愛滋病毒預防新時代的選擇準備
資料來源：http://www.thelancet.com/hiv Vol 10 December 2023
Gonasagrie Nair 及其同事在《剌胳針 HIV》中報告了 MTN-34/REACH 試驗的結果，該試驗調查了青春期女孩和年輕女性對 HIV 暴露前預防 (PrEP) 的安全性、依從性和偏好。 這項研究在三個非洲國家進行，採用交叉設計來獲得有關 PrEP 在該族群中使用的新見解。 16-21 歲的參與者同意分別採用每天口服恩曲他濱加富馬酸替諾福韋二吡呋酯 (oral daily emtricitabine plus tenofovir disoproxil fumarate)，和使用達匹韋林陰道環 (the dapivirine vaginal ring)，每次 6 個月。 這些 PrEP 分配的順序是隨機分配的，之後參與者過渡到 6 個月的產品選擇期，在此期間他們可以繼續使用首選的 PrEP 方式或根本不使用 PrEP。
MTN-03/REACH 試驗進行得很嚴格，在 72 週的追蹤中存留率高達 94%，令人印象深刻。 在研究過程中，產品的依從性仍然很高。 藥理學測量顯示，近 60% 的參與者每週服用四劑或更多劑量的替諾福韋二磷酸鹽濃度一致。 類似比例的達匹韋林陰道環具有與持續使用一致的殘留藥物濃度。 儘管與達匹韋林陰道環相比，口服 PrEP 期間報告的 2 級或更高級別不良事件發生率更高，但這兩種產品都是安全且耐受性良好的。 只有一位參與者正式停止研究產品（在選擇期間口服 PrEP）。 四名參與者感染了 HIV，其中兩名是在服用口服 PrEP 時感染的，兩名是在使用達匹韋林陰道環時感染的。 根據藥理學評估，所有血清轉換都發生在產品使用量低或不使用期間。
MTN-034/REACH 中納入產品選擇期（在此期間，參與者對未來PrEP 使用做出明智的選擇）提供了有關產品偏好的有趣見解，238 名參與者中的227 名(95%) 選擇繼續兩種中的某種形式的PrEP：三分之二選擇達匹韋林陰道環。 儘管 30 名 (13%) 在接下來的 6 個月內更換了產品，但最初的選擇仍然相當穩定。 鑑於迄今為止在非洲陰道環裝置的使用有限——無論是用於愛滋病毒預防、避孕還是其他適應症——這一發現有些令人驚訝。 它強調了 PrEP 的第一手經驗（在本例中是透過指定的評估期）如何引入新的交付方式，並有可能提高下游的持久性和依從性。
透過讓個人能夠選擇最符合個人需求的 PrEP 方式，產品選擇為愛滋病毒預防領域增添了一個重要的新維度。選擇對於青春期女孩和年輕女性尤其重要，這些人群在 PrEP 級聯 (cascade) 中經歷了次優結果。 例如，肯亞年輕女性和青少年 PrEP 實施計畫的結果發現，只有 16% 的少女和年輕女性接受每日提供口服 PrEP ，其中只有 29%在規劃背景下於幾週內返回補充藥物，報告的PrEP 使用率甚至更低。鑑於每日服藥面臨的挑戰有據可查，人們樂觀地認為，新配方（包括達匹韋林陰道環和注射用卡博特韋）可以直接解決PrEP 在青春期女孩和年輕婦女中使用的障礙。
撒哈拉以南非洲地區現有的 PrEP 計畫應如何實施選擇？ 可以從避孕文獻中汲取重要的教訓，幾十年來，選擇一直是提供服務的基石。 不同避孕方法的出現導致現代避孕方法普及率的提高，這是反映採用率和持續使用率的人口指標。 然而，不同選項的可用性並不會自動轉換為明智的選擇。 布吉納法索最近的一項研究發現，近40% 的避孕藥具使用者開始採用的方法與他們的偏好不符，即使他們有自己喜歡的方法。避孕藥具偏好和使用之間的不一致會增加中止的可能性和意外懷孕發生的風險。這個問題可能是由指導性諮詢引起的，指導性諮詢可能會強調提供者對使用者個人需求的信念，這損害了服務品質，並無意中助長強制動態。
為了優化愛滋病預防新時代的選擇潛力，必須將使用者的優先事項、需求和偏好置於服務提供的中心。 我們已經在努力支持以人為本的 PrEP 決策，並取得了有希望的早期成果。應完善這些決策支援工具以支援縱向決策，並進行調整以納入新的模式和表述。 最終，選擇可以成為增強 PrEP 結果的有力策略，但需要精心照顧以確保做出充分、自由和知情的決定。
LAG 獲得美國國立衛生研究院 (NIH) 透過 T32 AI007001 撥款的支持。 BHC 得到 NIH 撥款 R01 AI131060 和 R01 AI157859 的支持。 我們聲明不存在競爭利益。
Lauren A Graybill, *Benjamin H Chi benjamin_chi@med.unc.edu
北卡羅來納大學教堂山分校吉林斯全球公共衛生學院流行病學系，美國北卡羅萊納州教堂山（LAG、BHC）； 北卡羅來納大學教堂山分校醫學院婦產科，美國北卡羅來納州教堂山 (BHC)
PrEParing for choice in a new era of HIV prevention
http://www.thelancet.com/hiv Vol 10 December 2023
In The Lancet HIV, Gonasagrie Nair and colleagues report the findings from the MTN-34/REACH trial, which investigated the safety of, adherence to, and preferences for HIV pre-exposure prophylaxis (PrEP) among adolescent girls and young women. Conducted in three African countries, this study used a crossover design to gain new insights about PrEP use in this population. Participants aged 16–21 years agreed to take oral daily emtricitabine plus tenofovir disoproxil fumarate and use the dapivirine vaginal ring for 6 months each. The sequence of these PrEP assignments was randomly allocated, after which participants transitioned to a 6-month product choice period during which they could continue with a preferred PrEP modality or no PrEP at all.
The MTN-03/REACH trial was rigorously done, with an impressive 94% retention at 72 weeks of followup. Over the course of the study, product adherence remained high. Pharmacological measures show that nearly 60% of participants had tenofovir-diphosphate concentrations consistent with four or more doses per week. A similar proportion of dapivirine vaginal rings had residual drug concentrations consistent with continuous use. Both products were safe and well tolerated, although a higher frequency of adverse events grade 2 or higher were reported during oral PrEP use than with the dapivirine ring. Only one participant formally discontinued study product (oral PrEP during the choice period). Four participants acquired HIV, two while taking oral PrEP and two while using the dapivirine ring. According to pharmacological evaluations, all seroconversions occurred during periods of low to no product use.
The inclusion of the product choice period within MTN-034/REACH—during which participants made informed choices about future PrEP use—provides interesting insights about product preference 227 (95%) of 238 participants elected to continue some form of PrEP, with two-thirds selecting the dapivirine ring. Although 30 (13%) switched products over the ensuing 6 months, initial choices remained quite stable. Given the limited use of vaginal ring devices to date in Africa—whether for HIV prevention, contraception, or other indications—this finding was somewhat surprising. It highlights how first-hand experiences with PrEP, in this case through the assigned evaluation periods, can introduce new delivery modalities and potentially increase downstream persistence and adherence.
By empowering individuals to select PrEP modalities that best align with their individual needs, product choice adds an important new dimension to the field of HIV prevention. Choice might be especially important for adolescent girls and young women, a population that has experienced suboptimal outcomes across the PrEP cascade. For example, results from the PrEP Implementation for Young Women and Adolescents programme in Kenya found that only 16% of adolescent girls and young women accepted daily oral PrEP when offered and, among those individuals, only 29% returned for a refill in the weeks following initiation. In programmatic contexts, reported PrEP use has been even lower. Given well documented challenges to daily pill-taking, there is optimism that newer formulations—including the dapivirine vaginal ring and injectable cabotegravir—can directly address barriers to PrEP use among adolescent girls and young women.
How should choice be implemented into existing PrEP programmes in sub-Saharan Africa? Important lessons can be learned from the contraception literature, where choice has been a cornerstone of service delivery for decades. Availability of different contraceptive methods has led to increases in modern contraceptive prevalence, a population metric that reflects both uptake and sustained use. However, availability of different options does not automatically translate into informed choice. A recent study in Burkina Faso found that nearly 40% of contraceptive users had started a method that did not match their preferences, even when their preferred method was available. Misalignment between contraceptive preferences and use can increase the likelihood of discontinuation and risk of unintended pregnancy. This problem can be driven by directive counselling, which might emphasise provider beliefs over individual client needs, compromise service quality, and unintentionally foster coercive dynamics.
To optimise the potential of choice in this new era of HIV prevention, it is essential that client priorities, needs, and preferences are placed at the centre of service delivery. Efforts are already underway to support person-centred PrEP decision making, with promising early results. These decision support tools should be refined to support longitudinal decision making and adapted to include new modalities and formulations. Ultimately, choice can be a powerful strategy to enhance PrEP outcomes, but deliberate care is needed to ensure full, free, and informed decisions.
LAG is supported by the National Institutes of Health (NIH) through grant T32 AI007001. BHC is supported by NIH grants R01 AI131060 and R01 AI157859. We declare no competing interests.
Lauren A Graybill, *Benjamin H Chi benjamin_chi@med.unc.edu
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA (LAG, BHC); Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA (BHC)