated more beneficial than
monotherapy
i. Decreased emergence of resistance
ii. Decreased risk of toxicity
60. 60
Adherence
īą Major cause of resistance is sub-therapeutic
dosing :
ī§ failure to take prescribed dose
ī§ failure to take prescribed dose at prescribed
intervals
ī§ interactions with other drugs that decrease
blood levels of ART
62. 62
HIV infected Pregnant
Female
ī§ Standard antiretroviral therapy should
be used in the HIV infected pregnant
female
ī§ Possible risk of premature delivery
(highest in non-treated individuals)
64. 64
Prevention of HIV
Infections
I. Vaccines
ī§ Pre-clinical work in animals is promising
II. Education, Counseling & Behavior mod.
III. Free needles for IV drug users
IV. Improved blood supply
ī§ Greatly decreased risk for hemophiliacs
V. Screening and treating pregnant women
65. 65
Prevent Opportunistic
Infection
īą Pneumocystosis jirovecii Pneumonia (80%) at least
once
ī§ Prophylaxis when CD4+ count < 200mmÂŗ
o Dapsone
o TMP-SMX
īą Mycobacterium avium complex (60%) found to
have active infection at death
ī§ Prophylaxis when CD4+ count < 50 mmÂŗ
ī§ +PPD with ø CMâs of active Tb
o Prophylaxis with INH-9 mos
o Pyridoxine to prevent peripheral neuropathy