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Dual Therapy
How New Data From IAS 2017 May Inform Dual-Therapy Options for HIV Treatment

Released: September 12, 2017

Expiration: September 11, 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. This case features a treatment-naive older man with elevated cardiovascular disease (CVD) risk and renal impairment and examines how data recently presented at 2017 International AIDS Society (IAS) meeting might inform his treatment options.

Case Details
A 55-year-old man who was recently diagnosed with HIV is eager to begin ART. His HIV-1 RNA is 210,000 copies/mL and his CD4+ cell count is 340 cells/mm3. He presents with significant CVD risk (10-year atherosclerotic CVD risk of 25%), diabetes, and renal impairment (CrCl 28 mL/min).

HIV Treatment: Are 2 Drugs Sufficient?
For decades, triple-drug therapy has been the standard of care for treatment of HIV infection. Recent data with 2-drug regimens have suggested that 3 drugs may not be necessary for all patients and may be an option for individuals for whom comorbid conditions are a concern. Prior to the 2017 IAS meeting, key studies examining dual therapy for initial ART included the following:

  • NEAT001/ANRS143 (N = 805): ritonavir (RTV)-boosted darunavir (DRV) plus raltegravir was noninferior to DRV/RTV plus emtricitabine/tenofovir disoproxil fumarate (TDF); however, diminished efficacy was observed with dual therapy in patients with high HIV-1 RNA/low CD4+ cell counts
  • GARDEL (N = 426): RTV-boosted lopinavir (LPV) plus lamivudine (3TC) was noninferior to LPV/RTV plus 2 NRTIs
  • PADDLE (N = 20): HIV-1 RNA < 50 copies/mL was observed in 90% of patients receiving dolutegravir (DTG) plus 3TC; 1 patient with HIV-1 RNA > 100,000 copies/mL experienced virologic failure (although later became resuppressed without ART change)

New Data From IAS 2017 on First-line Dual Therapy
At IAS 2017, exciting new data from 2 additional studies showed that first-line dual therapy can be highly effective regardless of baseline HIV-1 RNA.

The first was ANDES, an open-label phase IV study that randomized 145 treatment-naive patients to DRV/RTV plus either 3TC or 3TC/TDF. Note that a generic formulation of 3TC/TDF not available in all countries was used in this study. Overall, 95% and 97% of patients, respectively, achieved virologic suppression at Week 24. This treatment success occurred regardless baseline HIV-1 RNA, even with one quarter of patients having HIV-1 RNA > 100,000 copies/mL at entry. No cases of virologic failure occurred in the dual therapy arm, compared with 1 occurrence in the triple-therapy arm. Thus, first-line DRV/RTV plus 3TC seems quite promising, although it does rely on the use of a boosted PI.

The single-arm phase II ACTG A5353 study treated 120 ART-naive patients with DTG plus 3TC and expanded the eligibility criteria from PADDLE, allowing participants with baseline HIV-1 RNA up to 500,000 copies/mL to enter. As such, 31% of patients had HIV-1 RNA > 100,000 copies/mL at baseline. At Week 24, 90% of patients had achieved HIV-1 RNA < 50 copies/mL. Virologic suppression was comparable for patients in the high and low baseline HIV-1 RNA strata. Three patients experienced protocol-defined virologic failure; all 3 had documented DTG levels reflective of suboptimal adherence and 1 had treatment-emergent M184V and R263R/K mixture resistance mutations. Thus, inadequate dosing, not primary regimen failure, likely led to the emergence of drug resistance and/or viremia.

The Future of Dual Therapy
Based on preliminary findings, DRV/RTV or DTG plus 3TC appear to be efficacious first-line dual-therapy regimens in patients with any baseline HIV-1 RNA and may be appropriate options for patients where tenofovir- and abacavir-sparing regimens are desired. In the current case, it might be desirable to avoid abacavir because of the patient’s increased CVD risk. Avoiding tenofovir (even in the TAF formulation) might also be desirable given the patient’s CrCl of only 28 mL/min (TAF-containing regimens are approved for use in patients with CrCl of 30 mL/min or greater). It should be noted that neither the DRV/RTV or DTG plus 3TC regimen has yet been recommended as a preferred option in treatment guidelines, and, in the case of DTG plus 3TC, results from the fully powered phase III GEMINI-1 and -2 studies are awaited. Of note, numerous studies have examined the potential of dual therapy in the maintenance therapy setting, with the recent SWORD studies showing high continued efficacy with a switch from suppressive triple-therapy ART to DTG plus rilpivirine.

Your Thoughts
Do you think that dual-therapy ART is a viable treatment for some patients? Have you prescribed 2-drug regimens for any of your patients? Please share your experiences and insights by joining the conversation in the comments box below.

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Based on data from the ANDES and ACTG A5353 studies, how likely would you be to recommend dual-therapy ART in the first-line setting for specific patients?
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