HIV/TB, INSTI resistance

Mutations: M184V,T97A
Comorbidities: None
Comedications: Ethambutol, Pyrazinamide, Rifampin, Isoniazid
Treatment history: ATV/r (Atazanavir-ritonavir/Reyataz and Norvir) , RAL (Raltegravir/Isentress) , TDF/FTC (Truvada)
Current regimen: None
Adherence: No options selected
CD4: > 200
Viral load: Low (200 - 100,000)
HLA-B5701: Negative
Tropism: Unknown
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Submitted by maunank on Thu, 05/13/2021 - 09:18

40 year old patient with HIV, treatment experienced (prior history of TDF/FTC+RAL, TDF/FTC+RAL+ATVc), off ART for > 1 year, current genotype without resistance (but history of M184V and T97A), newly diagnosed with pulmonary TB.  Started on RHZE, with Rif optimized to 1200mg to achieve therapeutic drug levels.  

From MTB standpoint, the preference is to continue to use Rifampin, which limits the ART options. While we could use Rifabutin, there is just less actual evidence for effectiveness against MTB, and dose optimization and side-effects often ends up being challenging. 

Given the prior INSTI resistance, independent of RIF usage, strategy would include DTG 50mg BID in the context of background INSTI resistance. Given the RIF drug interaction with DTG, the question is whether to increase the dosing even further.  We considered strengthening the regimen further (e.g., addition of EFV, but would face the additional EFV-DTG interaction).  Options we had considered:

1.RHZE+ TDF/FTC+DTG 100mg BID (there is a little data that might be extrapolated to support this, but generally found paucity of PK data on DTG dosing strategies with RIF coadministration that would  achieve the equivalent of DTG 50 BID doses [without RIF] )

2.Switching to RBT/HZE, + TDF/FTC+ DRV/r +/- DTG 50mg BID

We talked about using TDF/FTC/EFV, as we often do with our patients on Rifampin, but didn't feel this was a very robust regimen in context of M184V and the RIF-EFV interaction that already lowers the EFV levels somewhat.

Given TB treatment is only temporary and T97A is really a RAL mutation/polymorphism, wondering if we might get away with option #1, and then eventually just transitioned to TAF/FTC+DTG 50mg BID once Rifampin and TB therapy are discontinued.

Regimen Weighted Score Active Drugs Total Pills Frequency (x/day)
DTG+TDF/FTC 2.5 2 3 2
DTG+TAF/FTC 2.95 2 3 2
DTG+IBA+TDF/FTC 6.55 3 3 2
DTG+IBA+TDF/FTC 6.75 3 3 2
RAL+EFV/TDF/FTC 6.9 3 5 2
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Submitted by PreethiMol on Tue, 11/16/2021 - 23:59

With CD4 > 200, defer ART treatment till intensive Tb treatment is completed.

Repeat TDM at maintenance TB treatment phase if high dose rifampicin is still required? If not, patient can be started on HAART at 8 weeks of TB treatment with the treatment of TenvirEm + DTG 50mg BID.

If high dose of rifampicin is required in maintenance phase to achieve required optimal levels:

1) switch to TenvirEM + EFV 800mg , or

2) switch rifampicin to rifabutin

The M184V mutation is selected by lamivudine (3TC) and emtricitabine (FTC) & it is often conferred as "good resistance" as it increases the susceptibility of certain NRTIs such as Tenofovir.

Studies have shown rifampicin & efv interaction causes a reduction of approximately 25% of efv.