HIV Slides 1-13: Intro Flashcards
How do retroviruses work?
Reverse transcriptase integrates viral RNA into host DNA - stays forever
What do viral oncogenes do?
Transform the host cell to express oncogenes, growth factors. Malignant transformation occurs.
What do host proto-oncogenes do?
Host non active genes that viral DNA activates to transform cells.
Leukemia or sarcoma viruses
What is HTLV1
Human T-cell leukemia
What is HTLV2?
Hairy T-cell leukemia
What is the origin of HIV?
Cross-species transmission of Simian Immunodeficiency virus (SIV)
How does HIV infect the cells?
Binds CD4 receptor on human t-lymphocytes (gp 120 and gp 41 on virus)
What proteins does the HIV virus code for?
Reverse transcriptase, integrase, and protease
What do viral encoded proteases do?
Cleave functional viral proteins from precursors
How many new virions are produced each day?
10^9
Infected T-cells have a half life of?
1.6 days
Time from release of new virion to infection of a new cell and release of another new virion is?
2.6 days
140 generations of virus each year
What are the goals of therapy for HIV?
Maximal and durable suppression of viral load (HIV RNA less than 50 copies per mL)
Reduction of HIV-related morbidity and mortality
Improvement of quality of life
Restoration of immunologic function
Prevent HIV transmission
What treatment considerations are there for HIV?
Resistance (6-16% to at least one drug class)
Tropism (CCR5 or CXCR4)
Contraindications (CD4 count/HLA typing)
Co-morbidities (Hepatitis)
Adherence potential (greater than 95%) - dosing frequency, number, size of pills, cost, food and fluid restrictions
Adverse drug reactions (Potential drug interactions and pregnancy)
In the first 2-4 weeks, what occurs to CD4+ cell count?
It decreases, then increases
In the first 6-10 years, what happens to CD4+ cell count?
It continues to decrease
In the last 2-3 years of HIV, what happens to CD4+ cell counts?
It continues to decrease
In the first 2-4 weeks, what happens to virus levels in the blood?
They increase to a peak, causing flu like symptoms
In the first 6-10 years, what happens to virus levels in the blood?
They decrease but stay at steady levels
In the last 2-3 years, what happens to virus levels in the blood?
They start to increase again,
What happens to anti-HIV antibody in the first 2-4 weeks?
They begin to increase when the HIV virus levels spike
What happens to anti-HIV antibody in the first 6-10 years?
They increase to a peak and stay steady
What happens to anti-HIV antibody in the last 2-3 years?
They start to decrease as virus levels increase
First skin and mucous membrane immune defects occur, then systemic immune deficiency
When do we treat HIV patients?
All HIV infected individuals should be treated regardless of CD4 count to reduce morbidity and mortality from HIV infections and prevent transmission by infected individuals.
What groups of patients require special attention with HIV treatment/
Pregnant women
Patients with HIV associated nephropathy, HIV associated dementia, or malignancies
Patients co-infected with HBV or HBC when treatment is indicated
All patients treated for HIV should receive what?
Genotypic drug resistance
HLA-B 5701 testing (hypersensitivity reaction with Abacavir)
Co-receptor tropism testing (prior to Maraviroc use; CCR5 changes to CXCR4 or mixed tropic with decreased CD 4 counts)
Plasma viral RNA load (at baseline and regular basis thereafter esp after changes in therapy)
What are the general treatment guidelines for HIV?
Two nucleoside reverse transcriptase inhibitors plus ONE of the following groups:
Non nucleoside reverse transcriptase inhibitor (2 NRTI + 1 NNRTI)
Protease inhibitor (boosted with Ritonavir) (2 NRTI + 1-2 PI)
Integrase stand transfer inhibitor based (2 NRTI + INSTI)
