HIV I

Question 1

64% of new HIV infections every year occur in ___.

Answer 1

64% of new HIV infections every year occur in Sub-Saharan Africa

Question 2

~70% of new infections of HIV in the US in 2016 were attributed to ___.

Answer 2

~70% of new infections of HIV in the US in 2016 were attributed to male-male sexual contact.

Question 3

The highest single-exposure risk for contracting HIV is contact via ___. The second is contact via ___.

Answer 3

The highest single-exposure risk for contracting HIV is contact via blood transfusion. The second is contact via vertical transfer (mother to child).

Question 4

The primary viral factor which affects transmission is ___.

Answer 4

The primary viral factor which affects transmission is the level of virus in the HIV infected individual

Question 5

Host factors which affect transmission

Answer 5

• Complicating additional STIs (which may cause ulceration or otherwise local susceptibillity to infection)
• Type of sexual behavior (anal sex risk > vaginal sex risk > oral sex risk)
• Gender of sexual partners (highest risk M to M, lowest risk W to W)
• CCR5 variants of individuals involved

Question 6

Most often, the transmitted HIV is . . .

Answer 6

Most often, the transmitted HIV is macrophage-tropic HIV (also known as R5 HIV) and this virus preferentially utilizes the CCR5 co-receptor, not the CXCR4 receptor

Question 7

When is antiretroviral post-exposure prophylaxis most effective?

Answer 7

Within the first few days of infection, before HIV has a chance to multiply locally

Question 8

Pathway of HIV infection and dissemination

Answer 8

Question 9

HIV serology studies

Answer 9

Question 10

Symptoms of the early viremic phase of HIV

Answer 10

• malaise,
• fever,
• rash,
• lymphadenopathy,
• oral ulcers,
• diarrhea

Question 11

Acute phase of HIV infection is defined as . . .

Answer 11

. . . the time between the appearance of HIV RNA and before HIV infection is detectable by immunoassays, lasts between 5 and 40 days after RNA appears. Duration depends on s on the generation of immunoassay used for testing

Question 12

Generations of HIV detection

Answer 12

• 1st generation: HIV IgG, high level, earliest ~50 days
• 2nd generation: HIV IgG, low levels, earliest ~35 days
• 3rd generation: HIV IgM, low levels, earliest ~22 days
• 4th generation: HIV-1 p24 antigen, earliest ~15 days
• Nucleic acid tests: HIV-1 RNA, earliest ~10 days

Question 13

Recommended HIV testing algorithm

Answer 13

Question 14

HIV “window” period

Answer 14

when virus is present in the blood, but seroconversion has not yet occurred

Question 15

It is very difficult to diagnose HIV before ___-post infection. If tests come back negative but HIV is still suspected, ___.

Answer 15

It is very difficult to diagnose HIV before 15 days-post infection. If tests come back negative but HIV is still suspected, order a serum HIV RNA assay now and have the patient come back in a few days for another protein assay.

Question 16

Natural progression of HIV

Answer 16

Question 17

Acute HIV infection may be generally characterized by . . .

Answer 17

Acute HIV infection may be generally characterized by a mononucleosis like illness that occurs within weeks after infection

Question 18

Untreated individuals with low viral “set points” progress ___, while untreated individuals with high viral “set points” progress ___.

Answer 18

Untreated individuals with low viral “set points” progress more slowly, while untreated individuals with high viral “set points” progress more rapidly.

Question 19

As the level of CD4+ T cells drops below ___, individuals are at increased risk for opportunistic infections.

Answer 19

As the level of CD4+ T cells drops below 500, individuals are at increased risk for opportunistic infections.

Question 20

Gut mucosal CD4 T cells in HIV

Answer 20

Acute infection is associated with massive depletion of mucosal CD4+ T cells that are typically enriched with cells co-expressing CCR5. This gut mucosal CD4+ T cell depletion can lead to infection and inflammation of the entire bowel.

Question 21

Ways in which HIV chronically stimulates the immune system to create CCR5 fodder

Answer 21

• Direct effects of HIV as a ligand for toll like receptors on plasmacytoid dendritic cells leading to production of interferon-α
• microbial translocation across the gut and activation of TLR4 leading to the production of pro-inflammatory cytokines
• co-infection with viruses (eg CMV) leading to CMV specific T cell activation
• reduced ratio of Thelper-17 and regulatory T cells, especially in the gastrointestinal tract

Question 22

Major groups of antiretrovirals for HIV

Answer 22

• HIV protease inhibitors
• Reverse transcriptase inhibitors
• Integrase inhibitors
• Entry inhibitors

Question 23

Cobicistat

Answer 23

Inhibits the hepatic p450 enzyme which metabolizes many antiretrovirals

Question 24

Drug-resistance in HIV. . .

Answer 24

. . . develops rapidly when a single antiretroviral is used

Question 25

General principles of antiretroviral therapy

Answer 25

* Everyone receives a combination of *at least* two active drugs * Common regimens include: * NRTI plus protease inhibitor * NRTI plus integrase inhibitor * NRTI plus NNRTI * Diagnose as early as possible * Start treatment **at time and location of diagnosis** * Protect people at risk * Respond quckly to new clusters of HIV cases

Question 26

Approximately \_\_\_% of all DNA transcripts produced contain an error due to the lack of proof reading ability by reverse transcriptase

Answer 26

Approximately **50%** of all DNA transcripts produced contain an error due to the lack of proof reading ability by reverse transcriptase

Question 27

\_\_% of newly infected individuals are unaware of their disease for years before diagnosed.

Answer 27

**15%** of newly infected individuals are unaware of their disease for years before diagnosed.

Question 28

The "Berlin" patient

Answer 28

* Only case known where an individual was cured of HIV * HIV positive man that contracted AML * He required a bone marrow transplant, relapsed, and was given a second transplant from a donor homozygous for the CCR5 delta 32 mutation * This patient remains with no detectable HIV RNA after 9 years on no ART

Question 29

\_\_\_ with provirus are not susceptible to ART.

Answer 29

**Resting memory T cells** with provirus are not susceptible to ART.

Question 30

Major anatomical reservoires of HIV provirus

Answer 30

* Lymph nodes * Thymus * MALT

Question 31

A 30-year-old man has receptive anal intercourse with his HIV positive partner for over ten years without infection. He is found to have a homozygous mutation on his CD4 cells. What is likely to explain the mechanism of his apparent immunity to HIV?

Answer 31

Impaired viral fusion via gp120 due to mutation in CCR5

Question 32

Answer 32

Atypical lymphoctes, characteristic of EBV, CMV, HIV Not infected, but highly, highly activated CD8⁺ T cells

Question 33

\_\_\_, \_\_\_, and ___ are clinically indistinguishable in early stages.

Answer 33

**EBV**, **HIV**, and **CMV** are clinically indistinguishable in early stages.

Question 34

Innate immune mediator timecourse

Answer 34

Question 35

Answer 35

Ring enhancing lesions The lighter-centered one is fluid filled. The borders are lining inflammatory cells.

Question 36

Patients with positive IgG are ___ at risk for toxoplasa

Answer 36

Patients with positive IgG are **not** at risk for toxoplasa

Question 37

Ring enhancing lesions on an HIV patient's radiograph is usually . . .

Answer 37

. . . **toxoplasma or B cell lymphoma**

Question 38

CNS disease in HIV

Answer 38

Question 39

A patient with a CD4 count of 82 starts on HAART and returns a month later with acutely worsening symptoms but a CD4 count of 250. What is the likely diagnosis?

Answer 39

Immune reconstitution inflammatory syndrome (IRIS)

Question 40

If CD4 is \<200, prophylactic ___ is recommended to prevent \_\_\_\_.

Answer 40

If CD4 is \<200, prophylactic **bactrum** is recommended to prevent **toxoplasmosis and pneuocystis jirovecii**.