LTBI + HIV

Mutations: None
Comorbidities: Tuberculosis
Comedications: Isoniazid, rifapentine
Treatment history: None
Current regimen: DRV/c/TAF/FTC (Symtuza)
Adherence: Penalize regimens with IV/IM dosing
CD4: ≤ 200
Viral load: Low (200 - 100,000)
HLA-B5701: Negative
Tropism: Unknown
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Submitted by nicky.mehtani on Sun, 03/22/2020 - 08:29

A patient with HIV (CD4 180, VL 90k, intermittent adherence to DRV/c/TAF/FTC), schizoaffective disorder and poor medication adherence was recently diagnosed with LTBI. Given the high risk of progressing to active TB, the provider is wanting to treat the LTBI as efficiently as possible and the patient agrees to a weekly DOT regimen with 3HP for LTBI treatment (which we would be able to provide). We would like to treat with 3HP and DTG (ideally QD given favorable PK data from DOLPHIN study vs. BID) + TDF/FTC. However, DTG-based regimens do not yet seem to be an option on HIV-ASSIST. 

Regimen Weighted Score Active Drugs Total Pills Frequency (x/day)
BIC/TAF/FTC 0.75 2 1 1
DTG+TAF/FTC 0.75 2 2 1
DTG+TDF/FTC 1.05 2 2 1
DRV/c/TAF/FTC [Current regimen] 1.25 2 1 1
DRV/c+TDF/FTC 1.35 2 2 1
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Comments

Submitted by maunank on Tue, 11/03/2020 - 09:29

Nicky, Great question/comment. First, I will note that the system is essentially 'assuming' the possibility of an M184V being presented in the context of treatment failure with the PI+2NRTI regimen they are currently on; it tries to take the most conservative approach. If you feel confident that the genotype (taken on meds) is reflective of the virus' underlying resistance pattern, you could consider entering the case without any 'current drugs'. We have been closely following the various studies related to the various rifamcyin interactions. In part, we are hesitant to make recommendations that might be discordant with the DHHS and other guidelines, even though there may be emerging evidence. There are a handful of areas where the guidelines may get updated in the future: (1)As of now, there was pharmacokinetic data that showed that when Rif is coadministered with TAF, the intracellular tenofovir-DP concentrations were still 4X higher than those achieved by TDF administration alone without a rifamycin https://pubmed.ncbi.nlm.nih.gov/30815689/. However, the DHHS Treatment guidelines still list this interaction (rifampin and TAF) as "Do not coadminister, unless benefits outweigh the risks". (2)Similarly, the DHHS OI guidelines from 2020 still list INH as 'remaining a preferred therapy' which is discordant from the udpated CDC/IDSA/ATS latent TB guidance. When discussing the 3HP regimen, they note the lack of interaction with once weekly rifapentine and efavirenz, and also note that RAL was largely unaffected. The guidance as of now still only suggests that 3HP is 'recommended when used in persons receiving efavirenz or RAL'. Similarly, the DHHS treatment guidelines still list BIC, DTG, and EVG/c as bold, "Do not coadminister" with Rifapentine. As you noted, Kelly Dooley et al. published the results of the DOLPHIN study earlier this year (https://pubmed.ncbi.nlm.nih.gov/32240629/). In this trial, 3HP increased DTG clearance by 36%, and all but one had trough values that were above the 90% MIC for DTG. This PK data would suggest that one could use once weekly INH and rifapentine without dose adjustment of DTG. However, it is also worth considering adherence and the clinical context. It should be noted, however, that in the DOLPHIN study, participants were enrolled that were already virologically suppressed, and the data suggested that almost everyone maintained suppression; one individual did have a detectable Vl at 24 weeks which suppressed again with adherence counseling. So from a PK standpoint, you might be able to get away with the drug interaction, but at the moment HIVASSIST is not making that recommendation until this is formally reviewed and recommended in the guidlelines. I would also consider being cautious in a patient who has ongoing viremia/treatment failure and poor adherenc. If they are poorly adherent to the ARV (but adherent to the 3HP), you might end up with DTG exposure that is suboptimal.