Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial.
Connie Celum,Anna Wald,Barbara Steele,Damon R Jameson,George Froehle,Troy Sexton,Nina Kim,Erin Lennon,Nancy Stoaks,William L H Whittington,Darcie Somera,Matt Leidholm,Linda Barnes,Jairam R Lingappa,Jared M Baeten,Meeili Huang,Rhoda Ashley Morrow,Matthew R Golden,Mary Manyara,Gladys Kembo,Lameck Manhembe,Richard Makuzva,Bridget Shaishei Chikosi,Zephania Mazula,Irene Zuyu,Stella Kandemiri,Daylight Sanyanga,Samuel Gavi,Zambia Stewart E Reid,Tami Ito,Moses Sinkala,Elizabeth Biemba,Agnes Nondo,Joyce Mapanza,Sara Phiri,Priscilla Chola,Mavis Mwale,A E Taylor,Martha Phiri,Rachael Ngulube,Pauline Musumali,Justina Lubasi,Catherine Phiri,Margaret Kamanga,Elizabeth Rice,Bernice Mwale,Faustina Makiko,Daisy Mwaba,Patrick Chipaila,Francis Soko,Gilbert Banda,Francis Tafirenyika,Mable Kunka,Kelvin Nyambe,Mwila Mambwe,Hawkins Chimfutumba,Idah Moya Phiri,Ireen Zulu,Loveness P Kalemba,Evelyn Chilufya,Beauty K Savita,Emelia Sunkutu,Esther Ndhlovu,Elizabeth Nonde,Chanda Mabel Banda,Patricia M Kekelwa,Mike Ngulube,E Banda,Irene Kapasa Nyirenda,Angelina Tembo,Stella Malowa,Emeldah Mhango,Giveness M Miti,Mercy Mwale Zimba,Nivea C Mwale,Elizabeth N Tembo,Bibian N Simbeya,Thabiso Maseko Phiri,Theresa Mutale,Fredrick Mtonga,Caroline Chikoko,Judith Chipaya,Mwase Mulenga,Jonathan Fuchs,A Aguilar,Jose Carlos Asencios,Robert Wilder Blue,Scott Carroll,Sarah Colvario,Alfonso Diaz,David Diaz,Beth Faraguna,J Farley,Justin Franz,Anjali Garg,Sally Grant,Susan Guerrero,Kathleen Hentz,Travis Hottes,Sally Holland,Beverly Jackson,Pravina V Kittredge,Antonio Kruger,Bahar Kumar,Jennifer Lam,Rachel Langdon,Irene Lee,Albert Liu,Erika Molina,Corvette Moore,Gavin Morrowhall,Blake Nemec,J F Ocampo,Chris Powers,Yan Ping Qi,Jennifer Sarche,Abby Sorensen,Amy Vieira,Janie Vinson,T E Wagner,S Wheeler,Brett Gray,Carolyn Booher,D M Goodman,Guozhen Xu,Jason Santiago,Jay Loeffel,John Bonelli,Jonathan Brown,Kent Curtis,Krista Goodman,Leah Strock,Louise Austin,Lynne Bartell,Michael Camacho,Miguel Angel Hernandez Rivera,Nikki Englert,O Gonzalez,Sean Lawrence,Thomas Lee,J Ojeda,Julio Espinoza,Carolina Hennings,Juan Guanira,Pedro Goicochea,Aldo Lucchetti,Carmela Ganoza,Pedro Gonzales,Jesus Peinado,Oscar Guerra,Vergara Jorge,Eberth Quijano,C F Mosquera,M Guevara,Patricia Segura,M C Sanchez,G Rosas,J G Ariza,Julio Dextre,Diana Flores,I Gomez,Sara Tume,Mylena Tirado,Julio Prado,Oscar Cevallos,Peter Brandes,Bertha Talaverano,Jose Calienes,Miguel Morales,Juan Estacio,J A Jimenez,C H Morales,Eduardo Ruiz,G Gonzalez Diaz,Silvana Quiroz,Indira Quispe,Norma Noda,Cecilia Chang,Dina Popuche,Giovanna Solis,Carmen Salinas,Ruller Soto,Michelle Huisa,Ronny Tirado,M T Martin Patino,Carlos Romero,J Mora,Ruben Castillo,Rosario Leon,Hugo Sanchez,Edgar Grados,Rafael Rosas,Alex Jimenez,Jonathan Zamora,Miguel Bayona,Ivan Gonzales,Luis Flores Castillo,L I Romero,Xavier Rojas,Rafael Egoavil,Jorge Gonzales,Augusto Navarro,Carlos Alvarado,Edwin Palomino,Armando A Rodriguez,Giuliano Rojas,Carlos Montesino,Edgar Huerta,Abner Ortiz,Juan Carlos Hurtado,Mirna Garrido,Rocio Villavicencio,Silvia Sandoval,Ada Villavicencio,Rodrigues Julio,Julissa Bautista,R A Perdomo,Luis Gras Garcia,Olaf Venegas,Hector Montoya,Martin Casapia,Juan Carlos Hinojosa Boyer,Alberto H Quino,Bertha Ramirez,Marco Calixtro,L Mendoza,Madeleine Montoya Perez,Norma Pezo Mejia,Debora Alvarado Alvarado,Bessy Ferreira Yong,Julissa Garay,Sonia Minaya Toledo,Martin Querevalu Zapata,S Gonzales,S Aguila,Ivonne Navarro Del Aguila,Lucia Ruiz Escalante,Julio Sandoval Vega,Carlos Vela Vela,O Torre,Renato Guedez Cacique,Luis Medina Rengifo,Angel Alva Montoya,Rafael Maca Davila,Jorge Pezo,Bernadette Beatrice Nkosi,Gugu Tshabalala,Mary Edwards,Sinead Delanymoretlwe,Helen Rees,Francois Venter,Sibongile Motloung
The Lancet（2008）
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摘要
Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition.We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00076232.3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1.16 [95% CI 0.83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0.53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). We recorded no serious events related to the study drug.Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.
