Abstract
Multidrug-resistant (MDR) HIV can be complicated to manage. Patients are often on a high pill burden regimen, taking antiretrovirals twice daily, and often have other comorbidities. This study is a case report of a patient living with MDR HIV, and considerations are taken into account when simplifying the patient from a ten-pill regimen to a unique and unconventional six-pill regimen. The patient was living with HIV/AIDS with an MDR virus on a five-tablet, twice-daily (ten total pill burden) regimen who was simplified to a unique and novel regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide + darunavir 600 mg twice daily + cobicistat + maraviroc twice daily. This unique regimen, which decreased the patient’s HIV pill burden from ten to six, has maintained virologic suppression 1 year after his antiretroviral therapy transition. When consolidating therapy in patients with MDR HIV, one regimen will not fit each individual patient. Our case demonstrates unique and unconventional dosing of darunavir 600 mg along with cobicistat as twice-daily pharmacokinetic enhancing which assisted in consolidating our patient’s regimen by a 40% decrease in pill burden. This change most importantly maintained virologic suppression and provides evidence for a potential option for similar patients with MDR HIV.
Keywords
With written approval from our patient, we present the case of a patient living with multidrug-resistant (MDR) HIV and the considerations taken into account when simplifying him from a ten-pill regimen to a unique, novel six-pill regimen, using cobicistat twice daily with darunavir.
Our patient is a 58-year-old black man living with HIV/AIDS for over 30 years on a deep-salvage, high pill-burden regimen secondary to MDR HIV. We assumed his care in September 2016. Per the previous clinic’s charts, the patient had been prescribed ten regimens, starting with zidovudine monotherapy in April 1995, leading up to most recently darunavir (DRV) + ritonavir (RTV) + maraviroc (MVC) + etravirine (ETR) + raltegravir (RAL), all taken by mouth twice daily, equaling a pill burden of ten tablets daily. The patient had acquired multiple resistance-associated mutations (RAMs) conferring high level resistance to protease inhibitors, nucleoside reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors. The patient’s RAMs, concomitant medications, and medical history are summarised in Table 1.
Patient data.
After assessing the patient’s RAMs, his most recent regimen of twice-daily RTV-boosted-DRV + ETR + MVC + RAL included a theoretical combined three fully-active agents; fully-active MVC and RAL with intermediate resistance to DRV and ETR. Due to the patient also taking metformin 1000 mg total daily dose, our clinic wished to avoid the potential drug–drug interaction with dolutegravir, in case he needed a dose increase of metformin. Our clinic is confident using elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) + DRV 800 mg once daily for patients with some resistance, most often M184V, which our patient had. 1 However, given the patient’s DRV mutations I54I/L/V and I84I/V, he requires twice daily dosing to count as partially active. This prompted the idea to using EVG/COBI/FTC/TAF + DRV 600 mg along with a second ‘booster’ dose of DRV 600 mg + COBI 150 mg. For the second dose, we chose COBI instead of RTV to keep the pharmacokinetic enhancer the same.
As the patient’s virus was fully suppressed, there was no reason to believe integrase resistance was present, therefore exchanging RAL for EVG kept one fully active antiretroviral (ARV). Furthermore, the patient’s virus conferred ‘low-level resistance’ to tenofovir; however, the presence of the M184V typically makes the virus hypersusceptible to tenofovir, so we counted this as another partially-active ARV.1–3 Additionally, although FTC resistance is present, given the M184V, it was also re-incorporated into his regimen to elicit the M184V mutation, as this decreases viral fitness.2,4 Finally, keeping MVC allowed for another fully-active ARV, now totaling two fully-active ARVs, two partial, and also re-introducing an ARV that should reduce viral fitness. These changes have decreased our patient’s daily pill-burden to six tablets daily, taking EVG/COBI/FTC/TAF + DRV + MVC in the morning and DRV + COBI + MVC in the evening.
In February 2018, the patient was transitioned to EVG/COBI/FTC/TAF + DRV + COBI + MVC, and a lab draw about 5.5 weeks later in March 2018 revealed a likely blip of 32 copies/mL while maintaining adequate immunologic function. His most recent lab prior to the regimen transition, December 2017, was also likely a blip of 35 copies/mL; both values considered to be virologically suppressed based on the CDC definition of HIV RNA <200 copies/mL.5,6 Furthermore, repeat labs in October 2018 (almost 35 weeks after the regimen switch), revealed that the patient’s virus has maintained complete virologic suppression with stable immunologic function, no significant changes in renal or hepatic function, and also an identical hemoglobin A1c percentage compared to ten months prior. Repeat labs in February 2019 revealed continued virologic suppression with stable immunologic function approximately 1 year after regimen switch.
When simplifying the patient to non-traditional combinations, pharmacokinetic and pharmacodynamic parameters of individual agents must be taken into consideration. Pharmacokinetic enhancers, COBI and RTV, are used in combination with most PIs and the INSTI, EVG. Currently, COBI is approved for once daily administration with DRV 800 mg daily, but is not recommended for use with DRV 600 mg twice daily, per FDA package labeling. 7 In a pharmacokinetic study, evaluating the use of twice daily COBI 150 mg and twice daily DRV 600 mg co-administered with once daily EVG 150 mg, pharmacokinetic parameters were similar for both EVG and DRV and the boosting ability of COBI was not affected. 8 In a human dose-ranging study comparing COBI to RTV, COBI 150 mg + EVG 150 mg was found to provide comparable boosting activity of EVG when compared to RTV 100 mg + EVG 150 mg. 9 In addition, RTV has potential to alter EVG levels: possibly increasing them due to CYP3A inhibition, as well as possibly decreasing EVG levels due to induction of UGT1A1, of which EVG is a substrate of both.5,10
Our patient remained virologically suppressed and reported adherence to and satisfaction with a regimen of EVG/COBI/FTC/TAF in the morning + MVC 150 mg twice daily + DRV 600 mg twice daily + COBI in the evening. Here is real-world use of cobicistat twice daily, which may provide a unique approach to simplifying ART in patients living with MDR HIV.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.