HIV: 36I and M41L, concern for possible M184V. Initially diagnosed with HIV in 1995,. Nadir CD4 count of 6 from 1996. Initiated on darunavir, raltegravir, and etravirine in 2/12 after he re-presented for care Well controlled on this regimen for a period of time. Genotype 10/2011 c no sig resistance. Of note he had repotedly a 36I mutation. Looking back at records, he was on "salvage regimen" when in florida.Records were not able to be obtained, concerns that perhaps he could have an M184V and/or TAMs and this is why this regimen was picked.
More recently, he has had significant difficulties with compliance. His regimen was altered to try to decrease pill burden. On most recent genotype he has M41L. n 3/2018 he said went through a period where he was not taking his medications well for last 2 mos or so but was now is "back on track". However his CD4 was still below 200 and VL was 144 when checked 3/2018. We had asked him to come back for G6PD testing and repeat CMP as creatinine was elevated and we wanted to start dapsone (concerns with electrolyte abns over starting bactrim), however he never did this. In 6/2018 he said he had been missing at least 2 days of ART a week due to forgetting or pain in his legs. At that visit VL was elevated and CD4 depressed. We checked Genotype and integrase genotype which showed no resistance. At last visit he said he had been taking his medications faithfully since then however he got confused and thought he was not supposed to take the ritonavir. At visit 9/2018, CD4 was still low but VL was UD. At last visit VL was again elevated at 232 though he said he had been taking. We had asked him to come back for repeat labs and genotype but he had not.
Summarized previous hx below:
NRTI: suspected M184V, TAMS but never actually detected. M41L
Dx with HIV in 1995 , Nadir CD4 6 (1996). Originally elsewhere, was on a "salvage regimen", perhaps had been on Norvir and Epivir -Records were not able to be obtained, Had been on epzicom, raltegravir, etravirine, DRV/r and was suppressed for some time on this.
10/2011: Genotype (vl betweel 101,662 and 28,834)
NOVEL MUTATIONS DETECTED:Reverse Transcriptase Gene: A98S, E122K, D123E, D123K, D123N,K166R, T200A, T200V, L214F, E248D, E248K, E248NProtease Gene: V3I, T12Q, I15V, L19I, M36I, S37N
Fell out of care for a while around 2011-2012. 2011 VL was 28,834,CD4 was 2011. Was completely off of ART. Genotype with no significant resistance (but likely WT). At that time concerns that perhaps he could have an M184V and/or TAMs, Reportedly had a 36I mutation. Was started on DRV/r, etravirine, raltegravir.
____________________2012 DRV/r (BID), etravirine, raltegravir__________
Quickly suppressed-remained suppressed until
2018: VL was 9290, Genotype WT--Problems with adherence, problems with taking pills.
Reverse Transcriptase Gene: Protease Gene: NOVEL MUTATIONS DETECTED: Reverse Transcriptase Gene: A98S, D123N, I142V, K166R, T200A, L214F, E248N Protease Gene: V3I, T12Q, I15V, L19I, M36I, S37N
____________________2018: started on DTG(once daily)/DRV/r/Rilpivirine->Juluca/DRV/r (twice daily DRV/r)____________
2018: VL UD again
2019: VL 36: Genotype: M41L, A98S, M36I
later/2019: VL 152--had had significant non-compliance particularly in setting of dysphagia-extreme difficulty with swallowing pills.
later/2019: VL <20, CD4 dipped down to 125, continued compliance issues
8/2019: VL 150 _________________transitioned to Biktarvy_________________
end 2019: VL UD, CD4 170
now: VL UD --Compliance much improved, CD4 189
|Regimen||Weighted Score||Active Drugs||Total Pills||Frequency (x/day)|
|BIC/TAF/FTC [Current regimen]||2.2||2||1||1|
In a person with intermittent adherence, I am nervous about both potential one pill once daily options in this patient--DTG/RPV, or BIC/TAF/FTC. DTG/RPV has not been well studied in the setting of a person with background history of treatment failure, and RPV requires high calorie meal and you could end up with functional DTG monotherapy. Alternatively, the presence of M184V and TAMS and incomplete genotype history concerns me for functional monotherapy with BIC/TAF/FTC. There is emerging data that BIC/TAF/FTC may be sufficient to maintain suppression even in the face of background NRTI resistance, but I would use this regimen with caution recognizing that in the setting of intermittent adherence it could be suboptimal. Within HIV-ASSIST, agree with the prioritization of 3 active drugs in such a patient with history of treatment failure, despite being currently suppressed (I think the current regimen should have been entered as BIC/TAF/FTC rather than just BIC, but do not think it would impact the system's outputs signfiicantly). The simplest change would be adding DOR (slightly bigger pill size) or RPV (smaller, but meal requirement) to the BIC/TAF/FTC. With that said, the combination of DTG+RPV is better studied (albeit not in this type of patient history) in simplification studies, so TAF/FTC/RPV+DTG could also be a consideration if food requirements can be met.