HIV/AIDS Flashcards
Retrovirus
An RNA virus that replicates by inserting a DNA copy of their genome into the host cell
HIV structure
- Enveloped RNA retrovirus
- Capsid: core that contains the RNA ( med research on interference with capsid)
- Enzymes in the capsid carry out steps in the life cycle
- Glycoproteins: spikes embedded in the envelope - they have an affinity for binding on CD4 receptors
Steps of viral replication
- HIV binds to CD4 cell. RNA, proteins & enzymes released
- HIV reverse transcriptase converts viral RNA into DNA.
- HIV DNA moves to nucleus & spliced into host’s DNA.
- HIV RNA moves out of the nucleus into cytoplasm & makes long chains of viral proteins & enzymes.
- Immature viral particle forms containing cellular & HIV proteins. Chains cut into smaller pieces by protease.
- Infectious viral particle ready to be released containing HIV RNA, viral proteins & enzymes.
* *produce billions of new virus particles which can stay latent in the host DNA – undetectable unless they’re actively replicating
* *copies “seed”: disseminate w/o detection
HIV and CD4 cells
- Helper (CD4) cells coordinate & activate both B lymphocytes [antibody mediated] & cell-killing cytotoxic (CD8) lymphocytes [cell mediated]
- Cell-mediated immune response copes with microbes located within cells.
- HIV infects & destroys CD4 cells
- Loss of cells leads to immune system collapse & HIV disease.
- Decline in CD4 cells is used as a marker of the progression of HIV.
HIV and CD8 cells
- Important in initial immune response to HIV & at latent stage
- Kill infected cells that are producing virus
- Secrete soluble factors that suppress HIV replication: block by occupying receptors necessary for the entry of certain strains of HIV into the target cell
- New information shows two new strains of the HIV virus that target CD8 cells
HIV Immune function effects
- CD4 cell: decreased lymphokine production loss of stimulus for t and b activation
- CD8 cell: impaired cytotoxic activity; impaired feedback
- Macrophages: decreased phagocytosis, less IL-1 production, impaired antigen presentation
- B cells: diminished AB production
ALL THIS leads to increased susceptibility to opportunistic infection
HIV replication and mutation
Replication rate
Billions per day
99% of HIV in blood is from newly infected cells
30% of HIV in plasma replaced daily
Entire HIV population turnover Q14 days
High mutation rate
1 in 3 replication cycles: 3300 mutant viruses per day
½-life = 1-2 days
Extensive seeding occurs early in disease
“Sanctuary sites”
Dendritic cells of lymph nodes & glial cells of the CNS
HIV transported to CNS via macrophages: body doesn’t detect it
Transmissible body fluids
Blood Semen Vaginal secretions Breast milk Cerebral spinal fluid Synovial fluid Pleural & amniotic fluid
Transmission
- Unprotected sex-oral, anal (more risky), vaginal
- Blood to blood-sharing needles, occupational exposure, fighting, tattooing, body piercing, transfusions
- Mother to newborn-in utero, childbirth, breast feeding
Risk factors
Sexual activity
Injection drug use
Recipients of blood products (1975-March 1985)
Hemophiliacs who received pooled plasma
Children of HIV-infected women
30% will be infected w/o Treatment
Breastfeeding is a possible route of transmission
Prenatal, intrapartum & postpartum AZT significantly decreases risk of HIV transmission from mother to child (29% to 2%)
Needlestick
Post-exposure treatment with zidovudine (Retrovir)
Transmission risk r/t activities
Receptive anal intercourse: 1/100 – 1/300
Insertive anal intercourse: 1/1000
Receptive vaginal intercourse: 1/1000
Insertive vaginal intercourse: 1/10,000
Receptive fellatio with ejaculation: 1/1000
Needlestick with infected blood: 1/300
Illicit drug use with needle sharing: 1/150
HIV infected blood donor: 95%
Screened blood (viral load testing): 1/1,000,000
HIV infected mother: 2%-40%
Factors that Increase risk
- Acute infection, roughly the 12 weeks after contracting HIV, can increase transmission likelihood 26 times, raising a 1.43% risk to 37%—higher than 1 in 3. This is because viral load skyrockets during the acute phase.
- Presence of other sexually transmitted infections (STIs) can amplify risk by as much as 8 times.
- Exposure to gender inequality and intimate partner violence can raise a woman’s HIV risk 1.5 times.
Factors that decrease risk
- Circumcision can lower heterosexual men’s risk by 60%.
- Treatment as prevention, TasP, when HIV-positive people on meds maintain an undetectable viral load, can reduce transmission risk by 96%. Some research hints that the number may approach 100%.
- Pre-exposure prophylaxis, PrEP, when HIV-negative people take daily med Truvada, can decrease risk by upwards of 92%, depending on adherence. Post-exposure prophylaxis, PEP, works similarly.
- Condoms, according to the CDC, lower risk on average by 80%.
- Forms of seroadaptation, such as having condomless sex only with people of your same sero status, can also lower risk, but the outcomes vary.
HIV testing
DNA HIV - Viral nucleic acid tests (12 days)
- Polymerase Chain Reaction (PCR)
- Nucleic acid sequence-based amplification
- Branched chain DNA tests
Viral Culture
- Highly specific but negative result meaningless
- Not frequently used to diagnose HIV
Immunofluorescence Antibody Testing
- Alternative to Western Blot for confirmation of HIV infection
Urine & Saliva Serologic Testing
- Urine EIA
- Saliva EIA
- Rapid Enzyme EIA
Home Testing: Fingerstick specimen sent to a laboratory
ELISA testing
Screener test
Enzyme Linked ImmunoSorbent assay (ELISA) determines response of antibodies to HIV virus
Used in children older than 18 months
High sensitivity but low specificity: many false positives
Western blot test
Confirms the presence of HIV antibodies
Useful in children older than 18 months of age
A positive HIV antibody test in children younger than 18 months of age indicates only that the mother is infected
More specific for HIV
P24 antigen test
Indicates active replication
- Used to detect HIV antigen in children younger than 18 months
- Test can be useful at any age
- Only a positive result is significant
- Two or more positive results are diagnostic for HIV infection
CD4+ test
Used to assess immune status, risk for disease progression, and need for PCP prophylaxis
+ Absolute CD4 count: Predictor of HIV progression - Monitor Immune Function
- incr. risk infection/malignancy if CD4<200 cells/mcL
+ CD4 Percentage count:
- Predictor of HIV progression
- Monitor Immune Function
- Incr. risk infection/malignancy if CD4<200 cells/mcL
Home HIV tests
Home Access HIV-1 Test system
Involves pricking one’s finger to collect blood and sending to lab. Anonymous. Manufacturer provides confidential counseling and referral for treatment.
OraQuick In-Home HIV Test
Involves swabbing mouth and using a kit in the home to test. Results in 20 min. If positive, need follow-up test. Counseling and referral included. Some false neg.
Lab criteria for diagnosis
Positive result from an HIV antibody screening test (e.g., ELISA) confirmed by a positive result from a supplemental HIV antibody test (e.g., Western blot)
OR
Positive result or report of a detectable quantity from any of the following HIV virologic (i.e., non-antibody) tests:
- HIV nucleic acid (DNA or RNA) detection test (e.g., polymerase chain reaction [PCR])
- HIV p24 antigen test, including neutralization assay
- HIV isolation (viral culture)
HIV S&S
\+Acute Infection -Mononucleosis-like syndrome -Fever -Rash -Myalgia -Malaise Self-limited syndrome lasting ~6-8 weeks post-infection Associated with development of HIV antibody
+ Asymptomatic Infection
Follows initial infection
Variable duration
+ Persistent Generalized Lymphadenopathy
Lymph node enlargement 1 cm or greater in two or more extra-inguinal sites
Adenopathy persists longer than 3 months
HIV Staging
Stage 1
- No AIDS-defining condition and either
- CD4+ T-lymphocyte count of >500 cells/mcL or
- CD4+ T-lymphocyte percentage of total lymphocytes of >29%
Stage 2
- No AIDS-defining condition and either
- CD4+ T-lymphocyte count of 200–499 cells/mcL or
- CD4+ T-lymphocyte percentage of total lymphocytes of 14 - 28%
Stage 3 (AIDS)
- CD4+ T-lymphocyte count of <200 cells/mcL or
- CD4+ T-lymphocyte percentage of total lymphocytes of <14% or documentation of an AIDS-defining condition
- Documentation of an AIDS-defining condition supersedes a CD4+ Tcell count of >200 cells/mcL and a CD4+ T-lymphocyte percentage of total lymphocytes of >14%
HIV disease spectrum
1-3 months; HIV infections w/ flu-like symptoms 1-10+ years: Asymptomatic: No symptoms Symptomatic: Fatigue Diarrhea Fever Thrush Skin rash Weight loss Swollen glands
Drug resistance testing
Genotypic Assays (done first, inform treatment decisions): Detect drug resistance mutations present in relevant viral genes
Phenotypic Assays (if genotypic treatment fails): Measure the ability of a virus to grow in different concentrations of antiretroviral drugs
____________________________
- Recommended for persons with HIV infection when they enter into care regardless of whether therapy will be initiated immediately
- If therapy is deferred, repeat testing at the time of antiretroviral therapy initiation should be considered
- A genotypic assay is generally preferred for antiretroviral-naïve persons
- HIV drug resistance testing should be performed to assist in the selection of active drugs when changing antiretroviral regimens
- Genotypic resistance testing is recommended for all pregnant women prior to initiation of therapy and for those entering pregnancy with detectable HIV RNA levels while on therapy
