Patient with non compliance

Mutations: M184V, V90I, I93L, T97A, N155H, G163G, Y143C
Comorbidities: None
Comedications: None
Treatment history: DRV/r (Darunavir-ritonavir/Prezista and Norvir) , RAL (Raltegravir/Isentress) , MVC (Maraviroc/Selzentry) , ABC/3TC (Epzicom)
Current regimen: DRV/c/TAF/FTC (Symtuza)
Adherence: Penalize regimens with IV/IM dosing
CD4: Unknown
Viral load: Suppressed (<50) for less than 6 months or Low Level Viremia (<200)
HLA-B5701: Negative
Tropism: R5 virus
View results
Submitted by maunank on Wed, 06/03/2020 - 10:28

65 y.o. male c hx HIV (CD4 111, VL 1720 January 2020; and more recently Vl still ~3000), supposedly on Symtuza but with a long history of noncompliance, hepatitis C (genotype 1A,  s/p Harvoni  with SVR at 12 ), HTN, COPD, recent stroke, and multiple missed appointments. Has been on and off ARV for 20 years. Over the last ten years, has been on DRV/r+RAL with suppression, and then viremia; DRV/r, RAL, MVC (R5) with Vl mostly <400, TDF/FTC/EVG/c when INSTI genotype showed no mutations, subsequently developed  T97A/T,N155H/N,G163G/R,Y143C/Y; switched to ABC/3TC+DRV/r (unsure of reasons for epzicom), suppressed, and then had intermittent viremia to 30,000 with periods of suppression. Genotypes throughout this time largely only showing M184V and no significant PI resistance (  R83K, E122K, D123E, I178L,  L214F, R277K, T286A, I293V, E297K, S322T,           I329L, M184V,  V3I, T12E, L19I, S37N, I93L).  Nearly suppressed after this on TAF/FTC+DRV/r (thought prezcobix was too big).  Had a CVA subsequently. 

 

Mutation summary:

NNRTI: M184V, V90I/V

PI: I93L

INSTI: T97A/T, N155H/N, G163G/R, Y143C/Y, 


Regimen Weighted Score Active Drugs Total Pills Frequency (x/day)
DRV/c/TAF/FTC [Current regimen] 1 2 1 1
DRV/r+TAF/FTC 2.7 2 3 1
DTG+DRV/c/TAF/FTC 2.75 2.67 3 2
DTG+DRV/r+TAF/FTC 3.15 2.67 5 2
DRV/c+BIC/TAF/FTC 3.3 2.67 2 1
Ask on the National Clinical Consultation Center

Comments

Submitted by maunank on Wed, 06/03/2020 - 14:32

In short, I think I would probably be inclined to leave him on the Symtuza. Or consider adding DTG BID until suppression if he is willing and then simplifying to just symtuza to maintain suppression. I am surprised he doesn't have more demonstrated significant NRTI resistance given his long exposure, and view the TAF/FTC backbone cautiously here. With that said, he has not picked up significant DRV resistance and I think if adherent he will probably suppress with DRV/c/TAF/FTC. My thought process starts from the time of INSTI resistance/failure. Prior to that,he likely had older regimens and exposure that probably included NNRTI failure with M184V (for which switching to PI+2NRTI, or PI+INSTI or INSTI+2 NRTI could have been considered based on older studies of regimens post NNRTI failure even with compromised NRTIs). There is limited clinical trial data to guide selection of regimens after failing an INSTI based regimen, and this patient unsurprisingly has picked up INSTI mutations after failure of EVG and RAL, with retained DTG susceptibility (low level resistance). The guidelines currently suggest: Boosted PI + 2 NRTI, BID DTG+ 2 NRTI for which at least one is active, or BID DTG+Boosted PI as the options in the setting of RAL/EVG resistance with retained DTG susceptibility. In this setting I think DTG BID + 2 NRTI or DTG BID + DRV/c are likely less robust regimens in my mind than PI/b+2NRTI with this resistance pattern. Of course he also has had ongoing viremia in the face of PI+2NRTI (with an M184V). In ARTEMIS, people with virologic failure even at 192 weeks on DRV/r generally lacked development of major PI RAMs (and I think even relatively few NRTI resistance); I think your patient has a similar profile in that regard. There is an older analysis by Judy Currier and folks that looked at the approach post-PI failure in the initial ACTG PI first line RCT's. Similar to your patient, most did not have PI mutations, and htose w NRTI RAMs most commonly had M184V and relatively few had TAMs. Most people remained on their same regimens (2/3), and ~60% subsequently suppressed by 24 weeks. I think particularly with low level viremia, this option seems reasonable to me ( I think similar to what Dr. Enron suggested). There are similar-ish data out of EuroSida looking at a few thousand individuals with prior failure/experience, with a similar % suppressed I think. In POWER, I think ~75% of those with similar baseline DRV phenotypic scores to your patient had 48 week virologic response. While none of these outcomes are as good as in treatment naive patients, I think they suggest that your patient could do okay (and not sure there is a ton of evidence for better regimens). In terms of adding an NNRTI, there are 4 or 5 studies evaluating the combination of PI+NNRTI, mostly all in treatment experienced patients; the most recent I believe is PROBE. But these are all dual treatment studies, and several were in suppressed patients, so it is questionable how much one can extrapolate. If suppressed, DRV/r+RPV may be non-inferior to triple drug regimens in terms of virlogical response. Among older studies in Naive patietns (i.e. viremic) that looked at Kaletra+Sustiva; in one, they had nearly 800 participants and was randomized--the virologic efficacy was similar to using EFV+2NRTI, though those that failed did have more resistance. I don't think there are a lot of situations in which I would be jumping to DRV/r+(RPV or DOR), but I think the data suggest that it probably has biological efficacy. Overall, I would be cautious about adding a single fully active drug to a regimen that should work in an intermittently adherent patient. I I think if I were to think of an 'intensive'/'consolidation' approach , I would probably be considering adding BID DTG as a drug with higher barrier to resistance. There is some data on using BID DTG even after RAL/EVG failure. In the VIKING, I believe ~75% had viral suppression with BID DTG following RAL failure with higher rates of suppression as long as there was not a Q148 mutation. In SAILING, a study of treatment experienced but INSTI naive patients with 2 class resistance, DTG in combination with up to two other ARV was well tolerated and achieved undetectable viral loads in ~71% of indivdiuals (higher with lower baseline viral load). This makes me think that inclusion of DTG could offer you a more robust regimen, but BID dosing is likely to be challenging and intermittent adherence could compromise preservation of INSTIs as a drug class in the future.