Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women
Annalene Nel, Neliëtte van Niekerk, Saidi Kapiga, Linda-Gail Bekker, Cynthia Gama, Katherine Gill, Anatoli Kamali, Philip Kotze, Cheryl Louw, Zonke Mabude, Nokuthula Miti, Sylvia Kusemererwa, Hugo Tempelman, Hannelie Carstens, Brid Devlin, Michelle Isaacs, Mariëtte Malherbe, Winel Mans, Jeremy Nuttall, Marisa Russell, Smangaliso Ntshele, Marlie Smit, Leonard Solai, Patrick Spence, John Steytler, Kathleen Windle, Maarten Borremans, Sophie Resseler, Jens Van Roey, Wim Parys, Tony Vangeneugden, Ben Van Baelen, Zeda Rosenberg, Ring Study Team, Sieglinde Kruger, Hanlie Veldsman, Leonie Jansen Van Vuuren, Cathy Neate, Nomhle Mabuza, Marthie De Villiers, Alinah Masiu, Lena Masombuka, Christina Bodigelo, Rose Masilo, Themba Mema, Jane Mashigo, Boitumelo Milanzi, Christina Olivier, Martha Martins, Lorraine Shibambu, Christinah Phalali, Diana Motshweni, Brenda Khoza, Emma Hlaletwa, Julia Kekana, Selina Mashabane, Nomonde Sibabela, Mamphi Mafoka, Mavis Senne, Lungi Khuzwayo, Thando Patience Gwetu, Mthokozisi Ngxongo, Sphilile Xulu, Nozipho Shabalala, Thobeka Lebenya, Sifiso Buthelezi, Sbonelo Phakathi, Marlene Naidoo, Duduzile Lembethe, Bongiwe Rose Nxele, Mandisa Pearl Mlangeni, Thobile Getrude Mhlongo, Noluthando Nomkhosi Mkhize, Gugu Ndlovu, Mpumelelo Mabhida, Thobile Dlamini, Portia Qiniso Khanyile, Sibusiso Mkhize, Bathobile Myeza, Thuleleni Mildred Dlungwane, Nonkululeko Angel Tesfay, Judith Lethiwe Ndlela, Primrose Sindile Ndlovu, Nontobeko Sosibo, Sydney Sibiya, Sushellwathee Behariram, Patrick Nkosi, Jill Felce, Mirranda Mhlongo, Jacqueline Hills, Prenita Sooknannan, Brian Groenewald, Liesbeth Groenewald, Zaheda Ismail, Sharitha Prethepal, Thandeka Sibisi, Desire Bell, Nadia McMaster, Carmen Schmuhl, Kalyani Mudeliar, Lungile Mbuyisa, Nokulunga Khanyile, Nomaswazi Dlamini, Vera Chonco, Thandazile Myeza, Marjorie Sithole, Nakile Mabaso, Fakazile Thwala, Ntombinthathu Mthethwa, Lugile Mazibuko, Nonhlanhla Hlongwane, Hlengiwe Zwane, Nonhlanhla Hadebe, Victoria Zondi, Thembisele Ndaba, Penelope Mabizela, Sithabisa Jele, Andile Thusi, Nombulelo Mjiyakho, Busisiwe Makhaya, Philisile Khambule, Eugene Ruzagira, Vincent Basajja, Sophie Nalutaaya, Richard Mawogole, Kitumba Joseph, Ssemaganda Henry, Victoria Mugwaneza, Richard Rwanyonga, Diana Nakitto Kesi, Paul Taire, Ubaldo Bahemuka, Freddie Mukasa Kibengo, Margaret Kalibbala, Andrew Abaasa, Emanuel Aling, Peter Hughes, Jael Issabella Nakalema, Sarah Nakato, Josephine Bayigga, Martin Onyango, Faith Allen Namutosi, Andrew Walungama Kiyingi, Anita Kabarambi, Gloria Bahizi, Regina Nanyunja, Kenneth Mawanda Collins, Irene Nassuuna, Sylvia Masawi, Faith Naddunga Ruth, Beatrice Kimono Washi, Penelope Akankunda, Sureyah Nassimbwa, Paul Mayanja, Leah Mbabazi, Agnes Nakkazi Bukenya, Moses Kwizera, Joyce Nabunnya Tumwiine, Nalubowa Christine, Lucy Luyiga, Namirembe Aeron, Tobias Baga Vudriko, Muhigirwa Edward, Mushabe Didas, Lameze Witbooi, Nadine Diedericks, Keshani Naidoo, Peggy Tobata, Owethu Mahali, Linda Lifson, Janice Wallace, Nosipho Mncwabe, Ntombomzi Mcanjana, Hilda Ntjana, Nokupiwa Mahoyi, Ntombozuko Ngetu, Bonga Mithi, Buyiswa Ntsadu, Tembisa Nkompela, Busiswe Ngqola, Thabisa Maqweqwana, Andiswa Gidana, Kelebogile Seloka, Nomvuyiso Wadi Dyani, Robert Moraba, Larissa de Boer, Herbert Bolotini, Ndoda Mnqayi, Tholakele Mathe, Milliah Hlathi, Frans Tema, Cedric Ditshego, Suzan Masemola, Selinah Madihlaba, Hellen Mokoena, Ambros Mashishi, Johannah Hlongoane, Lourens Duvenhage, Robert Myeridricks, Renee Meyer, Masello Mohlala, Charlotte Mphake, Mabel Masha, Annalene Nel, Neliëtte van Niekerk, Saidi Kapiga, Linda-Gail Bekker, Cynthia Gama, Katherine Gill, Anatoli Kamali, Philip Kotze, Cheryl Louw, Zonke Mabude, Nokuthula Miti, Sylvia Kusemererwa, Hugo Tempelman, Hannelie Carstens, Brid Devlin, Michelle Isaacs, Mariëtte Malherbe, Winel Mans, Jeremy Nuttall, Marisa Russell, Smangaliso Ntshele, Marlie Smit, Leonard Solai, Patrick Spence, John Steytler, Kathleen Windle, Maarten Borremans, Sophie Resseler, Jens Van Roey, Wim Parys, Tony Vangeneugden, Ben Van Baelen, Zeda Rosenberg, Ring Study Team, Sieglinde Kruger, Hanlie Veldsman, Leonie Jansen Van Vuuren, Cathy Neate, Nomhle Mabuza, Marthie De Villiers, Alinah Masiu, Lena Masombuka, Christina Bodigelo, Rose Masilo, Themba Mema, Jane Mashigo, Boitumelo Milanzi, Christina Olivier, Martha Martins, Lorraine Shibambu, Christinah Phalali, Diana Motshweni, Brenda Khoza, Emma Hlaletwa, Julia Kekana, Selina Mashabane, Nomonde Sibabela, Mamphi Mafoka, Mavis Senne, Lungi Khuzwayo, Thando Patience Gwetu, Mthokozisi Ngxongo, Sphilile Xulu, Nozipho Shabalala, Thobeka Lebenya, Sifiso Buthelezi, Sbonelo Phakathi, Marlene Naidoo, Duduzile Lembethe, Bongiwe Rose Nxele, Mandisa Pearl Mlangeni, Thobile Getrude Mhlongo, Noluthando Nomkhosi Mkhize, Gugu Ndlovu, Mpumelelo Mabhida, Thobile Dlamini, Portia Qiniso Khanyile, Sibusiso Mkhize, Bathobile Myeza, Thuleleni Mildred Dlungwane, Nonkululeko Angel Tesfay, Judith Lethiwe Ndlela, Primrose Sindile Ndlovu, Nontobeko Sosibo, Sydney Sibiya, Sushellwathee Behariram, Patrick Nkosi, Jill Felce, Mirranda Mhlongo, Jacqueline Hills, Prenita Sooknannan, Brian Groenewald, Liesbeth Groenewald, Zaheda Ismail, Sharitha Prethepal, Thandeka Sibisi, Desire Bell, Nadia McMaster, Carmen Schmuhl, Kalyani Mudeliar, Lungile Mbuyisa, Nokulunga Khanyile, Nomaswazi Dlamini, Vera Chonco, Thandazile Myeza, Marjorie Sithole, Nakile Mabaso, Fakazile Thwala, Ntombinthathu Mthethwa, Lugile Mazibuko, Nonhlanhla Hlongwane, Hlengiwe Zwane, Nonhlanhla Hadebe, Victoria Zondi, Thembisele Ndaba, Penelope Mabizela, Sithabisa Jele, Andile Thusi, Nombulelo Mjiyakho, Busisiwe Makhaya, Philisile Khambule, Eugene Ruzagira, Vincent Basajja, Sophie Nalutaaya, Richard Mawogole, Kitumba Joseph, Ssemaganda Henry, Victoria Mugwaneza, Richard Rwanyonga, Diana Nakitto Kesi, Paul Taire, Ubaldo Bahemuka, Freddie Mukasa Kibengo, Margaret Kalibbala, Andrew Abaasa, Emanuel Aling, Peter Hughes, Jael Issabella Nakalema, Sarah Nakato, Josephine Bayigga, Martin Onyango, Faith Allen Namutosi, Andrew Walungama Kiyingi, Anita Kabarambi, Gloria Bahizi, Regina Nanyunja, Kenneth Mawanda Collins, Irene Nassuuna, Sylvia Masawi, Faith Naddunga Ruth, Beatrice Kimono Washi, Penelope Akankunda, Sureyah Nassimbwa, Paul Mayanja, Leah Mbabazi, Agnes Nakkazi Bukenya, Moses Kwizera, Joyce Nabunnya Tumwiine, Nalubowa Christine, Lucy Luyiga, Namirembe Aeron, Tobias Baga Vudriko, Muhigirwa Edward, Mushabe Didas, Lameze Witbooi, Nadine Diedericks, Keshani Naidoo, Peggy Tobata, Owethu Mahali, Linda Lifson, Janice Wallace, Nosipho Mncwabe, Ntombomzi Mcanjana, Hilda Ntjana, Nokupiwa Mahoyi, Ntombozuko Ngetu, Bonga Mithi, Buyiswa Ntsadu, Tembisa Nkompela, Busiswe Ngqola, Thabisa Maqweqwana, Andiswa Gidana, Kelebogile Seloka, Nomvuyiso Wadi Dyani, Robert Moraba, Larissa de Boer, Herbert Bolotini, Ndoda Mnqayi, Tholakele Mathe, Milliah Hlathi, Frans Tema, Cedric Ditshego, Suzan Masemola, Selinah Madihlaba, Hellen Mokoena, Ambros Mashishi, Johannah Hlongoane, Lourens Duvenhage, Robert Myeridricks, Renee Meyer, Masello Mohlala, Charlotte Mphake, Mabel Masha
Abstract
Background: The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda.
Methods: In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion.
Results: A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P=0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P=0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified.
Conclusions: Among women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226 .).
Source: PubMed