HIV and AIDS Flashcards
Define HIV
Enzyme-linked immunosorbent assay (ELISA) and Western blot positive
Define AIDS
- CD4+ cell count that is, or every has been, less the 200 cells/mm3
- HIV seropositive and a diagnosis of an AIDS-defining illness (ADI)
- Tuberculosis
- Kaposi sarcoma
- Non-Hodkin lymphoma
- P. jiroveci
- Toxoplasmosis
- Crptococcal meningitis
- Mycobacterium avium
- Cytomegalovirus
Perinatal/Vertical transmission of HIV
- about 25% risk
- oral zidovudine at 13-14 weeks gestation (mom)
- zidovudine intravenous loa and infusion during labor and delivery (mom)
- oral zidovudine for first 6-8 weeks of life (neonate)
- usually zidovudine is prescribed as a component of three-drug antiretroviral regimen, reducing risk to less than 1%
- elective cesarian section: viral load greater than 1000 copies/ml
Conversion Syndrome
1) Occurs within days to weeks after initial infection
2) High viral load
3) Fever, rash, fatigue, malaise, lymphadenopathy
Screening for HIV
1) anual screening for all Americans 13-64 years of age
2) OraQuick Advantage HIV-1 and HIV-2
- 20 minute rapid test
- approved for over-the-counter status
3) HIV ELISA
- enzyme linked immunosorbent assay
- high sensitivity
4) Western blot
- high specificity
- cost
Antiretrovirals
1) Nucleoside reverse transcriptase inhibitors (NRTIs)
2) Nucleotide reverse transcriptase inhibitors
3) Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
4) Protease inhibitors (PIs)
5) Fusion inhibitors
6) Coreceptor antagonists
7) Integrase inhibitors
Treatment principles for HIV
1) Monotherapy is never appropriate (except in certain extenuating cases involving pregnancy)
2) Standard of care consists of three concurrent antiretrovirals
3) Resistance testing is indicated in treatment-naive patients initiating therapy and in treatment failure.
Treatment failure: Inability to achieve undetectable viral load (less than 48 copies/mL) at 24 weeks o presence of a viremia in a patient who had previously achieved an undetectable viral load.
4) Primary goal is undetectable viral load, Secondary goal is an increase CD4+ cell count.
5) Therapy is lifelong, and it requires strict adherence
6) For drug toxicity, it is acceptable to exchange a substitute frug from the same class as the offending agent without altering the entire antiretroviral regimen.
7) Salvage therapy: Use of unconventional antiretroviral combinations in an effort to achieve an undetectable viral load (usually in treament-experience patients)
8) Current treatment may reduce infectivity, but is never curative
General principles of resistance testing in HIV
1) Costly and time-consuming
2) Sometimes difficult to interpret
3) Requires a viral load of at least 1000 copies/mL to be performed
4) Patients should continue on failing antiretroviral regimens while testing is performed
Genotype resistance testing in HIV
1) Analysis of viral genetic mutations known to be associated with resistance to particular antiretrovirals
2) Preferred testing modality early in the course of the disease (naive patients)
3) Less costly and quicker turnaround compared with phenotypic assays
4) Provides resistance or susceptible data and associated mutation present
5) May become particularly difficult to interpret when several mutations are present.
Phenotype resistance testing in HIV
1) Measure of direct susceptibility, which requires viral culture
2) Preferred testing modality in treatment-experienced patients
3) More costly and time-consuming than genotyping
4) May account for “mixtures” of mutations that are synergistic or antagonistic
Guidelines for initiating HIV therapy
1) initiate therapy in all patietns with an ADI or a CD4+ count less than 500 cells/mm3
2) Initiate therapy (regardless of CD4+) in patients who are pregnant, have HIV nephropathy, or have hepatitis B confection (when hepatitis B treatment is indicated)
3) Treatment is recommended for patients with a CD4+ count between 350 and 500 cells/mm3
4) In patients with a CD4+ count >500 cells/mm3, the panel was split 50:50 to treat or make treatment optional
5) Patients and/or providers may choose to defer or initiate therapy on a case-by-case basis
Preferred antiretroviral combinations for initiating therapy
1) Two NRTIs plus one NNRTI: Tenofovir plus emtricitabine plus efavirenz
2) Two NRTIs plus one PI
- Tenofovir plus emtricitabine plus ritonavir-boosted atazanavir
- Tenofovir plus emtricitabine plus darunavir
3) Two NRTIs plus one integrate inhibitor
- Tenofovir plus emtricitabine plus raltegravir
Other considerations in initiating therapy in HIV
1) Monotherapy should be avoided (although in unusual circumstances, zidovudine may be employed
2) Dual and triple NRTI regimens should be avoided
3) Efavirenz should not be employed during pregnancy in the first trimester or in women of childbearing potential who are not on adequate contraception
4) Nevirapine should not be initiated in treatment naive women with CD4+ greater than 250 cells/mm3 or in men the CD4+ cell counts greater than 400 cell/mm3
5) Zidovudine and stavudine should not be combined secondary to the risk of drug-drug antagonism
Vaccinations in HIV
- No live vaccines
- varicella unless CD4+ cell count >200
- zoster unless CD4+ cell coung >200
- intranasal influenza
- Inactivated vaccines may be administered
- Specially indicated:
- Hepatitis A (MSM)
- Hepatitis B
- Pneumococcal (every 5 years)
- Tdap (once during adulthood and then tetanus and diptheria (Td) every 10 years)
- Influenza (inactivated form yearly)
Tuberculosis (TB) Screening in HIV
1) Mantoux test (purifited protein derivative (PPD) of tuberculin
2) Yearly screening
3) Read in 48-72 hours
4) Positive test (greater than 5mm) - follow up with chest radiograph
5) Blood-based assays: QuantiFERON-TB may be used instead of PPD
NRTI - Zidovudine
- anemia
- not to be combined with stavudine
NRTI- Didanosine EC
- do not crush or chew
- peripheral neuropathy
- pancreatitis
NRTI - Lamivudine
- relatively benign adverse effect profile
- activity against hepatitis B
NRTI - Emtricitabine
- lamivudine analogue with a long half-life, once-daily dosing
- activity against hepatitis B
NRTI - Abacavir
- hypersensitivity reactions (rash, shortness of breath
- HLA_B*5701 screening (positive test precludes drug use
NRTI - Tenofovir
- often classified with the NRTIs
- nephrotoxicity
- activity against hepatitis B
NNRTI - Nevirapine
- low resistance ceiling
- dosing tiration reduces incidence of rash
- risk of hepatitis (based on sex an CD4* cell count)
NNRTI - Efavirenz
- bedtime dosing to avoid “central nervous sytem (CNS) disengagement” and dizziness
- nightmares and vivid dreams
- avoid in patients with substance abuse or psychiatric diseases such as depression
- avoid in pregnancy and in women of childbearing potential
NNRTI - Etravirine
“Second-generation” NNRTI with higher resistance ceiling and twice-daily dosing
