Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

The polymorphism of progesterone: stabilization of a 'disappearing' polymorph by co-crystallization.

Progesterone has been known to be polymorphic for over 70 years, and crystallization conditions for the production of both experimentally characterized polymorphs have been repeatedly reported in the literature up to 1975. Nevertheless, our attempts to produce crystals of the metastable form 2 suitable for single crystal X-ray diffraction failed until the structurally related molecule pregnenolone was introduced as an additive into the crystallization solution. Accurate low temperature crystal structures were obtained for forms 1 and 2, pregnenolone and a newly discovered pregnenolone-progesterone co-crystal, which appeared concomitantly with progesterone forms 1 and 2. Computational work based on the experimental crystal structures and those generated by a search for low energy structures showed that the crystallization of enantiomerically pure progesterone results in a more strained conformation compared with the racemate due to the rotation of the acetyl and 21-methyl groups. The role of impurities or additives in influencing crystallization outcome is discussed.