HIV lecture

Question 1

First case of HIV was?

Answer 1

1981 traced back 1959

Question 2

Virus isolated HIV1 was in 1983, and confirmed cause

of AIDS?

Answer 2

1984

Question 3

HIV2 was isolated in?

Answer 3

1986

Question 4

Chimpanze is HIV? Sooty Mangabey is HIV?

Answer 4

HIV1 – Chimpanze

HIV2 – Sooty Mangabey

Question 5

HIV belongs to which family?

Answer 5

Belongs to lentivirus subgroup of retrovirus family

Question 6

What does the HIV virus infect?

Answer 6

Viruses infects white blood cells (lymphocytes and monocytes)

Question 7

What is the entry port for HIV?

Answer 7

CD4 and CCR5 are the entry port

Question 8

HIV-2 is ___% similar to HIV-1

Answer 8

HIV-2 is 55% similar to HIV-1

Question 9

HIV-2 is?

Answer 9

• Prominent cause of AIDS in parts of West Africa and India
  – Has appeared in the U.S.
• Distinct mechanisms of transmission compared to HIV-1

Question 10

HIV attacks variety of cell types. Most critical are?

Answer 10

Helper T-cells and macrophages.

– Attached to CD4 surface receptor

Question 11

What happens after HIV entry?

Answer 11

1) After entry, DNA copies of RNA genome produced using reverse transcriptase viral enzyme
2) DNA copy integrates and hides on host chromosome (Lysogeny)
3) In activated cells virus leaves cell genome and kills cell (Lytic cycle)
4) Releases additional viruses to infect other cells
5) Eventually immune system becomes too impaired to respond

Question 12

HIV is spread primarily by:

Answer 12

Transference of cells and fluids when having sex with a person who has HIV. All unprotected sex with someone who has HIV contains some risk.
– Unprotected receptive sex is riskier (3.0%) than unprotected insertive sex (0.25%).
– Unprotected anal sex (5%) is riskier than unprotected vaginal sex (3%)

Question 13

Transmission of HIV

Answer 13

1) Having multiple sex partners or the presence of other sexually transmitted diseases (STDs) can increase the risk of infection during sex. Unprotected oral sex can also be a risk for HIV transmission, but it is a much lower risk than anal or vaginal sex.
2) Sharing needles, syringes, rinse water, or other equipment used to prepare illicit drugs for injection.
3) Being born to an infected mother—HIV can be passed from mother to child during pregnancy, birth, or breast- feeding.

Question 14

Less common modes of transmission include

Answer 14

1) Being “stuck” with an HIV-contaminated needle
2) Receiving blood transfusions
3) Being bitten by a person with HIV
4) Contact between broken skin, wounds, or mucous membranes
5) There is an extremely remote chance that HIV could be transmitted during “French” or deep, open-mouth kissing.

Question 15

HIV Transmission

It is not spread by

Answer 15

Air or water.
Insects, including mosquitoes.
Saliva, tears, or sweat.
Casual contact like shaking hands or sharing dishes.
Closed-mouth or “social” kissing.

Question 16

HIV Symptoms

Answer 16

– Appear after incubation period of 6 days- 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 (Lymph adenopathy syndrome (LAS))
– Immunodeficiency symptoms include fever, weight loss, fatigue and diarrhea (Referred to as AIDS-related complex (ARC))

Question 17

Destruction of immune system Helper T-cells by HIV can occur via multiple mechanisms

Answer 17

– Lysis following HIV replication
* Can’t account for complete devastation that results from disease
– Attack by HIV-specific cytotoxic CD8+ T lymphocytes
* Lymphocytes will attack and lyse infected cells
– Natural killer cells
* Play a role in cell destruction Lysis following HIV replication
– In nearly 100% of all cases immune system slowly loses ground to virus
– Peripheral CD4+ count steadily falls to nearly 50 cells/μl/year
* Symptoms usually appear when count falls below 200 cells/μl
* Reactivation of latent diseases occur when count falls below 50 cells/ μl.

Question 18

Epidemiology of HIV

Answer 18

1) Unprotected sexual intercourse major factor in spread
* Men who have sex with men, followed by women and minorities.
* Survey indicates before arrival of AIDS 33% to 40% of MSM had more than 500 lifetime partners
* By 1984 two thirds were infected; of those one third had AIDS
2) 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
3) Third most important mode of transmission is mother to infant
* One in 10 pregnant HIV-positive women will miscarry – Oflive-borninfants,15%-40%willdevelopAIDS
 Breast-feeding carries significant risk of mother-infant transmission

Question 19

Epidemiology of HIV

Answer 19

1) Unprotected sexual intercourse major factor in spread
* Men who have sex with men, followed by women and minorities.
* Survey indicates before arrival of AIDS 33% to 40% of MSM had more than 500 lifetime partners
* By 1984 two thirds were infected; of those one third had AIDS
2) 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
3) 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

Question 20

Persons at increased risk for HIV

Answer 20

1) Injected drug users who have shared needles
2) Persons who received blood transfusions or pooled blood products between 1978 and 1985
3) Sexually promiscuous men and women (prostitutes, drug abusers, and homosexual/bisexual men)
4) People w/history of hepatitis B, syphilis, gonorrhea, or other sexually transmitted diseases that may be markers for unprotected sexual intercourse w/mult. partners
5)

Question 21

Persons at increased risk for HIV

Answer 21

1) Injected drug users who have shared needles
2) Persons who received blood transfusions or pooled blood products between 1978 and 1985
3) Sexually promiscuous men and women (prostitutes, drug abusers, and homosexual/bisexual men)
4) People w/history of hepatitis B, syphilis, gonorrhea, or other sexually transmitted diseases that may be markers for unprotected sexual intercourse w/mult. partners
5) People who have had blood or sexual exposure to any of the people listed

Question 22

HIV prevention and treatment

Answer 22

– No approved vaccine and 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
* Viruses in dried blood or pus may be more difficult to inactivate
– 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

Question 23

HIV Treatment

Answer 23

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
1) Nucleoside reverse transcriptase inhibitors: Zidovudine (AZT), stavudine (D4T) and lamivudine (3TC)
2) Non-nucleoside reverse transcriptase inhibitors: Nevirapine, efavirenz and delavirdine

Question 24

Protease inhibitors

Answer 24

• 6 in use

 Act late in HIV replication to prevent packaging of viral proteins

Question 25

Protease inhibitors

Answer 25

• 6 in use

* Act late in HIV replication to prevent packaging of viral proteins

Question 26

HAART

Answer 26

• 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

Question 27

HIV vaccine prospects

Answer 27

– Currently no approved vaccines
– In theory vaccine could be used in two ways:
1) Prevention vaccine: Immunize uninfected individuals against disease
2) Therapeutic vaccine: Boost immunity of those already infected
– Successful vaccine must
1) Produce both mucosal and blood stream immunity
2) Get around HIV variability and stimulate cellular and humoral immunity

Question 28

HIV vaccine prospects: Attenuated agent must not

Answer 28

1) Be capable of turning into disease-causing strain
2) Be oncogenic
3) Stimulate an autoimmune response
4) Must not 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

Question 29

Kaposi’s Sarcoma

Answer 29

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 times higher than period before HIV
* So common among AIDS patients became AIDS-defining condition

Question 30

Kaposi’s Sarcoma

Answer 30

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 times higher than period before HIV
* So common among AIDS patients became AIDS-defining condition
– 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 2 dramatic changes that result in tumor formation
– Cells assume spindle shape and proliferate
– Extensive formation of new blood vessels occurs

Question 31

B-Lymphocytic Tumors of the Brain

Answer 31

–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

Question 32

Cervical and Anal Carcinoma

Answer 32

– Cancer of uterine cervix in women and of anus in women and homosexual men strongly associated with human papillomavirus (HPV) types 16 and 18
– HPV transmitted during sexual activity
* Virus infects cervical and anal epithelium
* Appears to cause increased replication of cells via blocking of cellular gene responsible for controlling cell growth
* HPV replication increases with decline of host immunity

Question 33

Pneumocystosis Symptoms

Answer 33

– 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 – This can be fatal

Question 34

Pneumocystosis

1) Causative agent
2) Pathogenesis

Answer 34

1) Causative agent
– 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
2) 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
* Interferes with free passage of oxygen

Question 35

Pneumocystosis prevention and Treatment

Answer 35

– 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
* Or until achieve sustained rise in CD4+ T-cell above 200 cells/μl

Question 36

Toxoplasmosis Causative agent

Answer 36

Causative agent:
– Toxoplasma gondii
– Banana-shaped protozoan
– Worldwide distribution
– Infects most warm-blooded animals
* Including household pets and domestic farm animals
– Definitive host is cat or other feline
* Organism reproduces in cat intestinal lining
* Offspring shed in feces
– Cyst form of organism can remain viable for months or years

Question 37

Toxoplasmosis Symptoms

Answer 37

– Immunologically normal
* Acquired from eating raw or undercooked meat or exposure to cat feces
* Most infections asymptomatic
* Those with symptoms usually display symptoms like those of mononucleosis
– Sore throat, fever, enlarged lymph nodes and spleen
– Symptoms subside over weeks or months and do not require treatment
– Rarely life-threatening illness develops due to heart or CNS involvement

Question 38

Toxoplasmosis Symptoms in unborn children

Answer 38

– Unborn children
* Disease of unborn results from almost half of maternal infections that occur during pregnancy
* Fetal disease during first trimester least common but most severe
* Often results in miscarriage
* Babies born live may have severe birth defects
* Later may develop seizures or manifest mental retardation
– 2/3 cases occur in last trimester
– Effects are usually less severe
* Retinitis can be big problem
* Less common are seizures and mental retardation

Question 39

Toxoplasmosis Symptoms in Immunodeficient patients

Answer 39

1) Commonly life threatening
2) Brain involvement in form of encephalitis in more than 50% of cases
– Manifested by
 Confusion
 Weakness
 Impaired coordination
 Seizures
 Stiff neck
 Paralysis
 Coma

Question 40

Cytomegalovirus Disease causative agents

Answer 40

– Cytomegalovirus (CMV)
– Enveloped, double-stranded DNA virus
* Looks like other herpes viruses
– Cells infected by the virus are two or more times the size of uninfected cells
– Envelope is acquired as virion buds through Golgi apparatus membrane
– CMV can lyse infected cell and produce active infection or can become latent and later reactivated

Question 41

Cytomegalovirus Disease Symptoms

Answer 41

– Follow pattern similar to toxoplasmosis
– Acute infections in immunocompetent patients usually asymptomatic
* Adolescents and young adults may develop illness resembling mononucleosis
– Severe damage can occur to fetus if mother develops illness during pregnancy
* Congenital cytomegalic inclusion disease
– Characterized by jaundice, large liver, anemia, eye inflammation and birth defects

Question 42

Cytomegalovirus Disease Symptoms

Answer 42

– Blindness most feared complication of illness in immunodeficient individuals
– Other symptoms include
  * Fever
  * Loss of appetite
  * Painful joints and muscles
  * Rapid, difficult breathing
  * Ulcerations of the gastrointestinal tract with bleeding
  * Lethargy and paralysis
  * Dementia
  * Coma and death

Question 43

Cytomegalovirus Disease Prevention and Treatment

Answer 43

– No approved vaccine
– Use of condoms shown to reduce risk of sexual transmission
– Immunocompromised should avoid day care centers and should wash hands if exposed to saliva, urine and feces
– Ganciclovir decreases incidence of retinitis by 50% in HIV patients
– Ganciclovir implants delay progression to blindness
– Combination drug therapy with ganciclovir and foscarnet reduce severity of CMV disease
* Both medications have serious side effects
– Ganciclovir- bone marrow suppression
– Foscarnet- kidney impairment

Question 44

Mycobacterial Diseases Causative agent

Answer 44

– Mycobacterium avium complex (MAC) caused by
M. avium and M. intracellulare
– Growth rate is almost as slow as M. tuberculosis
– Easily distinguished using biochemical testing and nucleic acid probes

Question 45

Mycobacterial Diseases Symptoms

Answer 45

– Immunologically normal individuals are generally asymptomatic

• Elderly particularly those with underlying lung disease may develop chronic productive cough and lesions on the lung
• Children sometimes develop enlarged lymph nodes on the neck
• Easily treated with surgery to remove
• Immunocompromised have slowly progressing symptoms ranging from chronic productive cough to fever, sweats, weight loss, abdominal pain and diarrhea

Question 46

Mycobacterial Diseases Pathogenesis

Answer 46

– Organisms enter body via inhalation or through gastrointestinal tract
– Phagocytized by macrophages
* Resist destruction by inhibiting acid production in phagosome
– Bloodstream carries organism to other sites in the body
– Intact cellular immunity clears organism
* Disease is localized
– Immunocompromised have widespread disease
– Little or no inflammation is produced
– Clinical effect is slow decline in patient health
* Does not produce quick lethal effect

Question 47

Mycobacterial Diseases Epidemiology

Answer 47

– Widespread in natural surroundings
* Found in water, food, soil and dust
– In U.S. prevalent in Southeast, parts of Pacific Coast
and North Central region
– Some strains are important pathogens in chickens and pigs
– Most common bacterial cause of generalized infection in AIDS patients
– Most infections from environmental sources
* Person-to-person spread uncommon

Question 48

Mycobacterial Diseases Prevention and Treatment

Answer 48

– No effective measures to prevent disease
– Clarithromycin is recommended for HIV patients with low CD4+ cell counts
* If bacteriemia develops patients given combination therapy
– Clarithromycin and ethambutol

Question 49

Mechanisms of Action of Antiviral Drugs
Available antiviral drugs effective specific type of virus
– None eliminate latent virus
Targets include

Answer 49

Targets include
– Viral uncoating
– Nucleoside analogs
– Non-nucleoside polymerase inhibitors
– Non-nucleoside reverse transcriptase inhibitors
– Protease inhibitors
– Neuraminidase inhibitors

Question 50

Viral uncoating

Answer 50

– Drugs include amantadine and rimantadine
– Similar in chemical structure and mechanism of action
* Mode of action is blocking uncoating of influenza virus after it enters cell
– Prevents severity and duration of disease
* Resistance develops frequently and may limit effectiveness of drug

Question 51

Non-nucleoside polymerase inhibitor

Answer 51

– Inhibit activation of viral polymerases by binding to site other than nucleotide binding site
* Example = foscarnet and acyclovir
– Used to treat CMV and HSV

Question 52

Non-nucleoside reverse transcriptase inhibitor

Answer 52

Inhibits activity of reverse transcriptase by binding to site other than nucleotide binding site
* Example = nevirapine, delavirdine, efavirenz
– Used in combination to treat HIV

Question 53

Protease inhibitor

Answer 53

Inhibit HIV encoded enzyme protease
* Enzyme essential for production of viral particles
* Examples = indinavir and ritonavir
– Used in treatment of HIV

Question 54

Neuraminidase inhibitor

Answer 54

Inhibit neuraminidase enzyme of influenza
– Enzyme essential for release of virus
– Examples = zanamivir and oseltamivir
– Zanamivir administered via inhalation
– Oseltamivir administered orally