Sexual Trans Inf - Viral (HIV)

Question 1

HIV - virology

Answer 1

• enveloped
• +ssRNA genome (2 copies) in nucleocapsid
• 2reverse transcriptase pol for each copy
• p24 = major capsid protein
• p17 = major matrix protein
• gp41 = fusion protein
• gp120 = attachment protein

Question 2

HIV - lifecycle:

Answer 2

• attachment via gp120 that binds CD4 (T-lymphs, monocytes, macrophages –>this binding allows for a conformational change that exposes a co-receptor (CCR5 or CXCR4) for binding
• all of gp120 activity allows gp41 to get inserted into the host membrane to allow for fusion of membranes –> allows nucleocapsid to get in
• IN CYTOPLASM - reverse transcription [most error prone of all retrovirus enzymes=rapid evolution] (encoded by pol gene) to make DNA double stranded copy.
• dsDNA moves into the nucleus
• integration of DNA via viral integrase = provirus
• geneome replication and transcription of mRNA and proteins
• viron assembly, budding (USING LIPID RAFTS OF HIV PROTEIN)
• not a fully active, mature virion until protein cleavage. (Viral maturation= viral protease that cleaves the gag and gag-pol viral polyproteins)

Question 3

R5-trophic HIV

Answer 3

• Uses CCR5 as a coreceptor
• Almost always transmitted from person-to-person and predominant early in disease
• Efficiently infects monocytes/macrophages and microglia

Question 4

X4-trophic HIV

Answer 4

• Uses CXCR4 as a coreceptor
• Approximately 40% of patients transition from R5 to X4 viruses during the course of disease.
• This is associated with rapid progression to AIDS.

Question 5

HIV-CCR5 deletion

Answer 5

• Some individuals contain a deletion in the region of the CCR5 gene (32) that affects its binding to gp120.
• Heterozygous deletion = longer asymptomatic period before onset of AIDS.
• Homozygous deletion = No infection with R5-tropic viruses. (But, X4-tropic HIV can infect).

Question 6

HIV - transmission

Answer 6

• sexual - most efficient male to female than female to male; usually heterosexual; usually other STI that have genital lesions increase risk for transmission
• perinatal - 1/4 risk without intervention; most common during birth process; virus CAN cross placenta; can be in breast milk
• exposure to contaminated blood or body fluids-healthcare workers

Question 7

HIV disease progression stages:

Answer 7

• Actue - a lot of viral rep (we can look for RNA or p24 antigen); CD4 levels may dip but are still relatively high
• Chronic - viral RNA and p24 levels drop; antibodies for gp120 made; CD4 T-cell levels decline; generally asymptomatic patients (may have some skin and mucous membrane defects);
• AIDS - CD4 T-cell levels drop below 200; antibody levels drop; viral replication takes off again = systematic immune deficiency

Question 8

Acute phase HIV

Answer 8

• Approximately 3-6 weeks following infection
• Symptoms similar to infectious mononucleosis: Fever; Malaise; Arthralgia; Lymphadenopathy; Sore throat
• Rash (usually faint);
• Burst of viremia
• May not have anti-HIV antibodies at this time
• Following the initial burst of viremia, an immune response is mounted that curtails the levels of virus in the blood.
• a lot of viral rep (we can look for RNA or p24 antigen); CD4 levels may dip but are still relatively high

Question 9

Chronic phase HIV

Answer 9

• A low level viremia is present during this time due to viral replication.
• HIV escape from immune system includes: Antigenic drift of gp120; Inactivation of key elements of the immune response; Cell-to-cell fusion
• Patients often: asymptomatic
• Median time of clinical latency in untreated patients is 10 yrs.

Question 10

HIV - set point

Answer 10

basically the MORE HIV RNA copies in pt blood the faster pt will progress to AIDS
-diagnostic indicator for risk of progression

Question 11

Progression to AIDS - HIV

Answer 11

-Reduction in CD4+ T-cell numbers
Mech for killing: Copius budding; Interference with cellular processes; Other mechanisms
-Reduced ability to fight other microbial infections

Question 12

Mechanisms for CD4 t-cell killing by HIV

Answer 12

Copius budqding- the virus takes so much plasma emmbrane with it during budding that the cell dies
Interference with cellular processes;
Other mechanisms

Question 13

Systematic effect of HIV

Answer 13

• dermatalogic manifestations: seborrheic dermatitis; papular pruritic eruptions; eosinophilic folliculitis
• CNS manifestations: AIDS dimentia complex; distal symmetric polyneuropathy
• Other: WASTING (slim disease) anorexia, malabsorption, cant utilize nutrients

Question 14

Early signs of HIV progression

Answer 14

• oral hairy leukoplakia - Epstein Barr Virus
• oral and vaginal candidiasis - C albicans
• herpes zoster (shingles)
• ngihtsweats
• weight loss

Question 15

Late stage HIV associated infections:

Answer 15

• pneumonia: Pneumocystis carninii; Mycobacterium tuberculosis; Mycobacterium avian
• CMV retinitis: cytomegalovirus
• Neoplasms: Kaposi’s sarcoma (HHV-8); B-cell lymphomas
• Diarrhea: ; Cryptosporidium; Isospora belli

Question 16

HIV detection: (antibodies)

Answer 16

(BEST FOR PAST THE ACUTE INFECTION HIV PATEINT)

• start with ELISA (to detect anti-HIV antibodies)
• if positive use Western Blot to confirm ( to detect anti-HIV antibodies

Question 17

HIV detection: R-PCR:

Answer 17

• to detect viral genome in the blood
• If acute HIV is suspected, CDC guidelines recommend ELISA + nucleic acid test.
• Also used to follow the effectiveness of anti-retroviral therapy.

Question 18

HIV detection: other tests:

Answer 18

-PCR to detect provirus in infected cells
-24 antigen test
-Rapid tests for in-office testing for screening
5 products FDA approved, Results in ~20 minutes
Requires subsequent confirmatory testing.

Question 19

HIV diagnosis recommendations:

Answer 19

• if someone seeks eval and treatemnt for STD HIV test is recommended
• person requesting must be free of coercion
• rapid HIV test should be used if pt is unlikely to return for results
• positive tests for HIV antibody must be confirmed with a supplemental test
• providers must use nucleic acid test and antibody test if acute HIV infection is suspected

Question 20

HIV treatment

Answer 20

• block attachemnt; block fusion; block reverse transcription; block integration; block protein cleavage
• Rapid resistance to monotherapy. Ineffective.
• Highly Active Antiretroviral Therapy (HAART): Combination therapies; Greatly increased the lifespan of HIV infected patients.; Issues – Toxicity, Compliance, Resistance
• Prophylactic treatments for opportunistic infections (depends upon the CD4 count).

Question 21

HIV Entry Inhibitors

Answer 21

• Chemokine coreceptor antagonists
• Bind to the co-receptor and prevent its interaction with gp120.
• Maraviroc is a CCR5 antagonist and is limited to use in patients that possess only R5 tropic HIV R5

Question 22

HIV fusion inhibitors

Answer 22

Bind to gp41 and prevent conformational change needed for fusion of the viral envelope with the cellular plasma membrane.

Question 23

HIV Reverse transcription inibitors

Answer 23

1) Nucleoside Inhibitors: Incorporated into growing DNA chain during provirus synthesis and causes chain termination.
2) Nonnucleoside Inhibitors: Bind to reverse transcriptase and inhibit its activity.

Question 24

HIV Integrase Inhibitor

Answer 24

Blocks the integration of the DNA copy of the viral genome into the cellular genome.
-ex raltegravir

Question 25

HIV Protease Inhibitor

Answer 25

Peptidomimetic inhibitors of the viral protease
Protease inhibition leads to the production of immature, defective HIV particles
-ex) saqunavir

Question 26

HIV Prevention:

Answer 26

-public risk reduced: Public education regarding sexual behavior; Education on sexual transmission
Accidental health care exposure risk reduced: Prophylactic antivirals
-Mother-to-infant spread reduced: Antiviral treatment of mother and child; Refrain from breast feeding; Caesarian section delivery
-No Vaccine Available
-Checking donated blood