HIV & AIDS part 1 Flashcards
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.
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
—, while HIV-2 is more prevalent in — and associated with — disease course.
sub-Saharan Africa
Western Africa
slower
Since the onset of the worldwide pandemic, more than — people have
been infected with HIV, of whom approximately — have died because of
AIDS
70,000,000
35,000,000
An estimated — million people across the globe are newly infected with HIV
annually
2.7
By the end of 2019, approximately — million people were estimated to be living
with HIV
38
By the end of 2019, approximately 38 million people were estimated to be living
with HIV.
* Eastern and southern Africa ~—%
* Asia and the Pacific ~—%
* Western and central Africa ~—%
* Western and Central Europe and
North America ~–%
54
15
13
6
The vast majority of people infected with
HIV are in
low- and middle-income
countries.
Approximately — million people in the U.S. are living with HIV today
1.2
The Centers for Disease Control and Prevention (CDC) data indicate that the progress has stalled
in recent years, at about — new HIV infections each year between 2014 and 2018. HIV
incidence remained stable in 2018 at a rate of 13.3 (per 100,000 people)
38,000
By sex at birth, in 2018, the rate for males (22.1) was — times the rate for females (4.8)
5
By age group, in 2018, the number of new HIV diagnoses was highest among people aged —
25-44.
Initially in the United States, AIDS primarily affected
non-Hispanic whites and male
homosexuals.
- Today, — remains the
largest single risk factor with greater proportion
of cases arising in blacks/African Americans,
Hispanics/Latinos, females, and heterosexuals.
male-to-male sexual contact
- Although blacks/African Americans represented
only about 14% of the United States population,
they accounted for —% of new HIV infections.
(4) 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
44
Blood, semen, breast milk, and vaginal secretions
- Region of residence:
South
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
The most common method of sexual transmission in the United States is anal
intercourse in men who have sex with men (MSM), in whom the risk of HIV
infection is — times higher than in other men and in women
40
Heterosexual transmission (male to female or female to male) is the second most
common form of transmission in the United States but accounts for —% of the
world’s HIV infections
80
Transmission from — is the third largest group affected in the
United States
sharing needles
The risk of transmission from a blood transfusion is estimated to be — because of current screening measures.
less than 1 in
1 million
Children (< 13 yr) usually through — exposure (mother to infant). Casual
contact has not been demonstrated as a means of transmission.
perinatal
Transmission by — fluids is somewhat controversial and rarely documented.
oral
- — contains a number of HIV inhibitory factors, which appear to reduce the
ability of the virus to infect its target cells.
Saliva
- The presence of (3) may predispose an individual to oral transmission.
erosions, ulcerations, and hemorrhagic inflammatory pathoses
(e.g., gingivitis, periodontitis)
Gag
processed to matrix and other core proteins that determine retroviral core
Pol
reverse transcriptase, RNase H and integrase functions
Env
envelope protein, resides in lipid layer; determine viral tropism
Other antigens:
two regulatory proteins:
and four accessory proteins:
(Tat and Rev) that are essential for viral replication
(Nef, Vif, Vpu, Vpr).
Pathophysiology – Cell Cycle
(3)
Entry Replication Release
HIV primarily infects cells with — at the site of HIV entry
CD4 cell-surface
receptor molecules (CD4+ T helper lymphocytes
mainly)
Infection is aided by — cells in mucosal
epithelial surfaces which can become infected
delivering HIV to underlying T cells, ultimately
resulting in dissemination to lymphoid organs.
Langerhans
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)
The probability of infection depends on both the
number of — in the body fluid
which contacts the host and the number of cells
with — at the
site of contact
infective HIV virions
appropriate CD4 receptors available
Once within the cell, the viral particle uncoats from its spherical envelope to..
release its RNA
The enzyme product of the pol gene, a
— that is bound to
the HIV RNA, synthesizes linear
double-stranded cDNA that is the
template for —
reverse transcriptase
HIV integrase
It is this HIV proviral DNA which is
then inserted into the host cell
genomic DNA by the —
enzyme of the HIV
integrase
- Release of HIV from the host cell occurs in several steps.
- Just before the budding process,
— 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.
HIV protease
- 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.
(3)
- 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 —, the remaining >95% of quiescent lymphoid CD4 Tcells die by —
caspase-3-mediated apoptosis (~5%),
caspase-1-mediated pyroptosis triggered by abortive viral infection
- The spectrum of HIV disease changes as CD4+ cell count —.
declines
HIV particle is seen budding from the infected cell surface at the top, with a
complete viral particle at bottom in this high magnification electron micrograph.
— is the transition from the point of viral infection to when antibodies
of the virus become present in the blood (circulating antibodies).
Seroconversion
Stage 1 (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+ T lymphocyte percentage of total lymphocytes of
≥29***.
Stage 2 (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***.
Stage 3 (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 AIDSdefining condition. Documentation of an AIDS-defining condition supersedes a CD4+ T
lymphocyte count of ≥200 cells/μL and a CD4+ T lymphocyte percentage of total lymphocytes
of ≥14***.
Stage 1 (Immediately after HIV exposure)
During the first — weeks after initial infection with HIV, ~–% of patients develop an — syndrome marked by — (acute seroconversion syndrome) that may last – days
(sometimes up to 4 weeks). Others may not manifest this symptom complex.
2 to 6
70
acute flulike
viremia
10 to 14
Stage 1 (Immediately after HIV exposure)
Symptomatic persons often develop — -like symptoms: (11)
(roseola-like or urticarial). Only an estimated –% of symptomatic persons seek medical attention.
mononucleosis
lymphadenopathy, fever,
pharyngitis, weakness, diarrhea, nausea, vomiting, myalgia, headache, weight loss, and a skin rash
20
Stage 1 (Immediately after HIV exposure)
A concomitant transient — occurs along with high titers of plasma HIV, but patients
do not develop evidence of immunosuppression (>500 cell/ml; CD4+ cell count tend to return
toward normal levels after acute symptoms.
fall in CD4+ cells
Stage 1 (Immediately after HIV exposure)
This is usually followed by developing — between weeks —. A few may take – months or longer to achieve seroconversion particularly in patients
without acute symptoms. (6 weeks – 6 months, —% within the first – months of infection)
antibodies (anti-gag, anti-gp120, anti-p24)
6and 12
6
97, 3
Stage 1 (Immediately after HIV exposure)
The severity of the initial acute infection with HIV (i.e., level of viremia) is predictive of the course
the infection will follow. Generally, the — the acute infection lasts the — patients develop
AIDS.
longer
earlier
Latent asymptomatic period (continuum of stage 1; asymoptomatic stage 2)
* Can last up to ..
8–10 years.
Latent asymptomatic period (continuum of stage 1; asymoptomatic stage 2)
The virus disseminates throughout lymphoid tissue, incubates, replicates (several
thousand copies), and alters many physiologic processes, resulting in (3)
hyperimmune
activation, persistent inflammation, and impaired gut function and flora.
Latent asymptomatic period (continuum of stage 1; asymoptomatic stage 2)
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.
Latent asymptomatic period (continuum of stage 1; asymoptomatic stage 2)
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.
Latent asymptomatic period (continuum of stage 1; asymoptomatic stage 2)
* —% are non-progressors and maintain a low viral load.
<1
Latent asymptomatic period (continuum of stage 1; asymoptomatic stage 2)
Silent clinically except for persistent generalized
lymphadenopathy (Up to 70% of
patients).
Stage 2
Early symptomatic period
* Can last —
* Signs and symptoms increase as the —
* — continues to increase.
* — count may decrease in about 10% of patients.
1–3 years.
CD4+ count drops below 500 cells/μL and
approaches 200 cells/μL (often between 200 and 300/μL)
Viral load
Platelet
Any or a combination of the following:
- Persistent generalized lymphadenopathy
- Fungal infections
- Vaginal yeast and trichomonal infections
- Oral hairy leukoplakia (OHL)
- Herpes Simplex Viruses (HSV-1 & HSV-2)
- Herpes Zoster (VZV)
- HIV-related retinopathy
- Constitutional symptoms: fever, night sweats, fatigue, diarrhea, weight loss,
weakness.
Stage 3 (AIDS)
When the CD4+ count drops to below — 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.
200
Stage 3 (AIDS)
Opportunistic infection(s):
Pneumocystis jiroveci
pneumonia, cryptococcosis, tuberculosis, toxoplasmosis,
histoplasmosis, others
Stage 3 (AIDS)
* — count may be low.
* — count may be low.
* CD4+ cell count —/μL at high risk for lymphoma and
death.
Platelet
Neutrophil
<50
skipped
Stage 3 (AIDS)
Malignancies:
Kaposi sarcoma, Burkitt lymphoma, nonHodgkin lymphoma, primary CNS lymphoma, invasive
cervical cancer, carcinoma of rectum, slim (wasting)
disease
Stage 3 (AIDS)
Death usually occurs because of (3)
wasting, opportunistic
infection, or malignancies.
- The CD4/CD8 ratio reflects —-. A normal ratio is between
immune system health
1 & 4.
CD4+ and CD8+ cell counts should be performed at the time of HIV diagnosis and
then every
3 to 4 months.
There are three types of HIV tests available:
- Nucleic acid tests (NATs)
- Antigen/antibody tests
- Antibody tests
HIV tests are typically performed on
blood or oral
fluid. They may also be performed on urine.
Nucleic acid tests
- 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 (i.e., degree of viremia)
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.
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. - E.g., Abbott has developed a combination assay, the ARCHITECT HIV Ag/Ab
Combo assay (Abbott Laboratories, Abbott Park, IL), that can simultaneously detect
the combined presence of HIV antigens (p24 antigen) and antibodies to HIV. This test
is important for diagnosing HIV infection in the acute phase of the disease when
antibodies are not yet present and for ongoing monitoring of patients.
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 selftest (OraQuick) are antibody tests.
- Enzyme-linked immunosorbent assay (ELISA) testing for
HIV in saliva is 98% sensitive in detecting antibodies to
HIV.
OraQuick
- Upper and lower gums are swabbed with the test stick.
- Test stick is inserted into the kit’s test tube (vial) 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
Current practice in medical setting is to screen —. If the results are
positive, a — is performed (due to high rate of false positive). All
positive results are then confirmed with — analysis. This combination
of tests is accurate more than 99% of the time and the patients are considered
potentially —.
first ELISA
second ELISA
Western blot
infectious
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).
National surveys conducted on American general dentists predicted their
willingness in implementing —during dental visits.
oral HIV rapid testing
Although opposed by challenges of cost, licensing, and patient acceptance,
potential models for integrating — screening into routine dental practice have
been proposed representing a step forward towards early detection of the
disease.
HIV
Highly active antiretroviral therapy, now known as combined antiretroviral therapy
(cART) or ART, refers to the
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
The life expectancy of an HIV-infected individual appropriately treated with ART is now
estimated to be nearly that of the general population, both in developed and developing
countries, although it also is estimated to be about — than in healthy people
with no comorbid conditions.
1.7-fold higher
Current guidelines from around the world now recommend starting ART in all —- because of both clinical benefits to the
patient and reduction in HIV transmission to others.
HIVinfected patients, regardless of CD4 cell count
skipped
Examples of FDA-approved HIV Regimens
- Lamivudine & tenofovir disoproxil fumarate (Cimduo)
- Emtricitabine & tenofovir alafenamide (Descovy)
- Emtricitabine & tenofovir disoproxil fumarate (Truvada)
- Bictegravir, emtricitabine, & tenofovir alafenamide (Biktarvy)
- Emtricitabine, rilpivirine, & tenofovir disoproxil fumarate (Complera)
- Emtricitabine, rilpivirine, & tenofovir alafenamide (Odefsey)
- Elvitegravir, cobicistat, emtricitabine, & tenofovir alafenamide (Genvoya)
- Elvitegravir, cobicistat, emtricitabine, & tenofovir disoproxil fumarate (Stribild)
Patients who respond to therapy generally show an increase in CD4+ count in the range of — cells/μL per year and viral loads of less than – copies/mL.
50 to 150
5
Virologic suppression is defined as less than – copies/mL, and virologic failure is defined as a
confirmed viral load of greater than — copies/mL in the presence of ART.
48
200
Patients who are taking ART medications must be closely monitored for drug effectiveness
(which often wanes over time), development of antiviral resistance, drug toxicity, and/or drug
interactions
* — is recommended when treatment is failing.
Antiviral resistance testing
skipped
* Some important toxicities include (5)
hyperlactemia, mitochondrial dysfunction, peripheral
neuropathy, hepatotoxicity, and lipodystrophy.
Pre-exposure prophylaxis
* 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.
The pill (brand name Truvada) contains — medicines (tenofovir and
emtricitabine) that are used in combination with other medicines to treat HIV
two
When someone is exposed to HIV through sex or injection drug use, these
medicines can work to keep the virus from
establishing a permanent infection
Management of Infants Born to Women with
HIV Infection
* All newborns who were exposed perinatally to HIV should receive
postpartum
ARVs to reduce the risk of perinatal transmission of HIV.
