HIV Flashcards
Origins of AIDS epidemic
- entered humans from chimps before 1930 in east central Africa
1996- HAART began with good outcomes
2003- global rollout of antiretrovirals
2014: 36.9 million adults/kids living with HIV–most in sub-saharan Africa (25.8 million) with South Africa having the highest prevalence
- more prevalent in certain subgroups in US
Markes of HIV dz
- CD4 lymphocyte count: as they are main host cell; correlates with disease progression
- Plasma HIV RNA level– measure of extent of ongoing replication in lymphoid tissue; copies per ml blood
want to see undetectable viral load–suggests minimal replication rate and low potential for developing resistance to drugs
How does HIV get into CD4 cell
- uses CD4 receptor and co-receptor, either CCR5 or CXCR4
- no current drug inhibiting CD4 binding but one in research
- have medication blocking CCR5 receptor. Virus mutates to use CXCR4 and are resistant to CCR5 blockers
Steps:
1) CD4 binding
2) gp120 conformational change and co-receptor binding
3) gp41 conformational change/fusion
CCR5 delta-32 mutation
natural polymorphism with 32 bp deletion in CCR5 gene– frame shift and protein truncation so that CCR5 not expressed on cell surface; relatively resistant to HIV or have more benign clinical course
Allele Distribution: seems to be most common in Caucasians both worldwide and in N America/Europe
~1% homozygosity in Caucasians
Primary HIV infection
- often associated with acute febrile illness, mono-like with or without aseptic meningitis
- usually 2-3 weeks after HIV exposure
- occurs in >50% pts but often unrecognized–maybe think just another viral illness
- if untreated, CD4 count is depleted; think about 1/3 or more new infections in acute period when ppl don’t know they are infected but have HUGE viral load
Signs/Sxs:
- fever, fatigue, maculopapular rash, myalgia, headache, pharyngitis, cervical nodes, arthralgia, oral ulcers, odynophagia, weight loss, diarrhea, oral candidiasis, photophobia
Risk of transmission
varies during infection course; Acute “early” pts perhaps responsible for lots of transmission
Natural Hx of HIV infection
acute illness, then if untreated CD4 count will drop, making you more likely to get certain opportunistic infections which occur at certain CD4 counts
Opportunistic infection
- infection that takes advantage of weakened immune system to cause an illness; see with HIV, chemo, glucocorticoid therapy
- many of these happen when CD4 low
Pneumocystic Pneumonia
(PCP) opportunistic infection;
diffuse infiltrate in lungs
Opportunistic infections in HIV
- Kaposi sarcoma– interaction between HIV and HHV-8; reddish-purple vascular tumors
- PCP
- Oral thrush
- CMV retinitis –infiltrate and hemorrhage around fovea– CD4 count
Targets for antiretroviral therapy
Entry inhibitors (target fusion or CCR5)
Reverse transcriptase inhibitors (NRTI-nucleosides/nucleotides– and NNRTIs)
- Integrase inhibitors
- Protease Inhibitors
Effects of Antiretroviral Therapy
Virologic/immunologic effect:
- potent inhibition of viral replication
- Early HIV: prevent immunologic deterioration
- Advanced HIV: allows immunologic recovery
Clinical effect:
- prevent opportunistic infections/improve existing ones
- reduce hospitalization, long term care facility use, meds for OIs, and cost
Factors contributing to HIV evolution
- genetic diversity (introduction of mutations–especially since RT is error prone)
- fast replication rate
- selective pressures (genetic bottle necks)
- A population of viruses exists in single infected person– “quasispecies”–genetically distinct viral variants evolve from initial virus inoculum
- variants due to error prone nature of viral replication
- quasispecies more closely related to each other than to virus in other infected persons
IMPORTANT TO ADHERE TO THERAPY TO AVOID RESISTANCE!
expected response to antiretroviral therapy
- reduce HIV-1 RNA, ideally to undetectable levels-if doesn’t happen in 1st month expect drug resistance or non-adherence
- increase CD4 lymphocyte count (may or may not happen in 1st month)
- improved existing opportunistic complications
- decreased morbidity/mortality
- reduced HIV transmission (sexually and to infants)
Pre-Exposure Prophylaxis
(PrEP)
- HIV negative person takes combination of HIV medications to prevent acquisition of HIV infection
- increased risk of HIV acquisition–maybe in relationship with HIV+, IV drug user, MSM, risky behavior
- take 2 drugs: tenofovir-emtricitabline
