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ART When Pending Resistance Data
Weighing Boosted vs Unboosted Options for a Patient Who Requires Treatment Prior to Availability of Resistance Data

Released: June 21, 2017

Expiration: June 20, 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. Here, a young woman with newly diagnosed HIV infection and Pneumocystis pneumonia is anxious to start ART. The discussion that follows examines optimal timing for ART initiation as well as recommended regimens in this scenario.

Case Details
A 29-year-old woman recently presented to emergency care with fever, chills, nonproductive cough, and increasing dyspnea on exertion. A rapid HIV test was reactive, and a chest radiograph revealed diffuse interstitial infiltrates but no effusions, nodules, or adenopathy. Other laboratories were remarkable for normocytic anemia, a hemoglobin of 10 g/dL, and an arterial blood gas with pH 7.50, pCO2 22 mm Hg, and pO2 61 mm Hg.

The patient was initiated on trimethoprim/sulfamethoxazole plus prednisone with good clinical response. After 48 hours, her CD4+ cell count returned at 12 cells/mm3, and a bronchoalveolar lavage identified Pneumocystis jirovecii. On Day 5 of treatment, she had plasma HIV-1 RNA of 172,000 copies/mL and tested HLA-B*5701 positive with drug resistance genotype pending. She is eager to start ARVs immediately.

When to Start
Data from the 48-week ACTG 5164 study demonstrate the benefits of starting ARVs within 2 weeks of initiating therapy for acute opportunistic infections (OIs). Including those infected with Pneumocystis jirovecii, patients treated this early took longer to progress to a new AIDS-defining illness or death compared with those who deferred ART until after completion of OI therapy. Based on these data, for a willing patient such as in the case described above, it is strongly recommended that ART be initiated sooner than later.

What to Start
One unique feature of this case is the desire to initiate ART prior to the availability of drug resistance data, which warrants the use of drugs with high barriers to resistance for which transmitted resistance is relatively rare. For these reasons, NNRTI-based regimens should be avoided. Immediate goals include minimization of the emergence of any additional resistance before receipt of baseline resistance data and assessment of virologic response.

Traditionally, the first choice in this setting has been a regimen containing a pharmacologically-boosted PI, but more recent guidelines have expanded to include dolutegravir (DTG)-based regimens. Guidance from the DHHS recommends one of the following for this situation:

  • Darunavir (DRV)/ritonavir (RTV) + emtricitabine (FTC)/tenofovir alafenamide (TAF) or FTC/tenofovir disoproxil fumarate (TDF)
  • DTG + FTC/TAF or FTC/TDF

Resistance to DRV/RTV and DTG emerges slowly. Furthermore, transmitted resistance to DRV and DTG remains rare, with DTG demonstrating the highest barrier to resistance of available INSTIs. This would make regimens including elvitegravir (EVG) or raltegravir (RAL) less optimal for this patient. It is also notable in this case that the patient is HLA-B*5701 positive; as such, if DTG were chosen, it could not be given with abacavir (ABC)/lamivudine (3TC) as a single-tablet regimen but would need to be given with a tenofovir-based NRTI backbone as mentioned above.

Your Thoughts
Would you initiate ART immediately for this patient or wait? What regimen would you initiate for a patient who you would treat before resistance results are available? Please share your experiences and insights by joining the conversation in the comments box below.

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When selecting an initial ART regimen before resistance data are available, which of the following do you recommend?
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