To keep the momentum going, let’s move on to transmitted drug resistance. For those just joining, we previously discussed that #HIVDrugResistance is important yet challenging for learners.
2/ We also reviewed the basic principle that HIV resistance develops when HIV replicates in the setting of subtherapeutic drug levels. Virions containing resistance mutations are selected for in this case.
3/ Today we’ll define transmitted drug resistance (TDR) (vs acquired drug resistance). TDR = acquisition of drug-resistant HIV at the time of new HIV infection. We identify TDR when we do a baseline HIV genotype (recommended for all patients who are newly diagnosed with HIV).
4/ Interestingly, as @PaulSaxMD points out, a baseline HIV genotype (to detect TDR) is a nice to know but not a need to know piece of info. With same day ART starts, we start patients on therapy before we know the results of their HIV genotype.
5/ We can get away with this because we use INSTI-containing regimens for all of our 1st line therapy. Rates of TDR impacting our 1st line therapies are exceedingly uncommon. (1st line recommended regimens in the US summarized by @febrilepodcast below).
6/ Lucky for me, a nice updated on TDR just came out in CID. Rates of TDR in the US between 2014-2018 are shown below. doi.org/10.1093/cid/ci…
7/ The most common mutation detected was the K103N (8.6%). M184V (0.9%) & K65R (0.1%), less common. We will discuss these mores when we get into specific mutations. Should clarify this data is specific to US; global TDR beyond scope here.
8/ Transmitted drug resistance is very difficult if not impossible to predict. Acquired drug resistance, on the other hand, develops while someone is on therapy. This can occur when someone receives an inadequate regimen and/or is nonadherent to their therapy.
9/ Next time we will discuss when and how to test for acquired drug resistance. For now, remember the #keyclinicalcorrelate that all patients should receive a baseline HIV genotype upon diagnosis to check for transmitted drug resistance.
10/ With the caveat that results of a baseline HIV genotype do not necessarily change what regimen we will start. Additionally, current guidelines do not recommend obtaining resistance testing to INSTIs. This makes sense given the low rates of INSTI TDR.
11/ But as INSTIs are used with increased frequency, this may change. For now though, only genotypic resistance to evaluate for NRTI, NNRTI, and PI resistance is recommended. clinicalinfo.hiv.gov/en/guidelines/…
12/ Stay tuned for our next episode when we will review the different types of #HIVDrugResistance tests and how they are done.
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Great conversation with @IAS_USA panelists on the new guidelines!
For those with tuberculous meningitis, high-dose steroids should be initiated along with tuberculosis treatment and ART should be initiated within 2 weeks after starting tuberculosis treatment and steroids
✅TAF and rifampin OK
✅Do DTG bid if using rifampin
✅DTG daily OK if using rifabutin
🚫BIC with rifamycins
💥Also new: earlier ART start in crypto meningitis recommended if access to LP & monitoring
"For individuals with cryptococcal meningitis with access to close monitoring and supportive care for adverse events, ART should be initiated 2-4 weeks after starting antifungal therapy"
2/
Curiosity is an itchy state of mind
Lying West of wonder and East of ecstacy
Not well localized in a brain bound by murmuring limbics
Not with its own bump in the phrenology of CT and PET
A defiantly defining feature of being human and alive
3/
Compassion is a practice, of the brain not defined by it
I aspire to compassion as I once yearned to be cool
Seems some people just are; for me empathy takes time
For me, curiosity is the hook, line and sinker
Caught my attention to compassion’s lifetime work.
When CrCl <30, technically should stop TAF and FTC/3TC. TAF can be used down to CrCl 15 not on dialysis (think HBV monoinfection tx data) BUT technically FTC or 3TC should be renally-dosed at these lower CrCl.
I've seen FTC and/or 3TC continued at these lower CrCl levels since risk of lactic acidosis and/or other AE is still low but technically would not be "appropriate"