HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population.

Dolutegravir and doravirine are individually safe and effective antiretroviral therapy (ART) components, but their combined use has not been studied in clinical trials and is not recommended in HIV treatment guidelines. We noted persons with HIV (PWH) receiving dolutegravir with doravirine at our Washington, DC, infectious disease clinic and undertook a service evaluation to understand why providers selected this ART, whether HIV virologic suppression was achieved and identify adverse effects of concomitant use. Case registry and prescriptions data identified 21 PWH receiving concomitant dolutegravir and doravirine with mean follow-up 576.1 days (range 413-751); frequent reasons for switching were multiple ART resistance (57.1%), proton pump inhibitor usage (28.6%) and renal failure (28.6%), with 52.4% switched from protease inhibitor or cobicistat-boosted regimens. Dolutegravir with doravirine alone was prescribed for 60%, and additional ART in 40%. During 12 months follow-up mean CD4 was 585.9 (baseline 570.7) with undetectable viral load in 77.8% (baseline 66.7%). No discontinuations for drug-related adverse events or virologic failure occurred. Dolutegravir with doravirine was well tolerated in small numbers of highly treatment experienced PWH at our clinic, achieving virologic suppression in most. Establishing the efficacy and safety of dolutegravir with doravirine for HIV treatment in randomized trials remains important.

Learned Value Shapes Responses to Objects in Frontal and Ventral Stream Networks in Macaque Monkeys.

We have an incomplete picture of how the brain links object representations to reward value, and how this information is stored and later retrieved. The orbitofrontal cortex (OFC), medial frontal cortex (MFC), and ventrolateral prefrontal cortex (VLPFC), together with the amygdala, are thought to play key roles in these processes. There is an apparent discrepancy, however, regarding frontal areas thought to encode value in macaque monkeys versus humans. To address this issue, we used fMRI in macaque monkeys to localize brain areas encoding recently learned image values. Each week, monkeys learned to associate images of novel objects with a high or low probability of water reward. Areas responding to the value of recently learned reward-predictive images included MFC area 10 m/32, VLPFC area 12, and inferior temporal visual cortex (IT). The amygdala and OFC, each thought to be involved in value encoding, showed little such effect. Instead, these 2 areas primarily responded to visual stimulation and reward receipt, respectively. Strong image value encoding in monkey MFC compared with OFC is surprising, but agrees with results from human imaging studies. Our findings demonstrate the importance of VLPFC, MFC, and IT in representing the values of recently learned visual images.