Module 5-2 - HIV Flashcards
How big is the HIV issue?
1 in 7 do not know they have it and over 1 million in the US have it alone
Globally 37.9 million have it and 32 million have died
In what groups has the highest Incidence of HIV?
African American gay and bisexual men, but Latino gay and bisexual men have increased in incidence over time
What area of the US has the largest incidence of HIV?
The South (52%)
What does HIV stand for?
Human Immunodeficiency Virus
What does AIDS Stand for?
Acquired Immunodeficiency Syndrome
It is the late stage of HIV and is the disease caused by it
What is the structure of an HIV viral particle?
Oval Shaped Protein Coat
Capside with RNA, enzymes, P24 Protein, and P17
Envelope with the lipid layer, GP120 and GP41 - Glycoproteins sticking out of the lipid membrane
What is special about the HIV P24 protein?
This protein serves as an antigen that we can test for antibodies and for the the virus presence/antigen
GP120 and GP 41
Glycoproteins that are like spikes sticking out of the lipid membrane and aids HIV in getting into cells
What is one of the components of HIV that makes it unique?
It contains reverse transcriptase enzyme
Most viruses cannot…
replicate on their own, they need to be in a cell to reproduce
Retrovirus
HIV
it inserts itself as vRNA and makes DNA from the vRNA, and then splices the vDNA into the genetic material of healthy cells
So, it enters the hosts genetic material causing a permanently infected cell
What does a new virus take from an infected cell when leaving?
It takes the phospholipid bilayer for itself
Capsid
The protein shell of a virus containing its genetic material
It has 2 strands of RNA, Reverse Transcriptase, and P17 and P24 proteins in it (in HIV)
Envelope
Lipid bilayer containing the virus and capsid that has GP120 and GP41 sticking out of it (in HIV) allowing access to cells
Made from the host cells membrane as it left the cell
How exactly does a retrovirus infect cells?
The GP120 and 41 on the surface allow it to bind to CD4 receptors on T4 cells and then inject its contents into the cytoplasm
The contents (2 RNA strands and reverse transcriptase) can then be used to make DNA
What aspect of HIV causes the immune deficiency disorder?
The fact that it infects and hurts T4 cells (thus hindering the immune response)
What occurs once reverse transcriptase uses the viral RNA to make DNA?
The DNA then goes from the cytoplasm into the nucleus, and along with other viral enzymes, inserts itself into the host cell genome
Once vDNA is inserted, its there permanently and the cell is infected and no longer your own
RNA can then be made using the DNA to make virions using the cells machinery
What can occur after the vDNA has entered the genome?
It can either go latent or activate and begin making viral particles (RNA and RTranscriptase)
Latent
A virus that inserts itself and remains dormant, not producing new viral particles
It can do this if there is not the right kind of GP on the surface or if the formation of a capsid hasn’t progressed to maturity yet for example
What happens once vDNA activates to make new Virions?
Proteases will cleave proteins made by viral mRNA and package them into a protein coat
The viral particles can then be put into the protein coat to make the immature capsid
The capsid can eventually make an envelope using the phospholipid bilayer of the cell and bud off the membrane to go make more infected cells and copies
Thera re classes of HIV meds addressing…
every step of HIV reproduction
What happens since the new virion takes a chunk of the membrane with it?
It will have GP120 and GP41 on its surface of the envelope
Can then connect to CD4 on other T4 cells and invade as a result
Where do the names of GP120 and GP41 come from?
their molecular weight
Why can T8 cells have difficulty killing virus infected cells?
If the virus DNA is already in the nucleus, the T8 cell cannot identify that the cell is infected unless the virus is actively replicating already
HAART
Highly Active Antiretroviral Treatment
HIV treatment method
It involves hitting the disease fast and hard as soon as you learn of infection with drugs that will eradicate it ASAP - its trying to prevent viral particles from seeding and allowing reproduction later
Seeding
When the viral DNA goes dormant and remains undetected and safe until it can widely disseminate and activate
Because of seeding, it is important to destroy all viral particles before seeding occurs to allow greater survival probability
Wanna stop this fast and early
Summation: Stages of Viral Replication
- HIV binds to the CD4 cell on T4 cells and RNA, proteins, and enzymes released into cytoplasm
- HIV Reverse Transcriptase converts vRNA into vDNA
- HIV vDNA then moves to the host nucleus and is spliced into the host genome/DNA
- HIV vRNA moves out of the nucleus to the cytoplasm and makes long chains of viral proteins and enzymes
- Immature viral particle forms containing cellular and HIV protein. Chains cut into smaller pieces by protease
- Infectious viral particle is now ready to be released containing HIV RNA, viral proteins and enzymes
The function of the immune system?
Function = Prevent/Fight Disease
It controls of eliminates viruses and other microbes that threaten the body with infection and disease
It eliminates damaged cells that are or may be cancerous
The immune system is divided into two branches…
- Antibody Mediated –> Copes with disease causing microbes in the blood
- Cell Mediated –> Copes with microbes located within cells
When does Cell Mediated Response v Humoral Response get to the viral particles compared to each other?
Humoral response get to the virus before it even enters the cell and cell mediated gets there after
What is so important about CD4 cells and HIV?
CD4 cells (Helper T Cells) coordinate and activate both B lymphocytes (antibody mediated) and cell killing cytotoxic (CD8) lymphocytes (cell mediated) - the cell mediated response copes with microbes located inside cells like viruses
However, HIV can infect and destroy CD4 cells (gets your body to attack the Helper cells since they are infected) –> loss of CD4 means the immune system will collapse with HIV disease
What is used as a marker of the progression of HIV?
Decline in (Absolute) CD4 cells
When are CD8 cells important for HIV infection?
In the initial immune response to HIV and the latent stage
What do CD8 cells do?
They kill infected cells that are producing virus
What can CD8 cells do to prevent HIV replication?
- They can kill the cell
- They can secrete soluble factors that suppress HIV replication by blocking and occupying receptors needed for the entry of certain strains of HIV into the target cell
What are the two issues that exist with HIV and CD8 cells ?
- If the CD8 cannot get the job done early enough, the HIV virus can seed, and once latent the CD8 cells cannot detect them until its too late
- New info shows 2 new strains of the HIV virus that target CD8 cells as well as CD4
If CD4 cells are infected with HIV, what occurs with CD4 cells to lead to increased susceptibility to opportunistic and other infections?
CD4 can not make interleukins to stimulate an immune response –> loss of stimulus for T and B cell activation occurs –> lymphopenia, decreased CD4/Cd8 ratio, and decreased delayed hypersensitivity –> increased risk
If CD4 cells are infected with HIV, what occurs with CD8 cells to lead to increased susceptibility to opportunistic and other infections?
CD8 cells have impaired feedback and cytotoxic activity since they cannot get orders from CD4 –> lymphopenia, decreased CD4/Cd8 ratio, and decreased delayed hypersensitivity –> increased risk
If CD4 cells are infected with HIV, what occurs with Macrophage cells to lead to increased susceptibility to opportunistic and other infections?
Macrophages have decreased chemotaxis, phagocytosis, IL-1 production, and ability to present antigens to cells (d/t no T4 response) –> Increased risk
If CD4 cells are infected with HIV, what occurs with B cells to lead to increased susceptibility to opportunistic and other infections?
B cells have diminished antibody production in response to antigens and decreased production of immunoglobulins –> decreased nonspecific serum immunoglobulin –> increased risk
Why does a drop in ratio between CD4 and CD8 cells cause delayed hypersensitivity?
It is referring to Type IV hypersens. (no antibodies)
There is no T4 stimulation leading to not enough T8 cells reacting to something to have an immune response happen
Absence of an immune response may mean…
either you do not have an infection or you could have no immune system
Anergy
No immune system and cannot mount an immune response
Why may we want to give an HIV patient a Tb test?
It is a common comorbidity
If we give the test and wait for the response and there is none, then they may not have enough T8 cells rather than not have Tb
What is a way to check if you have no immune system (anergy) or no exposure?
Expose them to yeast / yeast mold antigen which almost everyone has been exposed to
If they react to the yeast injection, they have no been exposed to Tb and have an immune system, but if they are Anergic they will not react to the yeast either
Which Interleukin is important for Chemotaxis?
IL-1
Why does macrophage presenting ability decrease with HIV?
T4 cells are not producing the needed cytokines that are supposed to amplify and stimulate and immune response
Those with HIV end up with strange rates of…
cancer and infection
What is HIV replication rate like?
Crazy fast early on - billions per day with a high mutation rate (3300 mutants made per day)
99% of HIV in the blood is from newly infected cells
30% of HIV in plasma is replenished daily
How many days does it take for HIV entire population turnover?
14 days
What is the mutation rate of HIV?
1 in 3 replication cycles - 3300 mutant viruses per day
When does extensive HIV seeding occur?
early in the disease process
CD4 only has a lifespan of 1-2 days so if HIV is not taken care of early then the extensive seeing will occur
Sanctuary Sites
Body has a difficult time detecting HIV in these areas
HIV gets to these areas by going inside macrophages and crossing into the CNS to cause dementia (like a macrophage trojan horse)
These are the dendritic cells of the lymph nodes and glial cells of the CNS
Lifespan of a CD4 Cell
1.2 days (billions made, infected, and destroyed daily in HIV)
What happens to T4 cell levels over time with HIV?
The T4 infected cells will eventually be attacked by CD8 cells killing them and infected macrophages
Eventually you run out of T4 cells to keep up with viral replication rate
Transmissible Body Fluids for HIV
Blood
Semen
Vaginal Secretions
Breast Milk (so this is contraindicated in HIV+ women)
Cerebral Spinal Fluid
Synovial Fluid
Pleural and Amniotic Fluid
Non Transmissible Body Fluids for HIV
Urine
Sweat
Saliva
Tears
Vomit
Mucus
Feces
The virus can be found here but not transmitted here
How can vertical transmission of HIV be very low?
IF the mother is compliant with medication regimen
2-8% rather than 15% without (or 29% to 2% with AZT treatment)
Methods of Transmission for HIV
- Unprotected sex - oral, anal, vaginal
- Blood to blood contact - sharing needles, occupational exposure, fighting, tattooing, body piercing, transfusions
- Mother to newborn - in utero, childbirth, breast feeding
Risk Factors for HIV Infection
Sexual Activity
Injection Drug Use
Recipients of Blood Products (1975- March 1985)
Hemophiliacs who received Pooled Plasma
Children of HIV Infected Women
Needlestick accidents
How many children of HIV infected women will be infected without treatment?
30%
What is used to immediately treat post exposure needlestick accidents?
Retrovir (Zidovudine) - given ASAP within 24 hours!
What is the greatest HIV transmission risk?
Receptive Anal Intercourse (receptive meaning semen stays inside, and the membranes tear in this case)
there is a 95% chance of getting it from HIV infected blood donors but this rarely occurs nowadays
What is the least HIV transmission risk?
Insertive Vaginal intercourse is 1/10,000 chance (insertive meaning penis goes in but ejaculate was not)
There is a 1/1,000,000 chance to get HIV from screened blood though
Other Factors that increase HIV Risk?
- Acute infection about 12 weeks after HIV contraction makes transmission likelihood 26x more likely
- Other STIs can amplify risk x8
- Exposure to gender inequality and intimate partner violence can raise a womans HIV risk x1.5
Why is it that your HIV transmission risk is 26x more 12 weeks after contraction (during acute infection)?
the viral load has skyrocketed during the acute phase is why
Other factors that decrease HIV risk?
Circumcision (60%) lower in hetero males
Treatment as prevention
Pre exposure prophylaxis
Condoms (80% lower)
Only having intercourse with someone of the same sero status (HIV-HIV, Negative-Negative)
Tests for HIV
ELISA
Western Blot
p24 Antigen
Absolute CD4+ Lymphocyte count and CD4 Lymphocyte Percentage
HIV Viral Load Tests
CBC
DNA - Viral nucleic acid tests
Viral Culture
Immunofluorescence Antibody Testing
Urine and Saliva Serologic Testing
Home Testing
ELISA Testing
Enzyme Linked Immunosorbent Assay
Determines response of antibodies to HIV Virus
Used in children older than 18 mo
High sensitivity with low specificity - so lots of false positives
There is a plate of viral particles mixed and if there is antibodies they will bind to the antigens on the bottom of the plate, then if more antibodies that change color are added then it is a positive case
If blood washes off and no color change occurs it is negative
What is ELISA good as?
A Screening Test
High sensitivity means it can rule out those without HIV but low specificity means you can have a lot of false positives
Western Blot Testing
Confirms the presence of HIV Antibodies and is more specific for HIV
Useful children 18 mo and up
Positive HIV antibody test in children younger than 18 mo only indicates the mother is infected
What are the most common HIV tests?
ELISA and Western Blot
How are ELISA and Western Blot used together
You can be confident in a negative ELISA test, but if there is uncertainty with a positive you can confirm it with a western blot (which sorts out the false positives)
P24 Antigen Test
Used to detect HIV Antigen in children <18 mo
Test can be useful at any age
Only a positive result is significant!
2 or more positive results are diagnostic for HIV Infection
It looks for the p24 protein on HIV - so this test looks for the actual virus rather than antibodies like in ELISA and W Blot
Why may a p24 Antigen Test be used immediately upon suspicion?
Since ELISA and W Blot take 3-6 months since thats how long it takes to make antibodies, this can be positive for looking the virus itself while the the other two can come out false negative if done too early
In what situation is a p24 Antigen test very helpful?
For immediate use after finding out your partner is HIV+
CD4+ Testing
Used to assess immune status, risk for disease progression and need for PCP Prophylaxis
This checks for the CD4+ (T4/Helper Cells) and can be used to see how the immune system is working and how far an already known case has progressed
DNA HIV - Viral Nucleic Acid Tests
ex: PCR - Polymerase Chain Reaction, Nucleic acid sequence based amplification, Branched chain DNA tests
These kinds of tests look for minute amounts of HIV and use special replication processes to make things larger and large until we can get a viral load that is detectable and countable
What is a massive advantage to DNA HIV - Viral Nucleic Acid Tests?
They can shorten the window period allowing detection of HIV in as little as 12 days
HIV Viral Culture
Highly specific test
Negative results are meaningless since it can be very difficult to grow
Not frequently used to diagnose HIV
IAT (Immunofluorescence Antibody Testing)
Alternative to the western blot in order to confirm HIV infection
A positive ELISA can be followed by a W Blot or IAT
Urine and Saliva Serologic Testing (EIA)
Ex: Urine EIA, Saliva EIA, Rapid Enzyme EIA
This tests for HIV Antibodies
Home Testing
Fingerstick specimen is sent to a laboratory to detect HIV
Significance of an ELISA HIV Test
It is a screening test for HIV Antibodies
Significance of Western Blot and IAT for HIV?
Confirmatory Tests for HIV Antibodies
CBC for HIV Significance
Anemia, Neutropenia, and Thrombocytopenia indicate infection
Shows blood manifestations that may occur as a result of the disease
Absolute CD4 Lymphocyte Count Significane
Predictor for HIV Progression and immune function
What level of CD4 indicates an increased risk for infection and malignancy (count and percentage)?
CD4 <200 cells/mcL
CD4 <20%
CD4 Lymphocyte Percentage Significane
Predictor for HIV Progression and monitors immune function
HIV Viral Load Test Significance
Measures the amount of actively replicating HIV and correlates levels with disease progression
Can also monitor disease activity
P24 Antigen Test Significance
Indicates active HIV replication is occurring
Cannot give a definite negative, but a positive can be detected through finding HIV viral particles quickly
What are the Laboratory Criteria for a positive case of HIV?
- Positive result from an HIV antibody screening test, i.e. ELISA, confirmed by a positive result from a supplemental HIV antibody test, i.e. W blot.
OR
- Positive result or report of a detectable quantity from any of the following HIV virologic (NON ANTIBODY) Tests: HIV Nucleic Acid Detection Test (i.e. PCR), HIV pp24 Antigen Test with Neutralization Assay, or HIV Isolation (Viral Culture)
What is the overall takeaway about HIV Diagnosis?
Results are rarely determined by just one test, need multiple
HIV Disease Process Definition
A chronic infection (no longer a death sentence) with a very variable course (may take a while, but extensive seeding worsens prognosis)
It infects cells with CD4 receptors (T4 / Helper T Lymphocytes)
Leads to cell death and decline in immune function
S/S of HIV (Pre Symptomatic Phase)
Acute Infection
Self Limited Syndrome lasting 6-8 weeks post infection
Associations with development of HIV Antibody
Asymptomatic Infection/Period
Persistent Generalized Lymphadenopathy
Acute HIV Infection
Initial symptoms in the window period / up to 6-8 weeks post infection associated with antibody development
Not often equated to HIV
S/S: - Flu Like: Mononucleosis Like Syndrome Fever Rash Myalgia Malaise
Asymptomatic HIV Infection
Period following initial infection
Variable duration (depends on treatment)
No S/S except potential persistent generalized lymphadenopathy
During this time ELISA can show you have antibodies indicating exposure
Persistent Generalized Lymphadenopathy (PGL)
Lymph node enlargement 1 cm or greater in two or more extra-inguinal sites (generalized in the body and they are persistent and stay large in the neck, arm, etc)
It is assoc with inflammation and infection in the nodes
Adenopathy is if they are 1 cm in 2 or more extra inguinal sites for longer than 3 months!
HIV Disease Spectrum
- 1-3 mo: HIV infection / Window Period- Flu like symptoms
- 1-10+ Years: Asymptomatic Period - no symptoms, except potential PGL
- Post-Asymp.: Symptomatic Period - after the immune system is worn down
- Post Symptomatic and Meets Criteria: AIDS
Window Period
Time 1-3 months post infection when antibodies are formed and the initial HIV infection occurred
It is a window since we generally cannot diagnose the disease during this time
What are some S/S that begin to occur once the immune system is worn down by HIV and the symptomatic period begins?
Fatigue
Diarrhea
Fever
Thrush
Skin Rash
Weight Loss
Swollen Glands
Thrush
Yeast infection in the mouth
Commonly seen in symptomatic HIV Patients
Is infection and symptoms occurring indicative of HIV becoming AIDS?
NO
Infections will occur more without an immune system, but there are defining conditions for AIDS
These infections are opportunistic and could occur to anyone, but AIDS defined conditions are highly unusual
AIDS Stage
Final stage of HIV Infection
The conditions defining AIDS are significant opportunistic conditions such as oral candidiasis in the mouth down to the throat and esophagus
Who determined what conditions are defining conditions of AIDS?
WHO
Course and general time periods for the Clinical Presentation of HIV Infection
- Window Period/Acute Infection - no antibodies, flu like symptoms - within 2-4 months post infection
- Asymptomatic/Subclinical Phase - virus and antibodies are present with no symptoms except lymph enlargement, and can be tested for during this period - 4 months to about 8+ years
- HIV Related Disease/Symptomatic Period - Infections begin to occur as the immune system weakens, but not the massive once indicative of AIDS - Whenever subclinical phase ends until onset of AIDS
- AIDS - about 10 years out if they follow treatment - severe opportunistic conditions that can cause death
How does Viral Load for HIV change over the course of infection?
Initially there is a large spike from reverse transcriptase and new replication, but they are killed off quickly
But once the immune system cannot keep up, the seeded HIV will rise again and win over the body
How do HIV Antibody levels change over the course of infection?
Initially upon infection there will be none with some initial IgM followed by IgG response typical of immune response
Overtime IgG will rise over several months and then plateau
As HIV destroys T4 cells, B cells will not activate and this means there is less IgG, so overtime the levels will drop
At the end of life they are anergic with no antibodies left - so there wouldn’t even be a Tb reaction upon testing!
How does CD4 Cell Count change over the course of HIV infection?
T4 will initially go up during the first few months and drop during the acute infection, but during the asymptomatic period it will gradually decline (while viral load increases)
Once low enough major opportunistic infections occur resulting in AIDS
What level of CD4 is indicative of major opportunistic infections and an AIDS diagnosis?
Below 200 cells/mcL
Below 600 indicates the non normal range
Infection Staging of HIV
Stage 1
Stage 2
Stage 3 (AIDS)
HIV Infection, Stage Unknown
Stage 1 HIV
No AIDS Defining condition AND EITHER:
- CD4+ T Lymphocyte count of >500 cells/mcL
OR - CD4+ T Lymphocyte percentage of total lymphocytes of > 29%
*No s/s occur during this time
Stage 2 HIV
No AIDS Defining Conditions AND EITHER
- CD4+ T Lymphocyte count of 200-499 cells/mcL
OR - CD4+ T Lymphocyte percentage of total lymphocytes of 14-28%
Stage 3 HIV
Full Blown AIDS:
CD4+ T Lymphocyte of <200 cells/mcL
OR
CD4+ T Lymphocyte percentage of <14%
OR
Documentation of AIDS defining condition
What supersedes CD4+ count and percentage for an AIDS diagnosis?
An AIDS defining condition
If you have an AIDS condition, you have AIDS, regardless of the count
HIV Infection, Stage Unknown
No information available on CD4+ T Lymphocyte count or percentage, and no information available on AIDS defining conditions
What is a major cause of death and comorbidity during Stage 3 HIV?
Tuberculosis (Tb)
HIV has __ Effects
Systemic
*It spreads through the whole body and effects all systems and organs of the body - just having systemic symptoms may not cause you to think of HIV immediately though until you get an AIDS defining condition
Areas of the Body that may have HIV Systemic Effects occurring?
Systemic
Sinopulmonary
CNS Diseases
Peripheral Nervous System Disease\
Rheumatologic Manifestations
Myopathy
Oral Lesions
Retinitis
GI Manifestations
Endocrine Manifestations
Skin Manifestations
Inflammatory Reactions
HIV Related Malignancies
Gynecologic Manifestations
IT IMPACTS EVERYTHING!!!!!
What are some examples of the systemic effects of HIV?
Fever
Night Sweats
Weight Loss
Nausea
(These things compounded with other system effects can lead to poor body image and also increased incidence of cancer)
Informational Card:
What are some Sinopulmonary systemic effects of HIV?
Pneumocystis Carinii PNeumonia (AIDS defining)
Non infectious Pneumonia
Sinusitis
Informational Card:
What are some CNS Disease systemic effects of HIV?
toxoplasmosis
CNS lymphoma
AIDS DEMENTIA!!! Complex
Cryptococcal meningitis
HIV Myelopathy
Progressive multifocal leukoencephalopathy
Informational Card:
What are some PNS disease systemic effects of HIV?
Peripheral Neuropathy
Informational Card:
What are some rheumatologic manifestation systemic effects of HIV?
arthritis
SLE
Informational Card:
What are some myopathy systemic effects of HIV?
Proximal muscle weakness
Informational Card:
What are some oral systemic effects of HIV?
oral candidiasis
hairy leukoplakia
angular cheilitis
gingivitis
aphthous ulcers
Informational Card:
What are some retinitis systemic effects of HIV?
CMV (cytomegalovirus)
blindness
Informational Card:
What are some GI manifestation systemic effects of HIV?
Candidial esophagitis Hepatic disease Biliary disease Enterocolitis Gastropathy Malabsorption syndrome
Informational Card:
What are some endocrine manifestation systemic effects of HIV?
Adrenal insufficiency
Thyroid function
Informational Card:
What are some skin manifestation systemic effects of HIV?
Herpes simplex infections Herpes zoster Molluscum contagiosum Folliculitis Superficial abscesses Bullous impetigo Bacillary angiomatosis Fungal rashes Kaposi’s sarcoma Seborrheic dermatitis Xerosis Psoriasis
Informational Card:
What are some inflammatory systemic effects of HIV?
Unusual presentations of opportunistic infections
Informational Card:
What are some HIV related malignancy systemic effects of HIV?
Kaposi’s sarcoma Non-Hodgkin's lymphoma Hodgkin’s Disease Anal dysplasia & squamous cell carcinoma Cervical dysplasia & neoplasia
Informational Card:
What are some gynecologic manifestation systemic effects of HIV?
Vaginal candidiasis
Cervical dysplasia & neoplasia
Pelvic inflammatory disease
What are the treatment guidelines like for HIV?
Treatment guidelines have changed many times
Many views on this subject –> ultimately decision to begin treatment rests with the patient and the doctor
There are HIV treatment guideline portals for use as well
Drug Resistance Testing
Testing recommended when entering care (regardless of therapy or treatment and whether it begins immediately) to check for HIV resistance to drugs
Should be used to determine what drugs should be selected when changing antiretroviral regimens
Types of Drug Resistance Testing for HIV
Genotypic Assays
Phenotypic Assays
Genotypic Assays
Detects drug resistance mutations present in relevant viral genes
this one is generally preferred for antiretroviral (drug) naive persons
usually done first to identify the strain, and then if treatment fails a phenotypic assay is done
Phenotypic Assay
Like a sensitivity test
measures the ability of a virus to grow in different concentrations of antiretroviral drugs
Is Genotypic Resistance Testing recommended for pregnant women?
Yes
It should be done prior to initiation of therapy and for those entering pregnancy with detectable HIV RNA levels while on therapy
What are the HIV Treatment Goals
- Reduce HIV Related Morbidity and prolong survival (it is no longer death sentence, its a chronic condition)
- Improve quality of life
- Restore and preserve immunologic function (keep T4 high)
- Maximally and durably suppress viral load (use antiretroviral drugs)
- Prevent vertical HIV transmission
HAART
Highly Active Antiretroviral Treatment
It is a treatment to keep the HIV viral load to undetectable levels and minimize seeding of the lymphatic system with HIV by hitting it fast, hard, and early
Its a multi drug approach though to strike at various points of the viral life cycle
What things do the multiple drugs in HAART do?
- Decrease development of resistance to medications
2. Minimize medication toxicities (by having many drugs at low doses)
What can make HIV treatment difficult?
If there is extensive seeding and the virus is latent
The drugs that treat cancer and HIV vary enough so that they …
can prevent steps at all phases of viral/cancer replication
What can be difficult about HAART?
While we give low doses of multiple drugs to decrease toxicity and SE, the side effects are sometimes too much for people and they stop taking them (which can lead to viral resistance)
The older treatment drugs used to be far hasher as well on people
What is a common drug used in HAART?
AZT
What has HAART done for the HIV epidemic?
It has boosted treatment as prevention and greatly reduced progression to AIDS
This keeps T4 higher and keeps the viral load down to stay asymptomatic longer
What viral load amount of HIV makes transmission almost nil?
50 copies per mililiters
What categories of pharmacotherapeutics are important for treating HIV
- Antiretrovirals
2. Treatment Regimens
What are the major categories of Antiretrovirals
- Nucleoside Revers Transcriptase Inhibitors
- Non-nucleoside Reverse Transcriptase Inhibitors
- Protease Inhibitors
- Fusion Inhibitors
What are important considerations for treatment regimens for HIV?
- Combination therapy with demonstrated clinical benefit (helps reduce toxicity)
- Do Treatment with agents no previously exposed to
- Non-overlapping toxicities & avoid negative synergism (drugs inhibit each other’s activity - avoid these)
Reverse Transcriptase Inhibitors
Antiretroviral
Acts early in the HIV life cycle
Prevents the HIV enzyme from making vDNA from vRNA –> prevents new viruses from being produced since it cannot make DNA to get into the genome
2 forms: nucleoside and nonnucleoside
Breaks the “teeth off the DNA zipper”
What is the difference between Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitors?
Nucleoside - work by chain termination and competitive inhibition of nucleoside triphosphates - this affects the building blocks of vDNA
Nonnucleoside - Do NOT need intracellular phosphorylation for activation; Directly bind to and disrupt catalytic sites of revers transcriptase –> chain termination — so this one works on the enzyme to cause chain termination at the catalytic site
You can salvage an attacked cell if..
you get to it before vDNA is produced
Protease Inhibitors
Antiretrovirals
Act late in the life cycle of the HIV
Block HIV enzyme proteases –> prevents creation or cleavage of HIV polyproteins needed for production of new virions
It prevents proteins produced from ribosomes from making the capsid, thus preventing virion babies
Fusion Inhibitors
Antiretrovirals
Act very early in the cycle by preventing viral contents from even getting in!
Attach to proteins on the surface of T cells or HIV
Prevent the binding of proteins on HIVs outer coat (GP120 and GP41) with surface receptors of T cells (CCR5 and CXCR4 = CD4 receptors)
Newest kind of med but one of the best to prevent seeding
Enfuvirtide
Fusion inhibitor that binds to GP41 to prevent HIV from binding to cells
Pre-Exposure Prophylaxis (PrEP)
Prevention medication - ex: truvada
Given to HIV(-) people who engage in risky behaviors in order to prevent HIV infection
Blocks HIV Reverse Transcriptase
MUST BE TAKEN DAILY TO PREVENT
Requires quaterly testing for HIV, STDs, and SEs
Who else can take PrEP?
No just negative HIV prevention cases, but also positive individuals can take it as a reverse transcriptase inhibitor
Side Effects of PrEP
Nausea
Mild Bone Density Loss
Kidney Problems
(all stop once meds are done)
Downfall of PrEP prevention
- no protection against other STDs
- needs to be taken daily
- needs quarterly testing for HIV, STDs, and SE
Common HIV Drug Side Effects
Diarrhea
Pancytopenia
Dyslipidemias
Lipodystrophy
Lactic Acidemia
Hypertriglyceridemia
Nephrolithiasis
Insulin Resistance
What is the key issue for HIV drug treatment?
ADHERENCE
They must adhere to get maximal and durable suppression of HIV activity and immune preservation or prevent the infection
It can be tough because of the SE (like potential type II diabetes)
Why is Adherence to HIV drugs such a big issue?
- Optimum therapeutic response needs adherence
- Treatment failure leads to increased seeding in lymphoid reservoirs
- Adherence is the only thing preventing drug resistance
Lipodystrophy
fat redistribution
The fat goes to become central fat or a buffalo hump - but this is moreso the case in older meds we rarely use now
What is the prognosis for untreated HIV–>AIDS?
life expectancy of 2-3 years
When does AIDS usually develop?
When CD4 < 200
What is CD4 decline like in untreated HIV?
declines at about 50-80 per year and gets more rapid as it drops below 200
What is the important takeaway about treatment of HIV presently?
Potent antiretroviral regimens may delay or even reverse immune dysfunction - now people can live long and relatively healthy lives
Who is the major group of Pediatric HIV patients?
Newborns that contracted it from their mother either through placenta, blood exchange during vaginal delivery, or milk during breastfeeding
When do pediatric HIV symptoms usually develop?
Within 6 months
What is the life expectancy of a pediatric HIV patient?
<3 years old
What is the transplacental infection rate for giving HIV to a newborn?
30% (chance to give via placenta)
Treatment of an HIV+ mother can reduce perinatal transmission by how much?
66%!
This brings vertical transmission chance from 30% down to 2%
Post Exposure Prophylaxis
Universal precautions and prophylaxis used in order to treat accidental exposure to HIV for a healthcare worker like a needlestick accident
Post Exposure Prophylaxis, so long as its caught within 24 hours, have a __% chance of effective prevention of the virus?
100%
Effectiveness of Post exposure prophylaxis drops __% in those treated within 72 hours rather than 24
52%!
At what point is someone not a candidate for post exposure prophylaxis?
if not treated within 72 hours of exposure
What is the key to maintaining and preventing the HIV virus?
Early Detection and Treatment (to decrease transmission and maintain health)
