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HIV Disease and Complications of
Immunodeficiency
Chapter 29
HIV Disease
Symptoms
Appear after incubation period of 6 days to 6 weeks
Usually consist of fever, headache, sore throat, muscle
aches, enlarged lymph nodes and generalized rash
Some develop CNS symptoms
Range from moodiness and to seizures and paralysis
Symptoms constitute acute retroviral syndrome (ARS)
Typically subside in 6 weeks
Acute illness followed by asymptomatic period
Period may end with persistent enlargement of lymph nodes
Lymphadenopathy syndrome (LAS)
Immunodeficiency symptoms include fever, weight loss,
fatigue and diarrhea
Referred to as AIDS-related complex (ARC)
HIV Disease
Causative agent
In U.S and most other parts of the world disease caused
by human immunodeficiency virus type 1 (HIV-1)
Belongs to lentivirus subgroup of retrovirus family
HIV-2 is similar in structure to HIV-1 but is antigenically
distinct
Prominent cause of AIDS in parts of West Africa and India
Has appeared in the U.S.
Transmission is less efficient than HIV-1
Disease progresses slower
HIV Disease
Pathogenesis
HIV Disease
HIV attacks a variety of cell types
Most critical are helper T cells
Viral gp120 attaches to CD4 cell surface receptor
Viral gp41 induces membrane fusion by interacting
with chemokine cell surface receptor (CCR)
After entry, DNA copies of RNA genome produced
using reverse transcriptase viral enzyme
DNA copy integrates and hides on host chromosome
In activated cells virus leaves cell genome and kills
cell
Releases additional viruses to infect other cells
Macrophages have CD4 receptors
Infected macrophages are not killed but are impaired
Eventually immune system becomes too impaired to
HIV Disease
Pathogenesis
HIV Disease
Destruction of immune system helper T
cells by HIV can occur via multiple
mechanisms
Lysis following HIV replication
Attack by HIV-specific cytotoxic CD8+ T
lymphocytes
CTL kill HIV-infected T cells
Antibody-dependent cellular cytotoxicity
Antibodies bind to gp120 and gp41 viral
glycoproteins on infected T cells, facilitating the
killing of those cells
Autoimmune process
Fusion of infected and uninfected cells
Facilitated by gp120 and gp41 on infected
cells and CD4 and CCR on uninfected cells
Apoptosis
HIV Disease
Pathogenesis
In nearly 80% of all cases immune system slowly loses
ground to virus
Peripheral CD4+ count steadily falls to nearly 50 cell /µl
Symptoms usually appear when count falls below 200 cells/µl
Atypical progression of disease occurs in roughly 10%
of infected individuals
Disease progresses rapidly to AIDS within a few months
Another 5% - 10% do not experience a fall in CD4+ cells
Maintain high levels of antibodies and CD8+ cells
Disease progresses slowly
May be AIDS-free for 20 years
Epidemiology
HIV Disease
Indiscriminate sexual intercourse major factor in spread
Promiscuous homosexual men most common
Survey indicates before arrival of AIDS 33% to 40% of homosexual men
had more than 500 lifetime partners
Next most important mode of transmission is through
blood and blood products
By 1984 over 50% of hemophiliacs in U.S. were infected
10% - 20% of their sexual partners were HIV positive
Today, blood transmission is usually I.V. drug use (needle-sharing)
Third most important mode of transmission is mother to
infant
One in 10 pregnant HIV-positive women will miscarry
Of live-born infants, 15% - 40% will develop AIDS
Breast feeding carries significant risk of mother-infant transmission
HIV Disease
Prevention and Treatment
No approved vaccine
Most people infected are unaware
Virus on surfaces can be inactivated with
commercially available disinfectants and heat at 56°C
for more that 30 minutes
Knowledge of transmission greatest tool for control
Use of condoms not 100% effective but have been
shown to decrease transmission
Avoidance of practices that favor HIV transmission
HIV Disease
Prevention and Treatment
Treatment directed at “cocktails” of drugs
Combination of reverse transcriptase
inhibitors and protease inhibitors
HAART = highly active antiretroviral therapy
Reverse transcriptase inhibitors fall into
two categories
Nucleoside reverse transcriptase inhibitors
Zidovudine (AZT), stavudine (D4T) and
lamivudine (3TC)
Non-nucleoside reverse transcriptase
inhibitors
Nevirapine, efavirenz and delavirdine
HIV Disease
Prevention and Treatment
Highly-Active Anti-Retroviral Therapy
Protease inhibitors
6 in use
Act late in HIV replication to prevent packaging of
viral proteins
HAART does not cure AIDS
Viremia becomes undetectable in approximately
50% of cases
Will reappear in absence of treatment
Many strains fail to respond to HAART due to
resistance
HIV Disease
HIV vaccine prospects
Currently no approved vaccines
In theory, vaccine could be used in two ways
Prevention vaccine
Immunize uninfected individuals against disease
Therapeutic vaccine
Boost immunity of those already infected
Successful vaccine must
produce both mucosal and blood stream
immunity
get around HIV variability and stimulate cellular
and humoral immunity
HIV Disease
HIV vaccine prospects
Attenuated agent must not:
Be capable of turning into disease-causing strain
Be oncogenic
Stimulate an autoimmune response
Cause production of “enhancing” antibodies that could aid in the
passage of HIV into the body’s cells
Finally, vaccine should induce neutralizing antibodies
against free virions and prevent direct spread of HIV
from cell to cell
Vaccine trial in humans has been undertaken for at least
10 experimental vaccines
All have failed and prospects do not look favorable
Kaposi’s Sarcoma
Unusual tumor arising from
blood or lymphatic vessels in
multiple locations
Common in men of
Mediterranean and Eastern
European descent
Not as a sign of immunodeficiency
Tumor began to appear in young
men with HIV
2000 time higher than period before
HIV
So common among AIDS patients
became AIDS-defining condition
Kaposi’s Sarcoma
Human herpesvirus-8 (HHV-8) detected in sarcomas
Virus infects endothelial cells that line blood and
lymphatic vessels
Persists mostly in latent form
Presence of virus associate with two dramatic changes
that result in tumor formation:
Cells assume spindle shape and proliferate
Extensive formation of new blood vessels occurs
B-Lymphocytic Tumors of the Brain
B-cell lymphomas 60 to 100 times more common in
AIDS patients compared to general public
Intense, sustained replication of lymphoid cells is
constant feature of HIV
Lymph node enlargement reflects proliferation of
lymphoid cells in response to high level unregulated
cytokine release
Replication of T cells occurs to replace those destroyed by
HIV
Epstein-Barr virus plays roll in B-cell lymphomas
associated with AIDS
Lymphomas rarely occur in brain except with AIDS
patients
Pneumocystosis
Symptoms
Typically begins slowly with gradually increasing
shortness of breath and rapid breathing
Fever is usually slight or absent
50% of patients have non-productive cough
Skin and mucous membranes becomes dusky
Due to poor oxygenation of blood
Causative agentPneumocystosis
- Pneumocystis carinii
Tiny fungus belonging to phylum
Ascomycota
Formerly considered a protozoan
Differs from many fungi in cell wall
components
Consequently resistant to many fungal
medications
Pathogenesis
Spores of organism are inhaled into lung
Attach to alveolar walls
Alveoli fill with fluid, mononuclear cells and
organisms
Alveolar walls become thickened and
scarred
Pneumocystosis
Epidemiology
Widespread among animals including dogs, cats,
horses and rodents
Serological testing indicates almost all children are
infected by age two and a half
Infection is asymptomatic and generally eliminated in a year
Source of transmission in humans is unknown
Most cases of pneumocystosis occur in immunocompromised
Epidemics among hospitalized malnourished infants
and elderly nursing home residents suggest airborne
spread
Pneumocystosis
Prevention and Treatment
Disease used to occur in four-fifths of AIDS patients
Was leading cause of death
Disease largely preventable with regular doses of
trimethoprim-sulfamethoxazole (TxS)
Among the best medication for treating disease
along with oxygen support
Reduced mortality rate from nearly 100% to
30%
After treatment patient must receive preventive
medication indefinitely until rise in CD4+ T cells above
200 cells/μl
Other Common Opportunistic
Infections of AIDS
Toxoplasmosis (Toxoplasma gondii)
Herpesviruses
Herpes simplex viruses 1&2
Cytomegalovirus
Mycobacterium avis (TB-like disease)