Objective:Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons.Design and methods:The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft–Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy.Results:There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: −2.4 vs. −1.1 ml/min; P = 0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P = 0.02), and resolved after stopping pre-exposure prophylaxis (mean change: −0.1 vs. 0.0 ml/min; P = 0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy.Conclusions:In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.
Syphilis infection was associated with HIV incidence in an HIV-prevention trial that randomized participants to once-daily emtricitabine/tenofovir (FTC/TDF) vs placebo. FTC/TDF had no effect on the association between incident syphilis and HIV acquisition; syphilis infection did not decrease FTC/TDF efficacy.
Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.
Syphilis has existed for millenni, but its epidemiology was only recently linked to men who have sex with men (MSM) after the introduction of penicillin in the 1940s; the syphilis epidemic became concentrated within the MSM community in subsequent decades. The HIV/AIDS epidemic in the 1980s led to a surge of new syphilis cases and revealed the potentiation between HIV and syphilis, as evidenced by a shift in the natural history of neurosyphilis. In response, MSM revolutionised their sexual behaviour by implementing community-driven seroadaptive strategies to stem HIV transmission. The Centers for Disease Control in the US called for the elimination of syphilis in the late 1990s since the rates had fallen sharply but this effort was overtaken by a resurgence of global outbreaks among MSM in the 2000s, many of which were linked to methamphetamine use and sexual networking websites. Syphilis remains highly prevalent today, especially among MSM and individuals infected with HIV, and it continues to present a significant public health conundrum. Innovative syphilis prevention strategies are warranted. MSM engaging in high-risk behaviour such as condomless anal receptive intercourse, sex with multiple partners or recreational drug use should be routinely screened for syphilis infection; they should also be counselled about the limits of seroadaptive behaviours and HIV pre-exposure prophylaxis as they relate to syphilis transmission.
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