Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.
Grant RM,
Lama JR,
Anderson PL,
McMahan V,
Liu AY,
Vargas L,
Goicochea P,
Casapía M,
Guanira-Carranza JV,
Ramirez-Cardich ME,
Montoya-Herrera O,
Fernández T,
Veloso VG,
Buchbinder SP,
Chariyalertsak S,
Schechter M,
Bekker LG,
Mayer KH,
Kallás EG,
Amico KR,
Mulligan K,
Bushman LR,
Hance RJ,
Ganoza C,
Defechereux P,
Postle B,
Wang F,
McConnell JJ,
Zheng JH,
Lee J,
Rooney JF,
Jaffe HS,
Martinez AI,
Burns DN,
Glidden DV;
iPrEx Study Team.
Grant R, McMahan V, Abdel-Mohsen M, Amico KR, Atchison R, Aurigemma M, Bragg L, Defechereux P, Eden C, Gagnon J, Goicochea P, Hance R, Javier J, Lee J, Levy V, Liegler T, McConnell J, Mehrotra M, Monroe-Wise A, Robles M, Schmidt T, Smith L, Stephenson S, Lama J, Vargas L, Alvarado C, Anton C, Bacilo W, Ballesteros L, Barbieri M, Chamochumbi J, Chavez S, Christen C, Cohen M, Diaz J, Egoavil R, Fajardo N, Flores R, Galvez V, Gilvonio J, Gonzales M, Gonzales M, Gonzales P, Grados E, Grant-Villegas N, Guevara M, Gutierrez R, Hernandez A, Huayhua F, Huerta C, Jacome L, Leon R, Llancare M, Llican P, Lozano K, Magallanes Y, Mamani M, Martinez K, McRae J, Mendoza Y, Meneses V, Mercado W, Morales C, Morales M, Mosquera C, Novoa J, Olortegui E, Orihuella J, Pablo K, Pachas R, Peinado J, Perez E, Porcille C, Portal G, Reque J, Rios A, Rios J, Rojas C, Rojas E, Romero C, Ruiz E, Sanchez H, Sanchez M, Seminario L, Soto R, Ticse C, Tirado M, Tume S, Vargas R, Vargas Y, Velasquez C, Vergara J, Zegarra P, Guanira JV, Ramirez ME, Aoki N, Brandes P, Calderon J, Callirgos C, Caro H, Castillo L, Castillo R, Castro L, Centenaro J, Cevallos O, Chang C, Del Castillo M, Dextre J, Diaz A, Espinoza J, Estacio J, Farfan M, Flores D, Galvez V, Ganoza C, Garcia N, Garrido M, Guerra O, Guevara ME, Huisa M, Ibañez G, Izquierdo I, Jimenez A, Juarez J, Jurupe J, Kochiu S, Lacherre M, Mantilla P, Mejia G, Meneses M, Minaya S, Mispireta S, Negron R, Noda N, Ojeda J, Padilla I, Palomino E, Peceros A, Piña P, Popuche D, Quijano E, Quino A, Quispe I, Quispe L, Ramirez B, Ramos E, Rojas G, Rojas P, Rosas G, Rosas R, Salinas C, Salinas M, Salvatierra J, Sanchez C, Sanchez L, Sanchez P, Sosa K, Soto J, Suarez Mdel C, Talaverano A, Tataje A, Tirado R, Troncos G, Urday R, Velarde E, Verastegui M, Villanueva K, Ygnacio E, Ynguil M, Casapia Morales WM, Baldeon Rios JL, Alva Montoya A, Alva Salas E, Alvarado Alvarado D, Antinori Jaen KI, Ayapi Vasquez NF, Barboza Pizango N, Bernuy Heigghen I, Calixtro Callan MA, Carbonel Villanueva KN, Casapia Morales C, Celis Estela J, Chauca Rosas M, Correa Cajachagua F, Da Costa Ahuite KK, del Castillo Panduro A, Diaz Diaz E, Estrella Grandez G, Fasabi Irarica RR, Flores Mayta AK, Garay Quiñones J, Garces Pimentel Fde M, Gomez Garcia A, Guarniz D'orazi DA, Guedes Cacique R, Guerrero Anton P, Hinojosa Boyer JC, Hoyle Ganoza LR, Huarmiyuri Zambrano A, Long Campos Y, Lopez Diaz C, Lopez Yumbato JJ, Lozano Pilco P, Maca Dávila R, Macedo Pinedo MM, Malqui Espino CA, Marin Lizarraga J, Marin Gonzales S, Medina Rengifo L, Montalvan Sandoval E, Najar Rengifo R, Navarro del Aguila I, Noronha Gomez A, Olortegui Pezantes LM, Ortiz Torres O, Panaifo Vela Rdel P, Panduro Babilonia J, Paniagua Yumbato D, Parraguez de la Cruz J, Peixoto Valdez JO, Pereyra Otrera A, Perez Ledesma D, Perez Torres I, Pezo Flores R, Puray Chavez M, Querevalu Zapata M, Quispe Churata P, Reategui Vásquez L, Reategui Tobler M, Rimachi Quiroz A, Rojas Flores C, Romero Guimack J, Ruiz Hidalgo F, Saavedra Sevillano L, Sanchez Lozano K, Sandoval Vega J, Santana C, Siche Martinez JC, Solignac Ruiz N, Tapullima Sangama A, Tapullima Upiachihua R, Tello De la Puente A, Tello Herrera JE, Tello Freitas W, Torres Barata B, Urday Ruiz B, Vela Vela C, Zevallos Molano E, Montoya-Herrera O, Fernández Cadena TE, Galarza Hinojosa LF, Abarca Caceres GR, Alava Ruiz MA, Alvarado Palma AE, Alvarado Palma RG, Alvarez Crespo VE, Andrade Teran JM, Arias Zambrano ND, Aviles Cerezo BE, Aviles Ronquillo OJ, Bajaña Granja WG, Carchipulla Almeida RJ, Casal Cabrera AM, Chicaiza Naula AM, Diaz Moran JA, Diez Pingel LR, Esparza Sarango AJ, Franco Acebo AF, García Noboa Mde L, Guiracocha Aquino LE, Heleno Reina RA, Jarrín Alvarez AA, Loor Alcivar AI, Magallanes Mansaba DD, Mattos Mattos WM, Menendez Andrade AA, Miranda Vera WR, Montaleza Tomala WH, Montero Vidal SC, Ordinola Valdiviezo JM, Palomino Alaus IC, Parrales Saldarriaga OE, Quinga Medina RM, Rivadeneira Velasco JW, Romero Barzola GA, Rosado Rodriguez DJ, Salazar Luna CM, Salinas Salinas Sdel C, Segura Alvarado DA, Suarez Luque JL, Vargas Humanante EP, Vinces Asqui HS, Yonfa Mejia JR, Zambrano Zambrano Mdel C, dos Santos VG, Freitas Lde A, de Almeida MV, de Almeida RH, Alves CA, Amaral DM, Armesto SC, Baeta Dde C, Barreto DF, Barros MB, Camacho LR, Cardoso Edos S, Cardoso SW, de Carvalho PG, de Castro CR, Cavalcanti Wde A, Cordeiro Ddos S, da Costa MD, Fernandes NM, Noé Filho M, França AN, Freitas Jda S, Friedman RK, Gama Kde S, George I, Gonzales ML, Grinsztejn B, Guimarães MR, Hoagland BR, Krstic T, Leitão FM, Lessa FC, Marques SR, Milan RC, do Monte HA, Moreira RI, Murta FC, Neto Jdos S, Neves Junior I, Nogueira Sde O, Oliveira FS, de Oliveira MS, Pedrosa M, Pessanha ES, Ribeiro VR, de Sá MA, Salgado LS, dos Santos AP Jr, dos Santos JM, dos Santos TA, Senna JR, da Silva AM, da Silva CC, da Silva SR, da Silva VO, de Souza AL, de Souza HE, de Souza LA, de Souza LH, de Souza MN, de Souza UP, de Souza Junior WJ, Torres TS, Schechter M, de Souza MB, Yoshida CB, de Aguiar DF, Alves FB, Branco KV, Brazil JC, Camara DD, da Costa MD, Faulhaber JC, Ferreira SB, Franco R, Gama PS, Garrido RQ, Hammes PC, Hernani F, Januário RJ, de Jesus Junior SC, Leal Nda S, Melo Mde F, da Silva Neto DG, Pedrosa JM, Pimentel LB, Pires Gda C, Ramos FL, Reis Ada M, Sampaio A, dos Santos AO, da Silva AJ, da Silva JR, Tebet NN, Teixeira Bde O, Telles SR, Villard M, Weinstein AL, Kallás EG, Palacios R, Araújo JA, Avelino-Silva VH, Batista AP, Bertevello D, Comello F, Correa LM, Costa PR, Dantas MC, Franco Dde L, Gambôa R, Giret MT, Menezes e Gonçalves DC, Kalil J, Kondo KT, Leal FE, Litvoc M, Maciel Ada S, Magalhães LC, Marques MH, Mathias A, de Medeiros EA, Miraglia JL, Nakagawa ZM, Paro AH, Pennachin F, Pinheiro AM, Rebelo R, Russo RT, Saraiva A, Sauer MM, Silva IM, Tarosso LF, Tomiyama H, Buchbinder S, Liu A, Gilmore HJ, Murphy K, Adams C, Arista P, Asencios JC, Blue R, Carroll S, Colvano S, Cook A, Day E, Diaz A, Faber E, Farley J, Fields S, Fuchs J, Funk S, Futeral A, Goldman M, Grant S, Holland S, Huffaker S, Irby R, Jones T, Joseph C, Koester A, Lam J, Langdon R, Levi M, Liu-Bell C, Lubensky D, Lucas L, Malloy D, Martin B, Martin Q, Matheson T, Moore C, Morrow-Hall G, Nalos AD, Nehira J, O'Campo J, Perez B, Perkins C, Quinones R, Sera R, Silberman S, Soto M, Teague A, Temelso T, Van B, White J, Wong DN, Ycasas JC, Mayer K, Chianese C, Trufant J, Alinsug C, Box M, Cole SL, Dargon J, Dunham E, Fallon M, Gelman M, Lao S, Marquez V, Maynard J, Miele R, O'Brien W, Panther L, Pechukas A, Ripton J, Rogers S, Tu D, Vanderwalker R, Chariyalertsak S, Saokhieo P, Nimsakul S, Boursuk K, Bunsoy P, Chariyalertsak C, Charuwat C, Chotirosniramit N, Chunpen K, Dokuta S, Guarnacci T, Jaithapeang K, Jongpaijitsakul P, Kaewkosaba C, Kaewpoowat Q, Kaibuddhiwat M, Keawvichit R, Ketdechar P, Khamdam P, Koottathep S, Kosashunhanan N, Kosashunhanan N, Larplertsakul A, Linpisarn S, Maneerat S, Manoyos V, Namwongprom S, Nonraban T, Panyawong P, Pasawad W, Phutthitada R, Rungruengthanakit K, Somnoi P, Songsupa R, Sroysuwan P, Sugandhaveha P, Supindham T, Techajal T, Thetket S, Tunjalern S, Tuntivate P, Visrutaratna S, Waropassagone G, Wongsrithep S, Wongthanee A, Wongworapat K, Wonkulab P, Yangnoi A, Yiamwanichaphong M, Bekker LG, Chodacki P, Scheibe A, Batist E, Frieslich H, Hosken C, Brown B, Burrell E, Farrow M, Forune N, Gcwabe L, Heiberg C, Hoffman C, Kanyemba B, Killa N, Kocsis K, Macclachla M, Machlachlan, Mannie S, Margeman A, Mark D, Mkangel M, Ndevu S, Ndobongwana C, Ndzuzo D, Nelson B, Panda B, Peters A, Qumaba M, Snyder K, Stuurman B, Fields S, Glidden D, Manzo J, McCulloch C, Mulligan K, Page K, Shiboski S, Wang F, Ahn T, Annis J, Browne L, Callies B, Carlson E, Chen D, Coblentz D, Houx P, Huff B, Larson B, Marshall T, McDonnell P, Olsen C, Ondrejcek L, Pahl D, Plusquellec S, Post J, Postle B, Prencipe J, Radkey G, Shea T, Shelhorn P, Sims A, Tran A, Van Dalfsen D, Zhang B, Bischofberger N, Clark R, Habr A, Jaffe H, Martin JC, Pfister S, Poblenz M, Rooney JF, Said F, Wulfsohn M, Young W, Burns D, Castillo B, Chow G, Csedrik J, Dieffenbach C, Dixon DO, Fanning M, Kouda A, Martinez A, Mathias C, O'Callahan M, Payton M, Proschan M, Ruiz M, Sharma U, Smith B, Zwerski S, Ferinde J, Putta N, Becker S, Eakle R, Ridzon R, Sakrison K.
Source
J. David Gladstone Institutes, University of California at San Francisco, 1650 Owens St., San Francisco, CA 94158, USA. robert.grant@ucsf.edu
Abstract
BACKGROUND:
Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.
METHODS:
We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections.
RESULTS:
The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57).
CONCLUSIONS:
Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).
- PMID:
- 21091279
- [PubMed - indexed for MEDLINE]
- PMCID:
- PMC3079639
Free PMC ArticleFigure 1Enrollment and Outcomes
The most common laboratory abnormalities that led to exclusion were elevations in hepatic aminotransferase levels, hyperbilirubinemia, and renal insufficiency. A total of 18 enrollees (0.7%) did not meet all eligibility criteria, including 2 subjects with preexisting diabetes mellitus, who were instructed to stop taking a study drug when the history was discovered. All enrolled subjects, including those who were subsequently found to be ineligible, were followed for HIV infection and safety. Quarterly-visit attendance is shown. Visits were considered to have been completed if they occurred before the subsequent visit window, with completion rates of 75 to 94% for all visits. The completion rate was more than 86% for all visits before week 132. Visits occurred within the protocol-defined window of ±5 days in 62 to 86% of visits.
N Engl J Med. 2010 December 30;363(27):2587-2599.
Figure 2Kaplan–Meier Estimates of Time to HIV Infection (Modified Intention-to-Treat Population)
The cumulative probability of HIV acquisition is shown for the two study groups. The efficacy of preexposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (FTC–TDF) was 44%, as compared with placebo (P = 0.005). The inset graph shows a more detailed version of the overall graph up to a probability of 0.10.
N Engl J Med. 2010 December 30;363(27):2587-2599.
Figure 3HIV Incidence among Subjects Receiving FTC–TDF, According to Subgroup
The efficacy of emtricitabine and tenofovir disoproxil fumarate (FTC–TDF) is 1 minus the hazard ratio. Hazard ratios of less than 1 indicate efficacy, and 95% confidence intervals (shown by horizontal lines) that do not cross 1 indicate significant evidence of efficacy. All subgroup analyses were prespecified except for testing for herpes simplex virus type 2 (HSV-2) at screening and pill use at the rate of 90%. P values for the intention-to-treat analysis and the modified intention-to-treat analysis apply to the hypothesis of any evidence of efficacy; P values for other comparisons refer to the hypothesis that efficacy differed between the two strata. NA denotes not applicable, and URAI unprotected receptive anal intercourse.
N Engl J Med. 2010 December 30;363(27):2587-2599.
Figure 4Levels of Study-Drug Components in Blood of Subjects Receiving FTC–TDF, According to HIV Status
Shown are intracellular levels (Panels A and B) and plasma levels (Panels C and D) of components of emtricitabine and tenofovir disoproxil fumarate (FTC–TDF), quantified in specimens obtained from subjects in the FTC–TDF group. FTC-TP denotes emtricitabine triphosphate, and TFV-DP tenofovir diphosphate. The horizontal lines in each panel indicate medians.
N Engl J Med. 2010 December 30;363(27):2587-2599.
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