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Multiple Comorbidities and Potential DDIs
Selecting ART for an Aging Patient With Multiple Comorbidities and Potential Drug–Drug Interactions

Released: May 31, 2017

Expiration: May 30, 2018

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In this HIV cases series, we highlight common patient case scenarios and the critical decision making that goes into selecting optimal patient management strategies. This case features a treatment-naive, HIV-infected man in his early 60s with cardiovascular, pulmonary, and renal comorbidities. Discussed below are key considerations for what may direct the selection of DHHS-recommended first-line ART in this older man.

Case Details
A 61-year-old man recently diagnosed with HIV infection presents to initiate ART, communicating that he would prefer a regimen with QD dosing. Baseline testing previously revealed a CD4+ cell count of 620 cells/mm3, HIV-1 RNA of 55,000 copies/mL, wild-type (sensitive) virus, and HLA-B*5701 negativity. Serum creatinine was 1.6 mg/dL (eGFR 49 mL/min), LDL cholesterol was 82 mg/dL, and HDL was 38 mg/dL.

On physical examination, his BMI was 30, and he was hypertensive despite receiving lisinopril and low-dose carvedilol. Notably, he experienced a myocardial infarction 3 years ago that is being medically managed with the beta-blocker, low-dose aspirin, and atorvastatin, and he has reactive airways disease, which is best controlled with the inhaled steroid fluticasone.

Considering Comorbidities
Although he is older than most men diagnosed with HIV infection in the US, this patient is typical of the aging American. He qualifies as obese, with multiple diagnoses potentially related to lifestyle choices. His history of a myocardial infarction and continued hypertension stand out, and although these will influence the selection of his ART, research tells us that treating his HIV infection can reduce his risk of heart disease and stroke. The landmark START trial found that early vs delayed ART protected those with CD4+ cell counts > 500 cells/mm3 from serious AIDS and non-AIDS–related events, including cardiovascular disease. Post hoc analyses then found that the benefits of earlier ART appeared to be even greater for those who were older than 50 years of age or demonstrated cardiovascular risk. Similarly, ample data suggest that moderate renal insufficiency, which this man has, generally improves with the treatment of HIV infection. Therefore, there is no question of whether to start ART, but of what to start.

Picking ART, Avoiding Pitfalls
At a heightened risk for diseases associated with aging, people living with HIV are particularly prone to polypharmacy, which adds the challenge of crafting a regimen that will not exacerbate one, or often several, comorbid conditions or engender dangerous drug–drug interactions.

DHHS-recommended first-line regimens currently include 9 unique ART combinations:

  • Dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC)
  • DTG + emtricitabine (FTC)/tenofovir alafenamide (TAF)
  • DTG + FTC/tenofovir disoproxil fumarate (TDF)
  • Elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF
  • EVG/COBI/FTC/TDF
  • Raltegravir (RAL) + FTC/TAF
  • RAL + FTC/TDF
  • Darunavir (DRV) + ritonavir (RTV) + FTC/TAF
  • DRV + RTV + FTC/TDF

Given the renal and bone advantages of TAF over TDF, the 4 TDF-containing regimens can be eliminated. In particular, for a patient with CrCl < 50 mL/min, FTC/TDF would require a dose adjustment or discontinuation, which would be suboptimal.

We can also dispense with the sole remaining protease inhibitor-based regimen: boosted DRV plus FTC/TAF. Relatively lipid unfriendly and with high drug–drug interaction potential, a boosted PI would be a poor choice for this patient, who needs to maintain low LDL cholesterol. In addition, his dependency on fluticasone makes any regimen containing RTV or COBI a nonstarter, as these interfere with corticosteroid metabolism, and coadministration has been associated with Cushing syndrome and even adrenal insufficiency. For this reason, the regimen of EVG/COBI/FTC/TAF would also be suboptimal.

This leaves us with 3 remaining recommended options, including DTG/ABC/3TC. Some clinicians would be hesitant to use this ABC-containing combination in a patient with cardiovascular disease, given that some studies have shown an association between ABC and cardiovascular disease risk. 3TC also requires a dose adjustment for a patient with CrCl < 50 mL/min. As such, the single-tablet DTG/ABC/3TC regimen might be suboptimal for the case patient.

Keeping the Patient Healthy and Happy
What is likely best for this patient is a regimen that contains FTC/TAF in combination with either DTG or RAL. Both regimens would be expected to be lipid neutral and not interact with any of his current, or likely future, medications. RAL requires BID dosing, which may be problematic for this man. DTG is given QD and has a higher barrier to drug resistance, which can be useful if adherence flags. Although the FTC/TAF plus DTG regimen comprises 2 pills rather than 1 fixed-dose combination, many patients appreciate that these pills are relatively small.

Certainly, the best ART for a patient can sometimes be found on DHHS list of alternative regimens. Of these, the only one that might be considered for this patient is rilpivirine (RPV)/FTC/TAF. This single-tablet regimen is well tolerated but does have a food requirement, as it needs gastric acid for the RPV to be absorbed; this makes coadministration with acid blockers problematic. Because of this limitation, I would advise this patient to start with FTC/TAF plus DTG.

Your Thoughts
As illustrated in the case above, selecting ART sometimes requires a tightrope walk in which the treatment of HIV is balanced against exacerbating comorbidities or causing dangerous drug interactions. What ART would you have recommended for this patient? What factors influence which regimen you would use?

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When selecting an initial ART regimen for an older man with moderate renal impairment, elevated cardiovascular disease risk, and ongoing corticosteroid use, which of the following is your preferred choice?
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