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Term 5: Infectious Disease > 5/29- Retroviruses > Flashcards

5/29- Retroviruses Flashcards

1
Q

What makes something a retrovirus?

A

Virus uses reverse transcriptase to convert viral RNA to DNA.

This allows insertion of viral DNA into the host DNA and establishes, latent, life-long infection

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2
Q

Clinically significant retroviruses?

A
  • HTLV-1 and 2
  • HIV-1 and 2
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3
Q

HIV Life Cycle

A
  • Viral surface binds host cell receptors (CD4)
  • Fusion of viral and host membranes and IC insertion
  • Uncoating
  • Reverse transcriptase transcribes RNA into dsDNA
  • Integration of viral DNA into host genome
  • Transcription/lation into viral mRNA/proteins
  • Assembly, budding/release
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4
Q

Cellular Receptors for HIV

A

- CCR5*

- CXCR4

*Homozygous deletions of CCR5 protect from HIV infxns

(heterozygotes have relative protection w/ slower progression; 20% in N. Europe)

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5
Q

Question:

What is the prevalence of HIV in the US?

In Sub-saharan Africa?

A
  • US: 0.5-1%
  • SS Africa: ~5%

Although not homogeneous distribution; certain regions or portions of the population have much higher rates

  • NYC (MSM): 14%
  • South Africa: 17%
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6
Q

What is considered high prevalence for HIV/AIDS in a population?

A

> 1%

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7
Q

Modes of transmission of HIV (stat breakdown)

A
  • MSM: 62%
  • Heterosexual contact: 28% (female 18%, male 10%)
  • Injection drug use: 8% (males 5%, females 3%)
  • MSM and IV drug use: 3%
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8
Q

Race/ethnicity distribution of HIV/AIDS?

A
  • Mostly black (males 42%, females 63%)
  • White (males 30%, females 17%)
  • Hispanic/Latino (males 23%, females 17%)
  • Others….
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9
Q

Question:

What is the most important factor in the sexual transmission of HIV?

A. Type of sexual encounter

B. HIV infected person’s viral load

C. Presence of sexually transmitted disease (STD) in HIV-infected person

D. Presence of STD in non-HIV infected partner

E. Lack of circumcision

A

Answer:

What is the most important factor in the sexual transmission of HIV?

A. Type of sexual encounter

B. HIV infected person’s viral load

C. Presence of sexually transmitted disease (STD) in HIV-infected person

D. Presence of STD in non-HIV infected partner

E. Lack of circumcision

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10
Q

What factor is directly associated with transmission?

A

Viral load in infected fluid or secretions

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11
Q

Which is infectious free or cell-associated virus?

A

Both

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12
Q

Transmission requires what?

A
  • Contact of infected fluid with mucosa or non-intact skin
  • Inoculation of infected fluid directly into bloodstream (transfusion, IV drug use)

HIV DOES NOT survive well in the environment

NOT transmitted through insect bites

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13
Q

Prevention of sexual transmission of HIV

A
  • Safe sex practices (Abstinence, Be faithful, Condom use)
  • Circumcision
  • Topical microbicides/antivirals
  • Systemic antivirals (treatment of all HIV infected persons)
  • Pre-exposure prophylaxis (PrEP) of those at high risk
  • Post-exposure prophylaxis within 72 hours of exposure to known/suspected HIV infected Intact skin is excellent barrier against HIV transmission
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14
Q

Prevention of HIV transmission through drug use

A

IVDU:

  • Substance use treatment
  • Needle exchange programs for IVDU
  • Recommend safe disposal of needles
  • HIV pre-exposure prophylaxis

Non IVDU:

  • Associated with HIV transmission via increased sexual risky behaviors
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15
Q

What organ may harbor higher levels of the virus?

A

Prostate

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16
Q

Who should get pre-exposure prophylaxis (PrEP)?

A
  • HIV positive sexual partner
  • Recent bacterial STA
  • High number of sex partners
  • Inconsistent/no condom use
  • Commercial sex work
  • High prevalence area
  • HIV positive injecting partners or sharing injection equipment
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17
Q

What is the perinatal transmission rate of untreated HIV?

What are the different methods of transmission/%?

A

Up to 40% in untreated pregnancy/delivery

  • In utero
  • Intrapartum
  • Postpartum: breastfeeding (15-30%)

Most transmission occurs in peripartum period (prolonged rupture of membranes can play a role)

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18
Q

Prevention of perinatal HIV transmission?

A
  • HIV testing for all pregnant women
  • ART treatment for all HIV infected pregnant women
  • Intrapartum AZT for untreated women or with VL > 1000
  • AZT (+/- other ARVs) for infant for 6 weeks
  • Elective C-section prior to rupture of membranes
  • Avoid breastfeeding

(Different guidelines for developing countries, e.g. exclusive breastfeeding recommended for first 6 mo)

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19
Q

Prevention of nosocomial HIV transmission?

A
  • Percutaneous exposure (0.3% risk)
  • Mucous membrane exposure (0.1% risk)

Risk increases with volume of blood, depth of injury, VL

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20
Q

Treatment for nosocomial HIV transmission?

A

Post-exposure prophylaxis

  • Start ASAP!
  • 4 weeks of antiretrovirals
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21
Q

HIV-1 pathogenesis (pic)

A

Latently infected CD4 cells and the long lived cells are why HIV infection cannot be eliminated; they perpetuate the existence of HIV as they divide even in the absence of active viral replication

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22
Q

Natural history of untreated HIV infection (chart)

A
  • High THC count in primary infection, drop through clinical latency down to death
  • Low initial viral load followed by spike with acute HIV syndrome (wide dissemination of virus and seeding of lymphoid organs)
  • Viral load spike followed by drop in latency until quick rise going from constitutional symptoms, opportunistic diseases and death
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23
Q

Acute retrovirus syndrome symptoms

A

Alone or in combo:

  • Fever (96%)
  • Rash (70%)
  • Lymphadenopathy (70%)
  • Pharyngitis (70%)
  • Diarrhea (30%)
  • Headaches (30%)
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24
Q

When does acute retrovirus syndrome occur (timeframe)?

A

1-4 weeks after infection

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25
Q

What is the viral load (relatively) during acute retrovirus syndrome?

A

High! Massive destruction of CD4 population (gut associated) and transient low CD4 count

26
Q

At what point in pathogenesis is infectivity highest?

A

During acute retrovirus syndrome

27
Q

What are the 2 most important markers for infection of HIV?

A
  • CD4 count
  • Viral load
28
Q

Characteristics of chronic HIV infxn (symptoms, timeframe)?

A
  • Subclinical
  • Persistent immune activation and dysfunction
  • Lasts ~10 years (3-12)
  • Viral load and CD4 predict progression
29
Q

Definition of AIDS

A

(1993)

  • CD4 < 200
  • Opportunistic infections (OI)
  • Opportunistic cancers
  • HIV associated conditions

—Wasting syndrome: weight los, diarrhea, fever

—HIV-related damage to specific organ systems, e.g. HIV encephalopathy

30
Q

Stages of HIV infection?

A
  • Acute (< 4 weeks)
  • Early (4 weeks- 6 months)
  • Chronic infection
31
Q

Methods of HIV diagnosis? Which apply to which stages?

A

Early stage of infection, can use:

  • PCR for viral RNA
  • ELISA for p24 or HIV-1 specific Ab
  • Western blots for HIV-specific Ab; p31

Chronic infection, can only use:

  • ELISA for HIV-1 specific Ab
  • Western blot for HIV-1 specific Ab; p31
32
Q

Recommended lab HIV testing (flowchart)

A
33
Q

What does ELISA detect in terms of HIV Ab detection?

A

Abs against HIV 1 and HiV 2 (IgG and IgM) with high sensitivity and specificty

Use samples of blood, serum, saliva (typ serum)

Rapid ELISA with blood/saliva ONLY detects IgG

34
Q

Confirmatory test following + ELISA test? What does it detect?

A

Multispot (differentiates HIV 1/2)

Detects IgG

35
Q

Antigen detection of what for HIV diagnosis?

A

p24 (4th gen ELISA)

36
Q

What nucleic acid amplification tests (NAAT) can be used for diagnosis of HIV 1?

A

RNA (GenProbe)

DNA in PBMC (newborns)

37
Q

HIV testing assays and window periods (chart)

A
38
Q

Where is HIV 2 mostly found?

A

West Africa (rare in the US)

39
Q

Comparative transmission and disease progression of HIV 2 compared to HIV 1?

A

HIV 2 is slightly harder to transmit and has slower disease progression

40
Q

Does ELISA screening detect HIV 1, 2, or both?

A

Detects antibodies for both

41
Q

Does multispot detect HIV 1,2, or both?

A

Differentiates between 1 and 2

42
Q

Does HIV viral load detect HIV 1, 2, or both?

A

HIV 1 viral load does not see HIV 2

43
Q

Where is HTLV I found?

A

Southwestern Japan

Caribbean basin

44
Q

Where is HTLV II found?

A

IVDU in N America, Europe, and some native American populations

45
Q

Transmission of HTLV

A
  • Sexual contact (male to female most common)
  • Breastfeeding (via infected lymphocytes)
  • Transfusion of cellular blood components
  • Plasma by itself does not transmit HTLV!
46
Q

Diseases associated with HTLV I

A
  • Adult T cell leukemia/lymphoma
  • HTLV I-associated myelpathy
47
Q

Diseases associated with HTLV II?

A
  • None identified so far
48
Q

What is the lifetime risk of adult T cell leukemia/lymphoma with HTLV I?

A

Lifetime risk: 1-4%

(Latency 30-50 years)

49
Q

When is HTLV I most commonly acquired?

A

Childhood

50
Q

Clinical presentation of Adult T cell leukemia/lymphoma?

A
  • Skin lesions: papules and nodules
  • Lymphadenopathy
  • Hypercalcemia, lytic bone lesions, visceral involvement
  • Immunosuppression/opportunistic diseases
  • Peripheral smear: lymphocytes with convoluted nuclei (flower cells)
  • Poor outcome
51
Q

What is this?

A

Person with HTLV 1- associated Cutaneous Lymphoma

52
Q

What does HTLV stand for?

A

Human T-cell Lymphotropic Virus 1

53
Q

Symptoms of HTLV1-Associated Cutaneous Lymphoma

A
  • Violaceous papules and nodules on face and ear
54
Q

Viral characteristics of HTLV1?

A

dsRNA type C virus

(first retrovirus associated with malignancy in humans)

55
Q

Where is endemic region for HTLV1?

A
  • Japan (up to 33% in some pops) and Caribbean
  • (lesser) Central and S America and Africa
56
Q

What percentage of people with HTLV infection will develop adult T cell lymphoma?

A

2-4%

57
Q

What is the lifetime risk of HTLV I-Associated Myelopathy?

Typical onset?

Male vs. female?

A
  • Lifetime risk < 1%
  • Typical onset: 4th decade
  • 2x more females than males
58
Q

Symptoms of HTLV-1 Associated Myelopathy?

A

Chronic worsening demyelination:

  • Gait disturbance
  • Weakness
  • Stiffness of legs
  • Spasticity
  • Incontinence

NO cognitive changes, no CN involvement

59
Q

Prevention of HTLV I/II infection?

A

Avoid practices that could transfer lymphocytes:

  • Organ donation
  • Blood donation
  • Breastfeeding

Use condoms

60
Q

Question:

Pt had unprotected sexual encounter with a partner of unknown HIV status 10 days ago. She is having fever and is worried about HIV. Which test should be ordered at this point in time?

A. HIV blood ELISA

B. HIV saliva rapid test

C. HIV Western Blot

D. HIV viral load

E. None

A

Answer:

Pt had unprotected sexual encounter with a partner of unknown HIV status 10 days ago. She is having fever and is worried about HIV. Which test should be ordered at this point in time?

A. HIV blood ELISA

B. HIV saliva rapid test

C. HIV Western Blot

D. HIV viral load

E. None

61
Q

What is Tropical spastic paresis?

A

Another name for HTLV-1 Associated Myelopathy

Term 5: Infectious Disease (18 decks)

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