1) Dx of HIV -
- Traditional - ELISA screening -> Western bot
- Now - 2 positive immunologic tests that are orthogonal ( different antigens or principles )
- Ag/Ab test followed by Ab ONLY test
- Ab test -> viral load assay
- RAPID Ab test -> conventional immunoassay
- A single non antibodies test ( p24, viral load ) is also diagnostic
2) Monitoring - viral load is better
3) Inclusion of stage 0
- Indicate very early infection, when seroconversion is taking place
- A sequence of discordant test results indicative of early HIV infection in which a negative or indeterminate result was within 180 days of a positive result
- Negative or indeterminate ab, ab/ag or NAT within 6 months BEFORE a positive test of any type or
- Positive test of viral specific markers within 6 mths of a negative / indeterminate antibody type
- If > 180 days after stage 0 has been diagnosed, the stage is classified at stage 1,2,3 or unknown
- Exception - stage 0 is NOT diagnosed if the negative / indeterminate HIV test was preceded > 60 days by a confirmed positive HIV test, a clinical dx of HIV, CD4 or opportunistic infection indicative of stage 3 infection
HIV and TB
1) Look out for 4 sxs of TB - fever, cough, night sweats and LOW - absence of 4 combos have high NPV
2) LTBI = TST/IGRA +ve but CXR and smear negative
- Daily INH for 9 months
3) TB tx in HIV
- EHRZ DAILY instead of 3X weekly
- Bactrim prophylaxis ( protect against toxoplasmosis and PCP ), at least for 6 months
4) When to start ART in TB
A new RCT suggests starting ART early in CD4 > 220 does not give any advantage over late ART
5) DIH ( Drug induced hepatitis )
- Dx if
- Sxs + AST/ALT > 3X ULN
- No Sxs + AST/ALT > 5X ULN
- Hepatotoxic anti TB drugs - INH and pyrazinamide are the most potent
- Less - rifampin
- Least - ethambutol, streptomycin and FQ
6) Options to DIH
- Stop it - if patient has less bacilli burden
- Change to SEF ( least toxic ) combination if high bacilli burden ( disseminated, miliary or cavitation )
7) Overlapping toxicities
- Notice that NNRTIs have many overlapped toxicities with anti TB drugs
- Basically ALL ARV drugs are hepatotoxic
Change of HAART
1) Efavirenz
- Avoid in people working in night shifts
- Avoid in depression
2) Tenofovir - avoid in kidney disease, osteoporosis
Zidovudine - can cause macrocytic anemia, so avoid in anemia
Abacavir - avoid in heart disease
3) Avoid NVP and abacavir in very high viral load ( > 100,000 )
4) Tx failure - ask about adherence and potential side effects ( reasons of stopping )
5) Efavirenz and Nevirapine can BOTH cause rash
6) Algorithm
7) Early vs late switch
- Less resistance developed in early switch, but more pricey
- More resistance in late switch, but cheaper
8) NNRTI resistance is more common
- Takes longer time to peak, so virus has time to adapt
9) NRTI resistance - common in 3TC based regimen ( + AZT or TNF )
- NRTIs are structurally similar to purines and pyrimidines, so RT will not be able to differentiate between NRTIs and their natural counterparts -> so is incorporated into the synthesis of viral DNA -> NRTIs prevent the elongation of the DNA chain
- Resistance can develop when the RT has reduced ability to incorporate the drug
HIV and CNS
1) HIV is neutropic drug
2) Toxoplasmosis can present with focal CNS lesions or encephalitis
- IgM is not useful is dx, 90% is IgG
- Rx and evaluate response after 2 weeks
- Prophylaxis - Bactrim
3) Cryptococcosis
- Rx - liposomal amphotericin B + flucytosine and maintenance by fluconazole untol CSF fungal C and S is negative
- For high ICP, repeat LP or CSF shunt ( mannitol/ steroids NOT effective )
4) Timing of HAART after OI
Drug-drug interactions
1) Important rxns to note
- CYP 3A4
- Inducers - NVP, EFV
- Inhibitors - PIs ( Ritonavir ) - CYP 1A2
- INDUCED by ritonavir - CYP 2C19
- INDUCED by ritonavir
Ritonavir INHIBITS CYP 3A4 but INDUCES other CYPs
2) AZT and d4T not to be used tgt - binding competition
3) AZT and ganciclovir NOT to be used tgt - bone marrow toxicity
4) Important DDIs
Credit to all the people that prepare these nice and beautiful figures !!
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