Chapter 24: Laboratory Diagnosis of HIV Infection Flashcards
What is HIV?
○ Human immunodeficiency virus
○ the etiologic agent of the acquired immunodeficiency syndrome, or AIDS
What are the 3 major routes of HIV transmission?
○ Intimate sexual contact
○ Contact with blood or other bodily fluids
○ perinatally, from infected mother to infant
What is HIV classified as?
○ A retrovirus
○ contains ribonucleic acid (RNA) as its nucleic acid
What are the 2 serogroups of HIV?
HIV-1 and HIV-2
Of the 2 serogroups of HIV which is the most predominant?
HIV-1
How many subtypes of HIV-1 are there and what are they? Which is the major one?
○ 4 subtypes
○ M,N,O,P
○ M is the major subtype
Where is HIV-2 limited to?
West Africa- hence why there are fewer cases
What is a retrovirus?
○ Contains two copies of ssRNA
○ Reverse transcriptase transcribes the viral RNA into DNA
What are the main structural genes of HIV?
Gag, env, pol
What is the first step in HIV reproduction?
○ attachment of the virus to a susceptible host cell
○ mediated through the host-cell CD4 antigen
What is a provirus?
○ When the viral DNA becomes integrated into the host cell’s genome
○ Done through enzyme reverse transcriptase
When are viral genes expressed?
when the infected host cell is activated by binding to antigen or by exposure to cytokines
Viral DNA within the cell nucleus is then transcribed into what?
genomic RNA and messenger RNA (mRNA)
Why are genetic mutations common with viral replication?
Viral replication is very rapid and the reverse transcriptase enzyme lacks of proofreading
viral replication can be detected in the laboratory by?
presence of increased levels of p24 antigen and viral RNA in the host’s bloodstream
How is the lymphocytes response stimulated?
As the virus replicates, some of the viral proteins produced within host cells form complexes with MHC class I antigens
Where are the first antibodies directed at?
○ gag proteins such as p24
○ followed by production of antibodies to the envelope, pol, and regulatory proteins
How long are antibodies directed against virus detected?
6 weeks after infection
What seen weeks after initial infection? When HIV amount declines?
CD8+ cytotoxic T lymphocytes, also known as cytolytic T cells (CTLs)
Can HIV be eliminated completely?
No it can only be reduced due to its numerous escape methods
How are CTLs and antibodies hindered in response to HIV?
The rapid mutations of HIV
What can HIV be harbored as in the body for long periods of time?
○ Silent provirus
○ In this state it’s protected from immune attacks
What cells are affected in HIV infection?
CD4 and T helper cells are rendered nonfunctional
Aside from reducing numbers of T helper cells, what else does HIV do to T Helper?
○ causes abnormalities in T helper cell function
○ impairment of memory T helper cell responses
What are the stages of HIV infection?
○ Primary (Acute)
○ Latent period
○ AIDs
HIV Primary (Acute) stage
○ high levels of circulating virus begins to disseminate to the lymphoid organs
○ symptoms that resemble influenza or infectious mononucleosis
How long can the latent period of HIV infection last?
clinical latency may vary in length, with a median length of 10 years
What is AIDS?
○ the final stage of HIV infection
○ characterized by: profound immunosuppression, a resurgence of viremia, and life threatening infections and malignancies
Antiretroviral Therapy (ART)
○ Drugs that block various steps of the HIV replication cycle
○ Have significantly improved morbidity and mortality of HIV-infected persons
○ reduced the rate of perinatal transmission
What classifies a HIV infected person with having AIDS?
○ they have an absolute CD4 T lymphocyte count of less than 200/μL
○ or certain opportunistic infections or malignancies indicative of AIDS
What does the treatment of HIV involve?
supportive care of the infections and malignancies
○ administration of antiretroviral drugs to suppress the virus’s replication
Why is developing and HIV vaccine so tough?
○ ability of HIV to rapidly mutate and escape immune recognition
○ capability of HIV to persist despite vigorous immune responses
○ genetic variability in HIV clades
○ need to induce potent CTL and antibody responses
○ lack of an ideal animal model
What plays a key role in evaluating the degree of immune suppression?
CDC criteria utilize CD4 T-cell counts to classify patients into various stages of HIV
○ CD4 T-cell counts are used routinely to monitor the effectiveness of antiretroviral therapy
When should ART be initiated?
○ CD4 T-cell count is less than 350/μL
○ therapy should be changed if CD4 T-cell counts decline more than 25 percent
What is the gold standard for counting CD4 T-cells?
immunophenotyping with data analysis by flow cytometry
When should CD4 T-cells be performed?
every 3–6 months
What is the normal standard method for testing for HIV?
ELISA with confirmation with Western Blot
What can cause false negatives with ELISA?
○ collection of the sample prior to seroconversion
○ administration of immunosuppressive therapy or replacement transfusion
○ conditions of defective antibody synthesis
○ technical errors attributed to improper handling
What can cause false positives with ELISA?
○ heat inactivation of serum prior to testing
○ repeated freezing/thawing of specimens
○ presence of autoreactive antibodies
○ multiple pregnancies
○ severe hepatic disease
○ passive immunoglobulin administration
○ recent exposure to certain vaccines
○ certain malignancies
If an ELISA has a positive result what should be done afterward?
○ ELISA test should be repeated
○ 2/3 specimens are positive confirm with western blot
What about the Western Blot is beneficial but taxing?
This technique is more technically demanding than ELISA
○ but can provide an antibody profile of the patient sample that reveals the specificities to individual HIV antigens present
What is a positive result of a Western Blot?
○ positive control should be reactive with p24, gp41, gp120/160
○ Or at least two of these three bands
Viral Load Assay
○ Quantitative tests for HIV nucleic acid
○ based on amplification methods
○ play an essential role in helping physicians determine when to initiate antiretroviral therapy
What is the goal of HIV therapy?
to reach undetectable levels of HIV RNA (i.e., 50–80 copies/mL)
When should HIV RNA testing be done? According to the U.S. Department of Health and Human Services.
HIV RNA testing be performed before antiretroviral therapy begins, to obtain a baseline value
What isn’t a reliable test for HIV?
serological tests are not reliable in detecting HIV infection in children younger than 18 months
How can infants be tested for HIV?
Molecular methods
