南非威特沃特斯兰德大学Sinead Delany-Moretlwe团队研究了卡博特韦预防女性感染艾滋病的疗效。相关论文于2022年4月1日发表在《柳叶刀》杂志上。

包括许多撒哈拉以南非洲国家在内的70多个国家已经采用了暴露前口服预防艾滋病的措施，但女性在日常服药方面遇到了相当大的障碍，如耻辱感、评价和对暴力的恐惧。妇女需要安全有效的长效艾滋病毒预防药物。该研究旨在评估注射用卡博特韦与每日口服二磷酸替诺福韦加恩曲他滨（TDF-FTC）预防未感染艾滋病毒女性的安全性和有效性。

研究组在撒哈拉以南非洲七个国家的20个临床研究机构进行了一项3期临床、随机、双盲、双模拟、主动对照、优势试验，招募顺性别，年龄在18-45岁之间，报告在过去30天内至少有两次阴道性交，根据HIV风险评分有感染HIV的风险，且同意使用长效可逆预防方法的女性。

将参与者按1:1随机分配，分别接受卡博特韦联合TDF-FTC安慰剂（卡博特韦组）或TDF-FTC联合卡博特韦安慰剂（TDF-FTC组）治疗。除了负责研究产品制备的现场药剂师外，研究人员和参与者在研究组分配时双盲。

参与者在最初的4周间歇负荷后，连续5周每天口服药物，然后每8周进行一次肌肉注射，同时每日口服药片。停止注射的参与者接受开放标签每日TDF-FTC治疗48周。该研究的主要终点是意向治疗人群中的偶发HIV感染，以及至少服用一剂研究产品的所有女性中2级及以上的临床和实验室事件。

2017年11月27日至2020年11月4日，研究组招募了3224名参与者（卡博特韦组1614名，TDF-FTC组1610名）。中位年龄为25岁，3209人中有1755人（54.7%）在前一个月有两名或两名以上性伴侣。

在3898人-年期间观察到40例偶发感染，HIV发病率为1.0%；其中卡博特韦组4例（0.2例/100人-年），TDF-FTC组36例（1.85例/100人-年），组间差异显著。在405名TDF-FTC参与者的随机亚组中，1929份血浆样本中有812份（42.1%）的替诺福韦浓度与日常使用一致。

注射覆盖率为总人-年数的93%。除注射部位反应外，两组的不良事件发生率相似，卡博特韦组的不良事件发生率高于TDF-FTC组，分别为38.0%和10.7%，但并未导致停药。确定的妊娠率为1.3例/100人-年；没有先天性出生异常的报告。

研究结果表明，虽然这两种预防HIV的产品总体上安全、耐受性好且有效，但卡博特韦在预防女性HIV感染方面优于TDF-FTC。

附：英文原文

Title: Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial

Author: Sinead Delany-Moretlwe, James P Hughes, Peter Bock, Samuel Gurrion Ouma, Portia Hunidzarira, Dishiki Kalonji, Noel Kayange, Joseph Makhema, Patricia Mandima, Carrie Mathew, Elizabeth Spooner, Juliet Mpendo, Pamela Mukwekwerere, Nyaradzo Mgodi, Patricia Nahirya Ntege, Gonasagrie Nair, Clemensia Nakabiito, Harriet Nuwagaba-Biribonwoha, Ravindre Panchia, Nishanta Singh, Bekezela Siziba, Jennifer Farrior, Scott Rose, Peter L Anderson, Susan H Eshleman, Mark A Marzinke, Craig W Hendrix, Stephanie Beigel-Orme, Sybil Hosek, Elizabeth Tolley, Nirupama Sista, Adeola Adeyeye, James F Rooney, Alex Rinehart, William R Spreen, Kimberly Smith, Brett Hanscom, Myron S Cohen, Mina C Hosseinipour, Aida Asmelash, Alice Sehurutshi, Allan Baguma, Anita Marais, Barbarah Kawoozo, Bongiwe Prudence Malinga, Brenda Gati Mirembe, Brenda Okech, Bryan Esterhuizen, Caroline Murombedzi, Daphne Gadama, Eldinah Hwengwere, Elizabeth Roos, Elizabeth S Magada, Emily Shava, Estelle Piwowar-Manning, Eunice Tahuringana, Felix GS Muhlanga, Francesca Conradie, Frank Angira, Gertrude Nanyonjo, Girisha Kistnasami, Hazzie Mvula, Ishana Naidoo, Jaco Horak, Jane Jere, Jeeva Moodley, Katie Shin, Kerry Nel, Kevin Bokoch, Lilian Birungi, Lynda Emel, Maletsatsi Monametsi, Marvelous Sibanda, Mercy Mutambanengwe, Miria Chitukuta, Moleen Matimbira, Muchaneta Bhondai-Mhuri, Ncamsile Sibisi, Neetha Morar, Netsai Mudzonga, Paul Natureeba, Paul Richardson, Petina Musara, Pippa Macdonald, Rejoice Nkambule, Repelang Mosime, Rhonda White, Ribka Berhanu, Ritha Ncube-Sihlongonyane, Rogers Sekabira, Samantha Siva, Saresha Pillay, Shamelle Govender, Sheiala Bamweyana, Siyabonga Nzimande, Steve Innes, Sufia Dadabhai, Taraz Samandari, Tchangani Tembo, Thandie Lungu Mabedi, Thandiwe Chirenda, Tinashe Chidemo, Victor Mudhune, Vikesh Naidoo, Wadzanai Samaneka, Yaw Agyei, Yeukai Musodza, Yolandie Fourie

Issue&Volume: 2022-04-01

Abstract:

Background

Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women.

Methods

HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18–45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564.

Findings

From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22–30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73–1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06–0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3–2·57]; hazard ratio 0·12 [0·05–0·31]; p<0·0001; risk difference –2% [–1·3% to –2·7%]). In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9–1·7); no congenital birth anomalies were reported.

Interpretation

Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women.

DOI: 10.1016/S0140-6736(22)00538-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00538-4/fulltext