HIV Epidemiology and Prevention Program, The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Curr Opin HIV AIDS. 2012 Nov;7(6):549-56. doi: 10.1097/COH.0b013e3283582c71.
HIV infection among MSM remains a significant issue. Data relevant to MSM populations from animal models, pharmacokinetic studies and clinical trials are summarized and challenges and potential consequences of use of preexposure prophylaxis (PrEP) by MSM are discussed.
Rectal simian-human immunodeficiency virus transmission in macaque models can be prevented by intermittent PrEP dosing. The Preexposure Prophylaxis Initiative (iPrEx) study found that daily oral emtricitabine-tenofovir disoproxyl fumarate (TDF/FTC) decreased HIV infection by 44% among 2499 high-risk MSM. Men with detectable levels of TDF or FTC in plasma and peripheral blood mononuclear cells experienced more than 90% protective effect, emphasizing the importance of adherence. In iPrEX and other studies, PrEP was generally safe and well tolerated. However, it appears that TDF use is associated with a small but significant decrease in mean bone mineral density. No risk compensation has been demonstrated, but this remains an area of potential concern when PrEP is used outside the setting of a placebo-controlled trial. Numerous PrEP trials in MSM are currently underway.
Oral FTC/TDF is effective in preventing HIV infection among MSM. Optimal PrEP agents and dosing regimens now need to be identified. Understanding the patterns of and impediments to PrEP use among MSM is vital and these should be monitored in ongoing demonstration projects and open-label studies.
男男性行为人群(MSM)中的 HIV 感染仍然是一个重大问题。本文总结了相关动物模型、药代动力学研究和临床试验数据,并讨论了 MSM 使用暴露前预防(PrEP)的挑战和潜在后果。
在恒河猴模型中,间歇性 PrEP 给药可预防直肠猴免疫缺陷病毒传播。暴露前预防倡议(iPrEx)研究发现,2499 名高危 MSM 每日口服恩曲他滨替诺福韦酯(TDF/FTC)可使 HIV 感染减少 44%。血浆和外周血单核细胞中可检测到 TDF 或 FTC 的男性,其保护作用超过 90%,强调了依从性的重要性。在 iPrEx 和其他研究中,PrEP 通常是安全且耐受良好的。然而,TDF 的使用似乎与平均骨矿物质密度的轻微但显著下降有关。虽然尚未证明存在风险补偿,但在安慰剂对照试验之外使用 PrEP 时,这仍然是一个潜在的关注领域。目前正在对 MSM 进行多项 PrEP 试验。
口服 FTC/TDF 可有效预防 MSM 中的 HIV 感染。现在需要确定最佳的 PrEP 药物和剂量方案。了解 MSM 中 PrEP 使用的模式和障碍至关重要,应在正在进行的示范项目和开放标签研究中监测这些情况。