HIV/AIDS Flashcards
target cell
The primary target cell of HIV is the CD4 T helper/inducer lymphocyte
HIV expresses receptor proteins (gp120) which preferentially bind to CD4 receptors on T cells, macrophages, and dendritic cells
CD4 cells are key component of cell-mediated immunity, and are responsible for assisting with antibody production and secreting cytokines to protect the host against bacterial and viral infections
Infected CD4 cells are impaired from normal functions, used by HIV for viral replication, and ultimately destroyed by a direct cytolytic effect
transmission
exposure of mucous membrane or damaged tissue to infected body fluids - not urine, feces, sweat or tears
blood-stream exposure to infected body fluids
mother to child
NOT spread by casual contct, spitting, sneezing/coughing, sharing food/utensils, insects, closed-mouth kissing, swimming pools
stages of infection
acute retroviral syndrome - chronic HIV infection (asymptomatic) - acquired immunodeficiency syndrome (AIDS) (symptomatic)
acute retroviral syndrome
seen in 2-6 after initial infection
characterized by non-specific self-limiting flu-like symptoms
chronic HIV infection
antibodies developed against HIV reduce virus in the serum
equilibrium (viral “set-point”) is reached 3-6 mo after initial infection
A higher “set-point” is correlated with greater risk for faster disease progression
at baseline, a patient has 800-1500 CD4 cells/mm^3
CD4 decline is fastest in 1st year, then progressive
this phase is generally asymptomatic and lasts 8-10 years w/out therapy
AIDS
profound immunosuppression - no longer able to ward off infectious processes
at CD4 less than 500, patients may develop throush, vulvovaginal candidiasis, oral hairy leukopenia, herpes zoster, bacterial penumonia and peripheral neuropathy
at CD4 less than 200, AIDS-defining opportunistic infections (OIs) can occur
who should be screened for HIV
patients aged 13-64 in any health care setting, all pregnant women as early as possible during each pregnancy, all patients treated for tuberculosis, all patient attending STD clinics during each visit for a new complaint
testing methods - dynamics of viremia after HIV infection
HIV RNA - 10 days after infection
p24 - 14-20 days but only transiently detectable
IgM antibodies - 10-13 days after HIV RNA is detectable
IgG antibodies are able to be picked up by all generations of testing 18-38 days after HIV RNA is detectable
diagnosis
either a positive result from a multitest algorithm or a positive virologic test
CD4 T lymphocyte cell count
used to assess overall immunocompetence
particularly useful before initiation of antiretroviral therapy
important for knowing if opportunistic infection prophylaxis should be initiated or discontinued
stage 1: over 500 cells, over 26%
stage 2: 200-499 cells, 14-25%
stage 3: (AIDS): under 200 cells, under 14%
HIV RNA
viral load
used to assess the effectiveness of therapy
most useful after the initiation of antiretroviral therapy
higher baseline viral loads are predictive of a patient’s rate of disease progression
pretreatment viral loads also play a role in the selection of drug regimens
staging disease
0, 1, 2, 3 (AIDS)
based on CD$ count
stage 0: early infection, established if a positive result is found within 180 days of a negative or intermediate result regardless of CD4 count
stage 3 (AIDS): established if an AIDS-defining opportunistic infection is diagnosed, regardless of CD4 count
NRTIs
form the backbone of initial antiretroviral therapy in treatment-naive patients
NRTI MOA
the HIV virus encodes an RNA-dependent DNA polymerase called reverse transcriptase
RT converts viral RNA into double stranded proviral DNA which is incorporated into the host cell genome
these agents are synthetic analogues of purine and pyrimidine and must undergo intracellular phosphorylation - enzymes responsible are dependent upon the nucleoside mimicked
-adenosine - tenofovir, didanosine
-cytidine - lamivudine and emtrictabine
-thymidine - stavudine and zidovudine
-guanosine - abacavir
most need to be triphosphorylated (except tenofovir which only requires 2 phosphorylations)
phosphorylated NRTIs compete with native nucleotides for incorporation into growing proviral DNA chain but elongation terminates due to lack of 3’-OH group
NRTI AEs
class effects: mitochondrial toxicity and lactic acidosis with or without hepatomegaly and hepatic steatosis - host cell DNA polymerases can also be inhibited by these agents
prior to abacavir therapy, patient must be screened for HLA-B*5701 (positive = fatal hypersensitivity)
abacavir may have increased risk of MI
TDF has been associated with new onset or worsening renal impairment and decreases in bone mineral density
TAF is a novel oral prodrug of TVF which is more stable and has increased safety profile in terms of renal impairment and BMD
NRTI precautions and interactions
most NRTIs are renally eliminated; zidovudine and abacavir are cleared hepatically all NRTIs (except abacavir) require dosage adjustment in renal insufficiency few clinically significant drug interactions exist
NNRTI MOA
bind an allosteric site of the RT inducing a conformational change which results in reduced functionality of the enzyme - noncompetitive with NRTIs
NNRTI AEs
class effects: rash (usually mild; SJS has been reported)
NNRTI precautions and interactions
eliminated hepatically
many significant drug interactions exist
high-level resistance develops easily and quickly to agents in the class
protease inhibitors MOA
competitively inhibit the action of viral protease, the enzyme responsible for cleavage of precursor polypeptides into functional structural and enzymatic viral proteins
prevents the assembly, maturation and release of new infectious virions
PI AEs
Class effects: GI intolerance including nausea, vomiting and diarrhea; insulin resistance and lipodystrophy
PI precautions and interactions
all except nelfinavir undergo hepatic metabolism via CYP3A4 and are not recommended in severe hepatic impairment
many, many drug interactions
boosting: ritonavir is a potent inhibitor of CYP3A4 with anti-HIV activity seen at doses of 600 mg BID; clinically its used exclusively at low doses to boost the conc of other coadministered PIs - boosted PIs are characterized by a highly favorable resistance profile but greater pill burden
integrase strand transfer inhibitors MOA
inhibit the HIV integrase enzyme preventing the proviral DNA integration into the host cell genome
INSTIs AEs
generally well tolerated
