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Patient With Comorbidities
Weighing Boosted vs Unboosted Options for a Patient With Comorbidities Who Desires an STR

Released: June 21, 2017

Expiration: June 20, 2018

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In this HIV case series, we highlight common patient case scenarios and the critical decision making that goes into selecting optimal patient management strategies. In the case below, ART considerations for a middle-aged man with multiple comorbidities who is open to starting ART with a single-tablet regimen 2 years after his HIV diagnosis are discussed.

Case Details
A 50-year-old man was diagnosed with HIV in 2015 and had a CD4+ cell count of 450 cells/mm3. He was reluctant to start ART at that time. He has diabetes mellitus, hypertension, and chronic kidney disease (CKD). He is currently receiving insulin and lisinopril for his chronic medical problems. His CD4+ cell count has declined to 175 cells/µL, and his plasma HIV-1 RNA levels have peaked at 200,000 copies/mL. His baseline drug resistance genotype shows wild-type virus, and he is HLA-B*5701 negative.

The patient currently has a creatinine level of 2.4 mg/dL and an estimated glomerular filtration rate (eGFR) of 40 mL/min; urinalysis showed 3+ protein. He is now ready to start ART and strongly desires a single-tablet regimen.

Choosing a Single-Tablet Regimen
Considering the patient’s desire for a single-tablet regimen, the table below lists both boosted and unboosted regimens as first-line recommendations of several organizations, with single-tablet regimens bolded.

Table. Recommended and Alternative First-line ART Regimens
 

Of the available guideline-preferred single-tablet options, I would consider both unboosted and boosted options, specifically, DTG/ABC/3TC or EVG/COBI/FTC with TDF or TAF. I would not consider a RPV-based single-tablet regimen for the case patient, as RPV is not recommended for patients with HIV-1 RNA ≥ 100,000 copies/mL or CD4+ cell count ≤ 200 cells/mm3.

Looking more closely at our potential options, TDF could be eliminated, as this agent is not recommended for patients with eGFR < 60 mL/min (or < 70 mL/min with COBI-based regimens). DTG/ABC/3TC would also be a suboptimal regimen for this patient, as 3TC requires dose modification and is not recommended to be given as a fixed-dose combination when a patient has an eGFR < 50 mL/min, as our case patient does. In addition, some clinicians would consider avoiding ABC, given that some studies have shown potential association between ABC use and cardiovascular disease risk in patients with cardiovascular risk factors, like our case patient. Of note, these findings are debated, as other studies have found no association.

EVG/COBI/FTC/TAF is a possibility for this patient, as it can be used in those with an eGFR ≥ 30 mL/min. It should be noted, however, that data with TAF are limited in patients with advanced renal disease. Current recommendations are primarily based on pharmacokinetic data and the results of GS-112, a single-arm EVG/COBI/FTC/TAF switch study conducted in patients with an eGFR of 30-69 mL/min. In this study, TAF was dosed at 10 mg/day. Although this study reported stable renal function after switching, only 33% of the patients had a baseline eGFR < 50 mL/min; furthermore, there was no control group. One disadvantage of this regimen is that it contains a pharmacologic booster, COBI, which is associated with several drug–drug interactions. For a patient with multiple comorbidities who may be receiving concomitant medications now or in the future, this should be a consideration in selecting therapy.

Considering Multitablet Regimens
Although this patient strongly desires a single-tablet regimen, given the challenges with the available single-tablet regimens, including contraindications with renal disease and potential for drug–drug interactions, I would suggest reviewing the advantages of multitablet regimens with this patient. In evaluating the non–single-tablet options, a regimen of DTG, RAL, or a boosted PI with FTC/TAF might be considered.

If you were to consider FTC/TAF with DTG, RAL, or a boosted PI, one concern would be that TAF is only available in a fixed-dose combination with FTC at a dose of 25 mg/day. This would result in patients receiving a higher dose of TAF than those in the GS-112 study. Of note, a boosted PI may also be a challenge for this patient due to current or potential future drug–drug interactions.

Alternatively, you could consider treatment options excluding tenofovir or ABC, such as a boosted PI or DTG plus 3TC. However, there are limited data with these regimens.

Your Thoughts
How would you select ART for this patient? Would you recommend a single-tablet or multitablet regimen? Please share your experiences and insights by joining the conversation in the comments box below.

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