Immunologic Diseases I (AIDS/HIV) Flashcards
(68 cards)
1
Q
What is HIV?
A
- The human immunodeficiency virus (HIV) was first isolated in 1983 and was retrospectively identified as the cause of acquired immunodeficiency syndrome
- HIV is a non-transforming retrovirus (Retroviridae family) of the lentivirus subfamily
2
Q
What are the types of HIV?
A
- Two main subtypes, HIV-1 and HIV-2, based on genetic and antigenic differences, and many strains of each
- HIV-1 being more common (overall) particularly in sub-Saharan Africa, while HIV-2 is more prevalent in West Africa and associated with slower disease course
3
Q
An estimated _____________ people across the globe are newly infected with HIV annually
A
2.7 million
4
Q
Bythe end of 2019, approximately _________ people were estimated to be living with HIV
A
38 million
5
Q
What is the breakdown of HIV by continent?
A
- Eastern and southern Africa ~54%
- Asiaandthe Pacific ~15%
- Western andcentral Africa ~13%
- Western and Central Europe and North America ~6%
6
Q
Approximately __________ people in the U.S. are living with HIV today
A
1.2 million
7
Q
What is more likely to have HIV…
males or females
young, middle, or old
A
males
middle (25-44)
8
Q
True/false
Today, male-to-male sexual contact remains the largest single risk factor with greater proportion of cases arising in blacks/African Americans, Hispanics/Latinos, females, and heterosexuals.
A
True
9
Q
How is HIV transmitted?
A
- Blood, semen, breast milk, and vaginal secretions are the main fluids that have been shown to be associated with transmission of the virus. HIV can also be found in tears, saliva, cerebrospinal fluid, amniotic fluid, and urine
- Transmission of HIV is by exchange of infected bodily fluids predominantly through intimate sexual contact and by parenteral means (Sharing needles and blood transfusions, organ transplants etc.)
- HIV infection can occur through oropharyngeal, cervical, vaginal, and gastrointestinal mucosal surfaces, even in the absence of mucosal disruption
- Infection is particularly aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation
10
Q
The most common method of sexual transmission of HIV in the United States is anal intercourse in men who have sex with men (MSM), in whom the risk of HIV infection is ___________ higher than in other men and in women.
A
40 times
11
Q
Heterosexual transmission (male to female or female to male) is the second most common form of transmission of HIV in the United States but accounts for ______ of the world’s HIV infections
A
80%
12
Q
Transmission of HIV from _________ is the third largest group affected in the United States
A
sharing needles
12
Q
The risk of transmission of HIV from a blood transfusion is estimated to be less than _______ because of current screening measures
A
1 in 1 million
13
Q
Transmission of HIV by oral fluids is…
A
somewhat controversial and rarely documented
14
Q
The presence of ____________ may predispose an individual to oral transmission of HIV
A
erosions, ulcerations, and hemorrhagic inflammatory pathoses
15
Q
What is the structure of HIV?
A
16
Q
What are the three main keye antigenic components (genes) of HIV?
A
- Gag
— processed to matrix and other core proteins that determine retrovial core
— p24 (CA), p17 (MA), p7 (NC) - Pol
— reverse transcriptase, RNase H and integrase functions
— p66/51 (RT), p32 (IN), p11 (PR) - Env
— envelope protein, resides in lipid layer; determine viral tropism
— gp120 (V3 loop), gp41
17
Q
HIV particles are seen at _________ magnification in this electron micrograph
A
medium
Note the central core and the outer envelope
18
Q
What is the cell cycle of HIV?
A
Entry -> Replication -> Release
19
Q
How does entry into the cell by HIV work?
A
- HIV primarily infects cells with CD4 cell-surface receptor molecules (CD4+ T helper lymphocytes mainly) at the site of HIV entry
- Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected delivering HIV to underlying T cells, ultimately resulting in dissemination to lymphoid organs
- The virus uses CD4+ cells to gain entry by fusion with a susceptible cell membrane or by endocytosis (with the help of co-receptors CXCR4 and CCR5)
20
Q
The probability of infection of a cell with HIV depends on both…
A
- the number of infective HIV virions in the body fluid which contacts the host
- the number of cells with appropriate CD4 receptors available at the site of contact
21
Q
How does replication of HIV in a cell work?
A
- Once within the cell, the viral particle uncoats from its spherical envelope to release its RNA
- The enzyme product of the pol gene, a reverse transcriptase that is bound to the HIV RNA, synthesizes linear double-stranded cDNA that is the template for HIV integrase
- It is this HIV proviral DNA which is then inserted into the host cell genomic DNA by the integrase enzyme of the HIV
22
Q
How does release of HIV from the cell work?
A
- Just before the budding process, HIV protease cleaves Gag proteins into their functional form which get assembled at the inner part of the host cell membrane, and virions then begin to bud off
— Nucleocapsid (NC) protein interacts with the RNA within the capsid
— Capsid (CA) protein surrounds the RNA of HIV
— Matrix (MA) protein surrounds the capsid and lies just beneath the viral envelope - The cells HIV selects for replication are soon “swell and burst” by caspase-3 mediated apoptosis (~5%), the remaining >95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection
23
Q
Thespectrum of HIV disease changes as CD4+ cell count _________
A
declines
24
_____________ is the transition from the point of viral infection to when antibodies of the virus become present in the blood (circulating antibodies)
Seroconversion
25
What are the CDC stages of HIV infection in adults and adolescents?
- Stage 1 (Immediately after HIV exposure and may last for years)
- Stage 2 (Progressive immunosuppression and early symptomatic disease)
- Stage 3 (AIDS; variety of immunosuppression-related diseases)
26
What is stage 1 of HIV infection according to the CDC?
- Immediately after HIV exposure and may last for years
- Laboratory confirmation of HIV infection, no AIDS defining conditions and CD4+ T lymphocyte count of ≥500 cells/μL or CD4+ Tl ymphocyte percentage of total lymphocytes of
≥29
27
What is stage 2 of HIV infection according to the CDC?
- Progressive immunosuppression and early symptomatic disease
- Laboratory confirmation of HIV infection, no AIDS defining condition, and laboratory confirmation of HIV infection and CD4+ T lymphocyte count of 200–499 cells/μL or CD4+ T lymphocyte percentage of total lymphocytes of 14–28
28
What is stage 3 of HIV infection according to the CDC?
- AIDS; variety of immunosuppression-related diseases
- Laboratory confirmation of HIV infection and CD4+ T lymphocyte count is<200 cells/μL or CD4+ T lymphocyte percentage of total lymphocytes is <14 or documentation of an AIDS defining condition. Documentation of an AIDS-defining condition supersedes a CD4+T lymphocyte count of ≥ 200cells/μL and a CD4+ T lymphocyte percentage of total lymphocytes of ≥14
29
What are some specific symptoms of stage 2 HIV?
Enlarged lymphnodes, nightsweats, weightloss, oral candidiasis, fever, malaise, & diarrhea
30
What are some specific symptoms of stage 3 HIV?
Opportunistic infections predominate; then malignancies, wasting syndrome, & aprogressive form of dementia & other neurological deficits (AIDS-dementia complex)
31
During the first 2 to 6 weeks after initial infection with HIV, ~70% of patients develop an _____________ marked by viremia that may last 10 to 14 days (sometimes up to 4 weeks). Others may not manifest this symptom complex.
acute flulike syndrome
32
Symptomatic persons of stage 1 HIV often develop mononucleosis-like symptoms such as...
lymphadenopathy, fever, pharyngitis, weakness, diarrhea, nausea, vomiting, myalgia, headache, weight loss, and a skin rash (roseola-like or urticarial)
| Only an estimated 20% of symptomatic persons seek medical attention
33
What are the signs/symptoms of stage I HIV?
- acute flulike syndrome marked by viremia (only in some people)
--- lymphadenopathy, fever, pharyngitis, weakness, diarrhea, nausea, vomiting, myalgia, headache, weight loss, and a skin rash
- A concomitant transient fall in CD4+ cells occurs along with high titers of plasma HIV, but patients do not develop evidence of immunosuppression
- This is usually followed by developing antibodies (anti-gag, anti-gp120, anti-p24) between weeks 6 and 12. A few may take 6 months or longer to achieve seroconversion particularly in patients without acute symptoms
34
the ________ the acute infection lasts the earlier patients develop AIDS
longer
35
During the first ___________ after initial infection with HIV, ~70% of patients develop an acute flulike syndrome marked by viremia
2 to 6 weeks
36
Developing antibodies (anti-gag, anti-gp120, anti-p24) between weeks _________
6 and 12
| may take 6 months or longer to achieve seroconversion
37
What is the latent asymptomatic period of HIV?
continuum of stage 1; asymoptomatic stage 2
38
How long does the latent asymptomatic period last?
Can last up to 8–10 years
39
What happens during the latent asymptomatic period?
* The virus disseminates throughout lymphoid tissue, incubates, replicates, and alters many physiologic processes, resulting in hyperimmune activation, persistent inflammation, and impaired gut function and flora
* Evolution of the virus within its host to generate closely related yet distinct mutant viruses that serve to evade the surveying immune response and circulating antibodies
* There is a **progressive decline in immune function evident as progressive depletion of CD4+ cell count** (CD4+ lymphocytes >500 cells/μL) & slow but usually progressive increase in viral load
40
____% of people with HIV are non-progressors and maintain a low viral load
<1%
41
What is the only symptom during the latent asymptomatic period?
persistent generalized lymphadenopathy (Up to 70% of patients
42
What are the features of HIV stage 2 (early symptomatic period)?
* Can last 1–3 years
* Signs and symptoms increase as the CD4+ count drops below 500 cells/μL and approaches 200 cells/μL (often between 200 and 300/μL)
* **Viral load continues to increase**
* Platelet count may decrease in about 10% of patients
43
Any combination of the following can occur during stage 2 HIV?
* Persistent generalized lymphadenopathy
* Fungalinfections
* Vaginal yeast and trichomonal infections
* Oralhairy leukoplakia (OHL)
* HerpesSimplex Viruses (HSV-1 & HSV-2)
* HerpesZoster (VZV)
* HIV-related retinopathy
* Constitutional symptoms: fever, night sweats, fatigue, diarrhea, weight loss, weakness
44
What are the features of stage 3 HIV (AIDS)?
* When the CD4+ count drops to below 200 cells/μL (also high viral load) or documentation of an AIDS-defining condition, the person has AIDS and is susceptible to opportunistic infections and maliganacies
* Platelet count may be low.
* Neutrophil count may be low.
* CD4+ cell count <50/μL at high risk for lymphoma and death
45
What are the opportunistic infections common in stage 3 HIV?
Pneumocystis jiroveci pneumonia, cryptococcosis, tuberculosis, toxoplasmosis, histoplasmosis, others
46
What malignancies are common with stage 3 HIV?
- Kaposi sarcoma
- Burkitt lymphoma
- non Hodgkin lymphoma
- primary CNS lymphoma
- invasive cervical cancer
- carcinoma of rectum
- slim (wasting) disease
47
Why does stage 3 HIV usually end in death?
because of wasting, opportunistic infection, or malignancies
48
What is a normal CD4/CD8 ratio?
1-4
49
CD4+ and CD8+ cell counts should be performed at the time of HIV diagnosis and then every _____________
3 to 4 months
50
Thereare three types of HIV tests available:
* Nucleic acid tests (NATs)
* Antigen/antibody tests
* Antibody tests
51
What are nucleic acid tests (NATs)?
* Detect the actual virus in the blood
* Polymerase chain reaction (PCR)–based assays of the viral RNA is performed to determine if a person has **HIV or the viral load** in the blood and monitor response to therapy
* **Detect HIV sooner** (superior) than other types of tests
* More expensive and not routinely used
* Detection ranges are from 40 copies/mL to more than 750,000 copies/mL. **The greatest viral load is found during the first 3 months after initial infection and during late stages** of the disease
52
What are antigen/antibody tests?
* Detect both HIV antibodies and antigens in blood samples
* In HIV-infected individuals, **p24** is produced even before antibodies develop
* Antigen/antibody tests are recommended for testing done in labs and are now common in the United States
* This lab test involves **drawing blood from a vein**. There is also a rapid antigen/antibody test available that is done with a **finger prick**
53
What are antibody tests?
* Only detect antibodies to HIV in **blood or oral fluid**
* In general, antibody tests that use blood from a vein can detect HIV sooner after infection than tests done with blood from a finger prick or with oral fluid
* **Most rapid tests** and the only currently approved HIV self test (OraQuick) are antibody tests
- Enzyme-linked immunosorbent assay (**ELISA**) testing for HIV in saliva is 98% sensitive in detecting antibodies to HIV
54
What is the OraQuick HIV test?
* Upper and lower gums are swabbed with the test stick
* Test stick is inserted into the kit's test tube which contains a developer solution
* 20-40 minutes wait time before reading the test result
* 92% sensitivity
* Additional testing should be done in a medical setting to confirm the test result:
--- Positive
--- Negative and exposure may have been within the previous three months
55
Current practice in medical setting is to screen first ________
ELISA
56
All positive results are then confirmed with ___________ analysis
Western blot
57
Positive ELISA and Western blot test results indicate only that the individual has...
been exposed to the HIV (do not indicate the status of the HIV infection or whether AIDS is present)
58
What are the features of antiretroviral medications (ARVs)?
- prescribed as an HIV drug regimen for the prevention and treatment of HIV/AIDS.
- Guidelines developed for effective drug therapy to treat HIV/AIDS in most patients living with HIV/AIDS incorporate a **three-drug regimen as a standard for long-term therapeutic effectiveness against the virus**
* ARVs selected as a part of an HIV regimen are** tailored to fit the patient’s specific needs** by taking into consideration the patient’s comorbidities or previous ART for example
59
The life expectancy of an HIV-infected individual appropriately treated with ART is now estimated to be...
nearly that of the general population
60
Current guidelines from around the world now recommend starting ART in all HIV infected patients, regardless of...
- CD4 cell count
- because of both clinical benefits to the patient and reduction in HIV transmission to others
61
Virologic suppression is defined as less than 48 copies/mL, and virologic failure is defined as a confirmed viral load of greater than ______ copies/mL in the presence of ART
200
62
Patients who are taking ART medications must be closely monitored for...
- drug effectiveness (which often wanes over time)
- development of antiviral resistance
- drug toxicity
- drug interactions
63
A way for people who do not have HIV but who are at very high risk of getting HIV to prevent HIV infection...
by taking a pill every day
- Pre-exposure prophylaxis
64
The pill (Truvada) contains two medicines ______________ that are used in combination with other medicines to treat HIV
(tenofovir and emtricitabine)
65
When someone is exposed to HIV through sex or injection drug use, tenofovir and
emtricitabine can work to keep the virus from...
establishing a permanent infection
66
All newborns who were exposed perinatally to HIV should receive...
postpartum ARVs to reduce the risk of perinatal transmission of HIV
67
Is there a vaccine for HIV?
not yet but studies are being done
