HIV I Flashcards
64% of new HIV infections every year occur in ___.
64% of new HIV infections every year occur in Sub-Saharan Africa
~70% of new infections of HIV in the US in 2016 were attributed to ___.
~70% of new infections of HIV in the US in 2016 were attributed to male-male sexual contact.
The highest single-exposure risk for contracting HIV is contact via ___. The second is contact via ___.
The highest single-exposure risk for contracting HIV is contact via blood transfusion. The second is contact via vertical transfer (mother to child).
The primary viral factor which affects transmission is ___.
The primary viral factor which affects transmission is the level of virus in the HIV infected individual
Host factors which affect transmission
- 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
Most often, the transmitted HIV is . . .
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
When is antiretroviral post-exposure prophylaxis most effective?
Within the first few days of infection, before HIV has a chance to multiply locally
Pathway of HIV infection and dissemination
HIV serology studies
Symptoms of the early viremic phase of HIV
- malaise,
- fever,
- rash,
- lymphadenopathy,
- oral ulcers,
- diarrhea
Acute phase of HIV infection is defined as . . .
. . . 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
Generations of HIV detection
- 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
Recommended HIV testing algorithm
HIV “window” period
when virus is present in the blood, but seroconversion has not yet occurred
It is very difficult to diagnose HIV before ___-post infection. If tests come back negative but HIV is still suspected, ___.
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.
Natural progression of HIV
Acute HIV infection may be generally characterized by . . .
Acute HIV infection may be generally characterized by a mononucleosis like illness that occurs within weeks after infection
Untreated individuals with low viral “set points” progress ___, while untreated individuals with high viral “set points” progress ___.
Untreated individuals with low viral “set points” progress more slowly, while untreated individuals with high viral “set points” progress more rapidly.
As the level of CD4+ T cells drops below ___, individuals are at increased risk for opportunistic infections.
As the level of CD4+ T cells drops below 500, individuals are at increased risk for opportunistic infections.
Gut mucosal CD4 T cells in HIV
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.
Ways in which HIV chronically stimulates the immune system to create CCR5 fodder
- 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
Major groups of antiretrovirals for HIV
- HIV protease inhibitors
- Reverse transcriptase inhibitors
- Integrase inhibitors
- Entry inhibitors
Cobicistat
Inhibits the hepatic p450 enzyme which metabolizes many antiretrovirals
Drug-resistance in HIV. . .
. . . develops rapidly when a single antiretroviral is used
General principles of antiretroviral therapy
- 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
Approximately ___% of all DNA transcripts produced contain an error due to the lack of proof reading ability by reverse transcriptase
Approximately 50% of all DNA transcripts produced contain an error due to the lack of proof reading ability by reverse transcriptase
__% of newly infected individuals are unaware of their disease for years before diagnosed.
15% of newly infected individuals are unaware of their disease for years before diagnosed.
The “Berlin” patient
- 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
___ with provirus are not susceptible to ART.
Resting memory T cells with provirus are not susceptible to ART.
Major anatomical reservoires of HIV provirus
- Lymph nodes
- Thymus
- MALT
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?
Impaired viral fusion via gp120 due to mutation in CCR5
Atypical lymphoctes, characteristic of EBV, CMV, HIV
Not infected, but highly, highly activated CD8+ T cells
___, ___, and ___ are clinically indistinguishable in early stages.
EBV, HIV, and CMV are clinically indistinguishable in early stages.
Innate immune mediator timecourse
Ring enhancing lesions
The lighter-centered one is fluid filled. The borders are lining inflammatory cells.
Patients with positive IgG are ___ at risk for toxoplasa
Patients with positive IgG are not at risk for toxoplasa
Ring enhancing lesions on an HIV patient’s radiograph is usually . . .
. . . toxoplasma or B cell lymphoma
CNS disease in HIV
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?
Immune reconstitution inflammatory syndrome (IRIS)
If CD4 is <200, prophylactic ___ is recommended to prevent ____.
If CD4 is <200, prophylactic bactrum is recommended to prevent toxoplasmosis and pneuocystis jirovecii.
