Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

OBJECTIVE The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.METHODS: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8-9), or high (>9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up.RESULTS: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58).CONCLUSIONS: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions.

Impact of corneal cross-linking on topical drug penetration in humans.

PURPOSE To analyse the influence of corneal cross-linking (CXL) with ultraviolet-A (UV-A) and riboflavin on drug permeability in human subjects. METHODS Keratoconus patients (n = 23; mean age 26.9 ± 5.8 years) undergoing a standard CXL procedure with UV-A (5.4 J/cm(2) , 30 min) and riboflavin in one eye were included in the study. The pupillary diameter, measured before and every 3 min for 30 min after the topical application of one drop of 2% pilocarpine, was used as an indirect measure of the corneal permeability. The pupillary diameter was measured with an infrared pupillometer device before (baseline) and 4 months after CXL. RESULTS Prior to pilocarpine application, no significant difference in the pupillary diameter was detected before CXL and 4 months later. The mean decrease in the pupillary diameter after the application of pilocarpine was similar at baseline and the 4-month follow-up visit: mean decreases of 3.9 and 3.7 mm were observed 30 min after pilocarpine application, respectively (p > 0.05). CONCLUSIONS No significant influence of CXL on the corneal penetration of topically applied pilocarpine was observed in this clinical study.

Enamel Surface Changes After Exposure to Bleaching Gels Containing Carbamide Peroxide or Hydrogen Peroxide.

OBJECTIVE This study evaluated the differences in enamel color change, surface hardness, elastic modulus, and surface roughness between treatments with four bleaching gels containing carbamide peroxide (two at 10% and one each at 35%, and 45%) and two bleaching gels containing hydrogen peroxide (two at 40%). METHODS Enamel specimens were bleached and color changes were measured. Color change was calculated using either ΔE or the Bleaching Index (BI). Then, surface hardness, elastic modulus, and surface roughness of the enamel specimens were evaluated. All measurements were performed at baseline and directly after the first bleaching treatment for all carbamide peroxide- and hydrogen peroxide-containing bleaching gels. In addition, final measurements were made 24 hours after each of a total of 10 bleaching treatments for carbamide peroxide bleaching gels, and 1 week after each of a total of three bleaching treatments for hydrogen peroxide bleaching gels. RESULTS After the last bleaching treatment, respective ΔE scores were 17.6 and 8.2 for the two 10% carbamide peroxide gels, 12.9 and 5.6 for the 45% and 35% carbamide peroxide gels, and 9.6 and 13.9 for the two 40% hydrogen peroxide gels. The respective BI scores were -2.0 and -2.0 for the two 10% carbamide peroxide gels, -3.5 and -1.5 for the 45% and 35% carbamide peroxide gels, and -2.0 and -3.0 for the two 40% hydrogen peroxide gels. Each bleaching gel treatment resulted in significant whitening; however, no significant difference was found among the gels after the last bleaching. Whitening occurred within the first bleaching treatments and did not increase significantly during the remaining treatments. Surface hardness significantly decreased after the last bleaching treatment, when 10% carbamide peroxide was used. Furthermore, significant changes in the elastic modulus or surface roughness occurred only after treatment with 10% carbamide peroxide. CONCLUSION All six bleaching gels effectively bleached the enamel specimens independent of their concentration of peroxide. Gels with low peroxide concentration and longer contact time negatively affected the enamel surface.