BACKGROUNDThe incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda. METHODSIn this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion. RESULTSA total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P = 0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P = 0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified. CONCLUSIONSAmong women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226.)

Resection of phaeochromocytoma and paraganglioma (PPGL) is traditionally preceded by alpha-blockade to prevent complications of haemodynamic instability intraoperatively. While there is general agreement on preoperative alpha-blockade for classic PPGLs presenting with hypertension, it is less clear whether alpha-blockade is necessary in predominantly dopamine-secreting tumours, normotensive PPGLs, as well as tumours that appear to be biochemically 'silent'. Preoperative management of these 'atypical' PPGLs is challenging and the treatment approach must be individualized, carefully weighing the risk of intraoperative hypertension against the possibility of orthostatic and prolonged postoperative hypotension. Consideration of antihypertensive medication pharmacology in the light of catecholamine physiology and PPGL secretory profile will facilitate the formulation of individualized preoperative preparatory strategies.

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The cytotoxic, antiplasmodial, and antitrypanosomal activities of two medicinal plants traditionally used in Cameroon were evaluated. Wood of Roxb. ex Hornem. aerial roots (Moraceae) and Spring (Selaginellaceae) leaves were collected from two different sites in Cameroon. cell-growth inhibition activities were assessed on methanol extract of plant materials against strain 3D7 and , as well as against HeLa human cervical carcinoma cells. Criteria for activity were an IC value < 10 μg/mL. The extract of did not significantly reduce the viability of at a concentration of 25 μg/mL but dramatically affected the trypanosome growth with an IC of 2.4 μg/mL. In contrast, at the same concentration, the extract of exhibited plasmodiacidal activity (IC value of 9.5 μg/mL) and trypanocidal (IC value of 0.9 μg/mL) activity. Both extracts presented low cytotoxic effects on HeLa cancer cell line. These results indicate that the selected medicinal plants could be further investigated for identifying compounds that may be responsible for the observed activities and that may represent new leads in parasitical drug discovery.