Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose.Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24.Results. Mean change in HIV-1 RNA at day 8 was −1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily.Conclusions. DTG 50 mg BID–based therapy was effective in this highly treatment-experienced population with INI-resistant virus.Clinical Trials Registration. (NCT01328041) and (112574).
Context
Incidentally discovered adrenal adenomas are common. Assessment for possible autonomous cortisol excess (ACS) is warranted for all adrenal adenomas given the association with increased cardiometabolic disease.
Objective
To evaluate the discriminatory capacity of three-dimensional volumetry on computed tomography (CT) to identify ACS.
Design, Setting, Patients
Two radiologists, blinded to hormonal levels, prospectively analyzed CT images on 149 adult patients with unilateral, incidentally-discovered, adrenal adenomas.
Main Outcome Measures
Diameter and volumetry of the adenoma, volumetry of the contralateral adrenal gland, and the adenoma volume-to-contralateral gland volume (AV/CV) ratio were measured. ACS was defined as cortisol≥1.8 mcg/dL after 1mg dexamethasone suppression test (DST) and a morning ACTH ≤15 pg/mL.
Results
We observed that ACS was diagnosed in 35 (23.4%) patients. Cortisol post-DST was positively correlated with adenoma diameter and volume, and inversely correlated with contralateral adrenal gland volume. Cortisol post-DST was positively correlated with the AV/CV ratio (r=0.46, p<0.001) and ACTH was inversely correlated (r=-0.28, p<0.001). The AV/CV ratio displayed the highest Odds Ratio (1.40 CI 95% 1.18-1.65) and area under curve (0.91 CI 95% 0.86-0.96) for predicting ACS. An AV/CV ratio ≥1 (48% of the cohort) had a sensitivity of 97% and a specificity of 70% to identify ACS.
Conclusions
CT volumetry of adrenal adenomas and contralateral adrenal glands has a high discriminatory capacity to identify ACS. The combination of this simple and low-cost radiological phenotyping can supplement biochemical testing to substantially improve the identification of ACS.
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