非洲育齡婦女長期使用抗反轉錄病毒治療

資料來源：www.thelancet.com/hiv / 2022 年 6 月 9 日 / 財團法人台灣紅絲帶基金會編譯

有強有力的證據顯示，對感染 HIV 的順性別育齡婦女進行抗反轉錄病毒療法 (ART) 可減少 HIV 垂直傳播並改善婦女的健康和生存。然而，缺乏在育齡婦女懷孕期間開始ART 的長期（≥5 年）影響的研究。

從 2011 年到 2016 年，來自 13 個非洲地點和一個非屬非洲地點的多國隨機臨床試驗 PROMISE 顯示，當感染 HIV 的孕婦接受 ART 組合時，HIV 垂直傳播率較低。在《刺胳針愛滋病毒》中， Taha E Taha 及其同事的後續 PROMOTE 研究開始於 2016 年，當時 PROMISE 追蹤結束。 調查人員在四個國家（包括烏干達、馬拉威、辛巴威和南非）的八個非洲地點對婦女及其子女進行了追踪調查。該研究招募了 1,987 名母親和 2,522 名兒童。 母親的中位追蹤時間為 42 個月，兒童為 36 個月。研究的留存率非常高（兒童在 42 個月時為 85%）。該研究的兩個顯著優勢是追蹤期長（使用標準照護臨床追蹤時間每 6 個月一次）和包括來自整個地區多個國家和不同環境的女性。

Taha 及其同事的結果令人鼓舞，因為它們顯示非洲順性別女性願意參與從 2010-11 年（她們最初參加 PROMISE 時）到 2021 年的長期追蹤。此外，研究人員顯示，這些感染愛滋病毒的非洲婦女在懷孕後繼續使用抗反轉錄病毒治療多年，同時在大多數研究地點的 42 個月追蹤中保持高依從性並實現高水平 (>90%) 的病毒抑制，除了馬拉威、哈拉雷（辛巴威 ) 和德班（南非）。 PROMOTE 研究顯示，失訪率極低，對 ART 的依從性很高，並且有證據顯示這些女性受益於 ART 的使用——這反映在隨著時間的推移健康指標的改善，包括高水平的生育率和自我報告的健康。此外，在隨後懷孕的婦女中，周產期 HIV 傳播率極低（報告了三例新的 HIV 周產期感染，主要是由於 ART 依從性不足）。

重要的是，研究人員對接受 ART 的女性世代進行了 3-4 年的追蹤，他們沒有發現任何重大的安全問題。 與 ART 使用相關的危及生命的事件很少見； 然而，四名孕產婦死亡可能與依非韋倫efavirenz引起的肝毒性有關。在兒童中（中位追蹤 3 年），危及生命的事件也很少見。 與大多數這些環境中愛滋病毒感染者和普通人群的背景死亡率相比，母親和兒童的死亡率都較低。

然而，這項研究強調了兩個主要的關注領域。 首先，大約 11% 的女性在上次就診時檢測到病毒載量，超過 200 名女性和 300 名嬰兒沒有在計畫中存留，可能已經失訪。次優的依從性之潛在後果（例如，垂直傳播 HIV、炎症和相關的非傳染性疾病）是令人擔憂的原因。作者預計，隨著女性改用更好的治療方案（例如正在向該地區的孕婦推廣多替拉韋dolutegravir），依從性會有所提高。其次，該研究發現某些地區（例如索韋托和烏干達）的墮胎或流產頻率相對較高。 此外，除坎帕拉（烏干達）外，所有地點的生育意願（定義為想要更多孩子）都很低，強調迫切需要在感染愛滋病毒的婦女的產後照護中提供持續的避孕服務和整合、強化的性健康和生殖健康服務。

PROMISE 和 PROMOTE 研究顯示，在撒哈拉以南非洲對母親及其嬰兒進行縱向、多國研究是可行的。 首先，這項研究對於向政策制定者提供證據顯示介入措施對於提高感染 HIV 的育齡婦女的 ART 持續性和依從性的重要性至關重要。其次，這項研究為懷孕或產後婦女提供服務的資助者和研究人員，在尋求評估新 ART 方案（例如長效 ART）、新預防技術（例如長效暴露前預防）和多重預防的縱向影響（能夠滿足多種性健康和生殖健康需求的產品）時提供了一個模型。

我申報 Gilead 的贈款和非財務支持以及 ViiV 的個人費用。

Dvora Joseph Davey djosephdavey@mednet.ucla.edu 美國洛杉磯，加州大學洛杉磯分校菲爾丁公共衛生學院傳染病學系，Geffen 醫學院流行病學系；南非開普敦，開普敦大學公共衛生學院流行病學和生物統計學系

Long-term use of ART in African women of reproductive age

www.thelancet.com/hiv Vol 9 June 2022

There is strong evidence that antiretroviral therapy (ART) for cisgender women of reproductive age living with HIV reduces vertical HIV transmission and improves women’s health and survival. However, there is a dearth of research on the long-term (≥5 years) effects of ART in reproductive-age women who started ART during pregnancy. 

From 2011 to 2016, PROMISE, a multi-country randomised clinical trial from 13 African sites and one non-African site, showed low rates of vertical HIV transmission when pregnant women living with HIV received combination ART. In The Lancet HIV, the follow-on PROMOTE study by Taha E Taha and colleagues started in 2016 when the PROMISE followup ended. Investigators followed up on women and their children in eight African sites from four countries, including Uganda, Malawi, Zimbabwe, and South Africa. The study enrolled 1987 mothers and 2522 children. The median follow-up time was 42 months in mothers and 36 months in children. Retention rates were very high in the study (85% at 42 months for children). Two notable strengths of this study were the long follow-up period (using standard of care clinical follow-up time of visits every 6 months) and the inclusion of women from multiple, diverse settings, and countries across the region. 

Taha and colleagues’ results are encouraging in that they show that African cisgender women are willing to be a part of a long follow-up period from 2010–11 (when they originally enrolled in PROMISE) to 2021. Additionally, the investigators show that these African women living with HIV continued using ART for years after pregnancy while maintaining high adherence and achieving high levels (>90%) of viral suppression at the 42 months follow-up in most study sites, except for sites in Malawi, Harare (Zimbabwe), and Durban (South Africa). The PROMOTE study showed that losses to follow-up were minimal, adherence to ART was high, and there was evidence that these women benefited from ART use—reflected in the improvement of health indicators over time, including high levels of fertility and self-reported health. Furthermore, perinatal transmission of HIV among women who had subsequent pregnancies is incredibly low (three new HIV perinatal infections were reported, mostly due to inadequate ART adherence).

Importantly, investigators followed up on the cohort of women on ART for 3–4 years and they did not identify any major safety concerns. Life-threatening events related to ART use were rare; however, four of the maternal deaths might have been associated with efavirenz-induced liver toxicity. In children (median follow-up of 3 years), life-threatening events were also rare. Mortality rates for both mothers and children were low compared with background rates in most of these settings in populations with HIV and the general population. 

However, this study highlights two primary areas of concern. First, approximately 11% of women had detectable viral load at their last visit, and over 200 women and 300 infants were not retained and might have been lost to follow-up. The potential consequences of suboptimal adherence (eg, vertical HIV transmission, inflammation, and related noncommunicable disease) are reasons for concern. The authors expect adherence to improve as women switch to better regimens, such as dolutegravir, which is being rolled out to pregnant women in the region. Second, the study found a relatively high frequency of abortions or miscarriages in some sites (eg, in Soweto and Uganda). In addition, fertility intentions (defined as wanting more children) were low across all sites, except for Kampala (Uganda), highlighting the urgent need for ongoing contraception services and integrated, strengthened sexual and reproductive health services in post-partum care for women living with HIV. 

The PROMISE and PROMOTE studies showed that longitudinal, multicountry studies of mothers and their infants are feasible in sub-Saharan Africa. First, this study is crucial to provide evidence to policy makers about the importance of interventions to improve ART continuation and adherence among women of reproductive age living with HIV. Second, this study serves as a model for funders and researchers seeking to evaluate the longitudinal impact of new ART regimens (eg, long-acting ART), new prevention technologies (eg, long-acting pre-exposure prophylaxis ), and multiple prevention technologies (products capable of addressing multiple sexual and reproductive health needs) for and with women who are pregnant or in the post-partum period.

I declare grants and non-financial support from Gilead and personal fees from ViiV. 

Dvora Joseph Davey djosephdavey@mednet.ucla.edu 

Division of Infectious Diseases, Geffen School of Medicine, Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Epidemiology and Biostatistics, School of Public Health, University of Cape Town, Cape Town, South Africa