Podcast
Questions and Answers
What is the primary target for the binding of the HIV envelope protein gp160?
What is the primary target for the binding of the HIV envelope protein gp160?
- CD4 receptor (correct)
- CCR5 coreceptor
- CXCR4 coreceptor
- Macrophage lineage cells
Which of the following agents is NOT classified as an antiretroviral treatment for HIV?
Which of the following agents is NOT classified as an antiretroviral treatment for HIV?
- Nonnucleoside Reverse Transcriptase Inhibitors
- HIV Protease Inhibitors
- Antihypertensive medications (correct)
- Integrase inhibitors
What role does CCR5 and CXCR4 play in the HIV life cycle?
What role does CCR5 and CXCR4 play in the HIV life cycle?
- They act as viral envelope proteins.
- They inhibit HIV infection.
- They serve as primary receptors for virus entry. (correct)
- They are targets for virus replication.
Why is understanding the HIV life cycle important in therapy?
Why is understanding the HIV life cycle important in therapy?
Which statement about the current status of HIV treatment is accurate?
Which statement about the current status of HIV treatment is accurate?
What is primarily responsible for the emergence of permanent drug resistance in HIV treatment?
What is primarily responsible for the emergence of permanent drug resistance in HIV treatment?
What signal indicates a shift from CCR5 to CXCR4 in HIV-infected individuals?
What signal indicates a shift from CCR5 to CXCR4 in HIV-infected individuals?
What role does the gp41 domain of env serve in the HIV life cycle?
What role does the gp41 domain of env serve in the HIV life cycle?
Which of the following statements about HIV pathogenesis is correct?
Which of the following statements about HIV pathogenesis is correct?
What is the significance of the coreceptor switch from CCR5 to CXCR4 in HIV infections?
What is the significance of the coreceptor switch from CCR5 to CXCR4 in HIV infections?
What is the role of the env gene in the HIV virus?
What is the role of the env gene in the HIV virus?
Which viral protein is responsible for combating host defenses?
Which viral protein is responsible for combating host defenses?
What happens to the CD4+ T-lymphocyte count after an initial HIV infection?
What happens to the CD4+ T-lymphocyte count after an initial HIV infection?
How long is the median time from CCR5-tropic HIV-1 infection to clinical AIDS if untreated?
How long is the median time from CCR5-tropic HIV-1 infection to clinical AIDS if untreated?
What crisis point occurs when the peripheral CD4 count falls below 200 cells/mm3?
What crisis point occurs when the peripheral CD4 count falls below 200 cells/mm3?
What is the relationship between HIV RNA concentration and CD4+ T-lymphocyte count during HIV infection?
What is the relationship between HIV RNA concentration and CD4+ T-lymphocyte count during HIV infection?
Which small genes in HIV are responsible for enhancing virion production?
Which small genes in HIV are responsible for enhancing virion production?
What is a characteristic of HIV's reverse transcriptase?
What is a characteristic of HIV's reverse transcriptase?
Which subtype of HIV is primarily associated with the global epidemic?
Which subtype of HIV is primarily associated with the global epidemic?
How frequently does mutation occur during full-length replication of HIV?
How frequently does mutation occur during full-length replication of HIV?
What role does viral integrase play in the HIV life cycle?
What role does viral integrase play in the HIV life cycle?
What is a unique feature of the HIV genome's structure?
What is a unique feature of the HIV genome's structure?
Which type of drugs are HIV-2 specifically resistant to?
Which type of drugs are HIV-2 specifically resistant to?
Where is the structural protein assembly concentrated in the HIV life cycle?
Where is the structural protein assembly concentrated in the HIV life cycle?
Following integration into the host chromosome, what can occur with the HIV virus?
Following integration into the host chromosome, what can occur with the HIV virus?
Study Notes
Antiretroviral Agents and Treatment of HIV Infection
- Pathogenesis of HIV-Related Disease: HIV is a lentivirus, a retrovirus that establishes a chronic persistent infection, with gradual symptom onset. Virus replication is constant after infection. There's no true latency period. Humans and non-human primates are the only natural hosts.
- Two major families of HIV exist: HIV-1 and HIV-2. HIV-1 is mostly responsible for the global epidemic. HIV-2 is more closely related to SIV and common in western Africa. HIV-1 has genetic diversity, with five subfamilies or clades. NNRTIs are specific to HIV-1.
- Virus Structure: HIV is a retrovirus with a small RNA genome of 9300 base pairs. It has two copies of the genome within a nucleocapsid core, surrounded by a lipid bilayer (envelope) derived from the host cell. The genome encodes gag (structural proteins), pol (reverse transcriptase, protease, and integrase), and env (envelope protein for cell attachment and entry). These regulatory proteins include tat, rev, nef, and vp.
- Virus Life Cycle: The envelope protein gp160 controls HIV tropism(target cell binding). The main target is the CD4 receptor on lymphocytes and macrophages, but co-receptors CCR5 and CXCR4 are also required for entry. CCR5-tropic infections are the most common. A shift to CXCR4 tropism is associated with disease progression. gp41 domain of env controls the viral lipid bilayer's fusion with the host cell. Viral RNA enters the cytoplasm, replicated into DNA, and integrated into a host chromosome by the viral integrase. Reverse transcriptase is error-prone, leading to frequent mutations, occurring at about three times per replication.
- How the Virus Causes Disease: HIV infection is likely initiated by one or a few infectious particles. After infection, there's a rapid burst of replication (peak at 2 - 4 weeks), reaching 10⁶ CD4+ cells. Subsequent host immune responses decrease infectious virions in plasma, reaching a set point. The average infected individual produces billions of infectious particles daily. A steady decline in CD4+ T lymphocyte count and an increase in plasma HIV RNA concentration happen over time, leading to a higher risk of opportunistic diseases, and ultimately, death.
- Principles of HIV Chemotherapy: Current treatment focuses on suppressing viral replication to prevent drug resistance. A standard care regimen involves three antiretroviral drugs simultaneously during initiation of treatment, and two to three drugs afterward. Initiating therapy regardless of baseline CD4 count is the current global standard (based on randomised clinical trials). Treatment is for life to control virus replication.
Principles of HIV Chemotherapy
- Drug resistance is a significant challenge. Untreated patients frequently harbor viruses with resistance mutations.
- Drug regimens usually need to contain a combination of multiple drugs to prevent resistance.
- A successful therapy goal is an undetectable viral load (≤50 copies/mL).
- Breaks in treatment increase resistance risk and disease progression. Long-term toxicity of drugs is important to consider.
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