HIV暴露前預防投藥對台灣男男間性行為傳染愛滋疫情基礎再生數的影響：機率傳播模式研究

Abstract

背景：消除HIV疫情其中一項重要挑戰為急性期的傳播，急性期因空窗期的影響，沒辦法檢驗出感染HIV，故Test-and-Treat在此階段沒辦法發揮控制疫情的效果。是否PrEP的擴大實施能夠填補這塊空缺而成功控制消除HIV，目前仍不清楚。再者，若PrEP能夠幫助消除HIV疫情，是否會因現實中風險補償(導致不安全性行為增加)、不規則服藥及抗藥性病毒株浮現等實務問題而受影響，此問題仍需要更進一步的探討。 方法：透過建立一個真實機率傳播模式（Realistic stochastic model），模擬一個HIV陽性的高風險MSM（以下稱「指標個案」），在他的生命歷程中，有多少原本是HIV陰性的MSM會被他傳染。模擬以「天」為單位。指標個案皆從20歲感染HIV開始模擬起。模型參數皆使用目前最佳估計，包含HIV疾病進程、傳播機率、HIV Cascade、死亡率、ART以及PrEP效果等等。模擬終止條件為指標個案中途因非AIDS相關死亡、因AIDS死亡或達45歲。每個情境模擬1,000次，會得到1,000個R0值，取平均得到該情境R0的平均值。透過不同情境R0的模擬，評估Test-and-Treat, PrEP或兩者合併實施在公共衛生上的效果；另外，也會對平均每年性伴侶人數、風險補償（Risk compensation）、服藥遵從性、抗藥性以及針對高風險族群介入做敏感度分析，評估這些因素對公共衛生帶來的影響。 結果：HIV急性期造成的傳播，在伴侶≥50/year時，將使Test-and-Treat無法消除HIV疫情。然而，PrEP可以補足Test-and-Treat的不足，產生加乘作用。台灣MSM平均每年性伴侶人數為65人，實施Annual HIV testing followed by immediate ART合併50%的PrEP覆蓋率，並且服藥遵從性至少達到75%，才能夠消除HIV疫情。風險補償與抗藥性不會影響PrEP消除HIV疫情的效果。若只針對MSM高風險族群給予PrEP，實施Annual HIV testing followed by immediate ART合併針對高風險族群PrEP覆蓋率則須提高到75%，並且服藥遵從性至少達到75%，才能夠消除HIV疫情。同樣地，風險補償與抗藥性也不會影響針對高風險族群給予PrEP消除HIV疫情的效果。 結論：PrEP的擴大實施是必要的，才能夠填補Test-and-Treat的不足，達到消除HIV疫情的目標。此研究結果可以作為台灣目前被熱烈討論的議題是否公費補助PrEP以及如何補助提供參考與建議。

Background: An important barrier to eliminate HIV epidemic by 2030 is HIV transmissions occur in acute stage of HIV infection, the window period when the principle of HIV test-and-treat/treatment-as-prevention is not applicable. It remains unclear whether pre-exposure prophylaxis (PrEP), a highly effective approach to reduce HIV risk for HIV-negative men who have sex with men (MSM), can overcome this barrier which might jeopardize the global HIV elimination strategy. Methods: We constructed a realistic stochastic model that simulated the life course of an MSM with high-risk behaviors. The HIV infection started on 20-years-old. The model incorporated the best estimates for HIV disease progression, Transmission probability, death rate, antiretroviral therapy, PrEP, as well as HIV cascades (based on actual data in Taiwan). The basic reproductive number (R0) under each scenario was estimated by the average number of secondary HIV infections during 20-45 years, over 1,000 simulations. Evaluate the effects of Test-and-Treat strategy, scaling-up PrEP or combination of two strategies on public health. Moreover, sensitivity analysis was conducted, including contact rate, risk compensation, PrEP compliance, drug resistance. Results: HIV transmissions from acute stage accounted for more than two-third of secondary infections, under currently best estimate for relative infectiousness of acute stage (26-fold), when the index case has 50 sexual partners per year. Test-and-treat strategy alone would fail to reduce R0 to below 1 under such scenario. However, PrEP can supplement test-and-treat and make elimination feasible again. MSM in Taiwan has an average annual number of sexual partners of 65, the implementation of annual HIV testing followed by immediate ART combined with 50% PrEP coverage, and PrEP compliance of at least 75%, can eliminate the HIV epidemic. Risk compensation and drug resistance do not affect the effectiveness of PrEP in eliminating HIV epidemic. If target PrEP on high-risk group, the HIV epidemic can be eliminated by implementing annual HIV testing followed by immediate ART combined with 75% PrEP coverage on the high-risk group MSM and at least 75% compliance. Conclusion: HIV transmission during acute HIV infection cannot be prevented by HIV test-and-treat alone in certain high-risk scenario. It would be necessary to scale-up PrEP to make elimination feasible again. Our findings could be highly relevant to current debate on whether and how to fund PrEP for high-risk key populations worldwide.