HBV/HCV/HIV M184V. Dolutegravir allergy

Mutations: m184v
Comorbidities: Chronic Renal (Kidney) Disease GFR 30-60
Comedications: Trimethoprim-Sulfamethoxazole, Azithromycin
Treatment history: 3TC (Lamivudine/Epivir)
Current regimen: FTC (Emtricitabine/Emtriva) , TAF (Tenofovir/Vemlidy) , DRV/c (Darunavir-cobicistat/Prezcobix)
Adherence: Patients who prefer once daily dosing, Patients with intermittent adherence, Increase prioritization of at least 3 active drugs, Penalize regimens with IV/IM dosing
CD4: ≤ 200
Viral load: Suppressed (<50) for more than 6 months
HLA-B5701: Negative
Tropism: Dual Tropic virus
View results
Submitted by MatthewHamill on Sun, 02/07/2021 - 16:39

59yr old AA man. HIV since at least 2004. 

- On Dar/c and Descovy consistently for 13 months.

New onset of renal dysfunction - creat 2.1; eGFR 39 (Jan 2021). 

Previous creats 1.1 - 1.4; eGFR >63. May 2020 Creat 1.4, eGFR 63 (had fluctuated between 1.2 and 1.4) . 

Chronic HBV (now treated but DNA pending).

- ALT 70s

Untreated HCV GT1b.

Long history of SUD/non adherence

HTN (was on HCTZ - stopped now).

Recently engaged, VL now <20, CD4 125 (previously) ranged 13-70

Distant ART history not known - presumably 3TC/TDF and NNRTI? not know what if any NNRTI mutations. 

Admitted to hospital with marked facial swelling when started Dolutegravir. Allergy team thought was likely Dolutegravir-related. 

UA was not done on last labs. 

I am reluctant to stop TAF given HBV and concerns for flare. 

Likely NNRTI experienced - and concern resistance, and for liver given untreated HCV and partially treated HBV

Integrase - facial swelling warranting IP stay secondary to Dolutegravir, concern for class effect

Mixed dual trophic virus

He would not be able to commit to ibalizumab

I don't think would qualify for fostemzavir with only M184V documented and VL<20 

i could switch to Entecavir for HBV but his HIV won't be adequately treated. 

Pending repeat labs in 1-2 days will keep on Prezcobix and Descovy pending these results.

 

Thoughts:

1. Continue current ART and very close FU of kidney function

2. Consider trial of  Doravarine + Dar/c + continue 3TC (for HBV and some HIV effect)

- Depending on NNRTI experience and previous resistance Dor might be active

3. Other NRTI

- he is a little anemic so want to avoid AZT, also don't think a BID regimen would succeed. 

- ABC will be partially active (but no HLA result)

4. Try to obtain fostemavir but BID and concern with HBV with Dar/c. I think he will not qualify even if he could take BID.

 

i am getting repeat labs and urine, renal USS and renal opinion. 

Any advice would be gratefully received. 

 

Thanks

 

Regimen Weighted Score Active Drugs Total Pills Frequency (x/day)
DTG+DRV/c/TAF/FTC 1.01 3 2 1
DTG+DRV/r+TAF/FTC 1.51 3 4 1
DRV/c+BIC/TAF/FTC 1.71 3 2 1
DRV/c/TAF/FTC [Current regimen] [Your preferred regimen] 1.76 2 1 1
DRV/c+DTG/RPV 1.77 3 2 1
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Comments

Submitted by nicky.mehtani on Wed, 02/17/2021 - 14:00

Below is a synthesis of a discussion involving a small number of consultants with the national HIV Warmline/National Clinician Consultation Center (UCSF): 

Thanks for the follow-up and sharing these details of the case. Given the limited history, we will assume that those 2018 and 2019 genotypes resulting as WT were off of ART (but please let us know if you think otherwise). 

In any case, definitely a tough case with the INSTI allergy issues. We were considering the below options as possibilities, but none are perfect. (They are also similar to what you had been originally thinking based on the initial post). 

Additional thoughts we had were that it would be helpful in this case to get an archived genotype. Even if we can't trust the archive to provide a full genotype history, if it did show a N103 + L100I, it would be helpful to know. 

Potential ART options and thoughts: 

  1. Switch to DRV/c + DOR + FTC (+ entecavir for HBV)  
    1. A lot of pills, but seems like the safest option given the scenario. 
    2. If very worried about the NNRTI history and you're able to get an HLA-B5701 and it's negative, could also switch the FTC to ABC/3TC to have closer to 3 active drugs. 
  2. Continue current regimen of DRV/c + TAF/FTC (vs. switch to Symtuza) and repeat Cr to assess whether it was an AKI or progression of CKD. However, if his eGFR is continuing to worsen on TAF exposure, will likely not be able to do this indefinitely. 
  3. Consider re-challenge of a non-DTG INSTI-based regimen under the supervision of Allergy & Immunology (or during hospitalization). Though, understand that the patient's circumstances may prevent this from being an option at the moment. 

Thanks so much for sharing!

Respectfully,

The NCCC HIV Warmline team