Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.
Details
Serval ID
serval:BIB_6D90AB8B1CE0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.
Journal
The New England journal of medicine
Working group(s)
HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams
Contributor(s)
Edupuganti S., Rouphael N., Phadke V., Collins M., Cantos V.D., Del Rio C., Ignatius E.H., Kelley C.F., Summers N.A., Turbow S.D., Goepfert P.A., Overton E.T., Baden L.R., Dolin R., Johnson J.A., Seaman M.S., Walsh S.R., Gelman M.S., Krakower D., Mayer K.H., Panther L., Rodriguez B., Achong J., Calixtro M., Casapia M., Gonzales R., Hinojosa J., Quiroz A., Ramirez E., Candotti F., Christinet V., Horisberger A., Obeid M., Pantaleo G., Lama J.R., Gallardo-Cartagena J.A., Ramírez Lamas P., Sanchez J., Gonzales P., MacRae J., Cabello R., Hidalgo J.A., Clark J.L., Shoptaw S.J., Kalams S.A., Wilson G.J., Nyaku A., Swaminathan S., Morrison E., Franks J., Justman J., Mannheimer S., Wells C., Sobieszczyk M., Koblin B., Tieu H.V., Frank I., Grinsztejn B., Hoagland B., Veloso do Santos V., Villela L., Keefer M.C., Monaco C.L., Buchbinder S., Liu A., Molloy D., Norwood A., Scott H., Maenza J., McElrath J., Gay C., Hurt C., Greenberg A.E., Kuo I., Magnus M., Siegel M., Dadabhai S., Kayange N., Kumwenda J., Taha T., Garnett P., Orrell C., Singh Y., Hendricks S.L., Mokgoro M.M., Siva S.S., Spooner E., Tutshana B.O., Jeenarain N., Naidoo J., Naidoo L., Garrett N., Mahomed S., Mncwabe N.N., Naicker N., Ramdhani V., Lockman S., Makhema J.M., Masheto G., Hakim J.G., Mukwekwerere P.G., Muhlanga FGS, Mukaka S., Hunidzarira P., Mgodi N.M., Delany-Moretlwe S., Govender L., Mathew C.A., Akelo V., Tippett Barr B.A., Mboya G., Mudhune V., Oketch D., Okeyo E., Ridzon R., Samandari T., Schnabel D., Eyre C., Innes C., Senne M., Chinula L., Chunda LNG, Hosseinipour M.C., Mbichila T.H., Brits A., Grobbelaar C., Kotze S., Moraba R., Nkambule B., Pitsi A., Serehete O., Jani I.V., Ramgi P.M., Maganga L.H., William W.M., Brumskine W.L., Sein N.N., Senne M.N., Laher F., Reddy N., Sebe M., Karim Q.A., Dawood H., Khanyile M., Makhaza D., Alvarez A., Ross Zion A., Jordan C., Williams J., Xu J., Liang K., Hunt M., Bolton M., Fredrick R., Dennis R., Curate Ingram S., Nagar S., Xu J., Winter J., Harewood L., Abrams C.M., Root C.M., Powers D., Weinberg D.R., West D.R., Jobe D.D., Schaps D., Wang D., Worthington-Blount E., Wright F.G., Gharbin J., Brown J.E., Colwell J.D., Gaston K.T., Traylor K.R., Outlaw K.M., Lai L., Williams Philip O.L., Lankford-Turner P., Jalalzai R., Jaggers R.C., Regan R., Yi S., Aramgam S.L., Franks T.M., Johnson T., Lester T.T., Hunter V.L., Xu Y., Yousef A.J., Johnson C.P., Smith F.J., Logan H.L., Cunningham P.E., King S.S., James T.K., Williams T., Malemia A., Siyasiya A., Munthali A., Mwalwanda A., Chipeta B., Madiwati B., Mkwaila B., Katumbi C., Ndalama C., Gondwe D.K., Soko D.K., Marobe D., Huwa D., Bell E.S., Jere E., Goliati E., Kampira E.C., Chithila F., Mandawala F., Yamikani G.M., Anderson J., Chirwa J., Mpofu J., Makunganya J., Mayani J., Kasambala K., Degnan L., Mwafulirwa L., Seyama L., Walani M., Chadza M., Nyirenda M., Kamanga M.C., Mkandawire M., Mkamanga M., Thoko M.M., Mbilizi R., Masamba T.L., Khonyongwa W., Fabiano Z., Pandit A., Patel A., Fontana-Martinez E.J., Jin H., Kleinjan J.A., Gothing J.A., Yanosick K.E., Rao N., Izaguirre N.E., Filter R.D., Shin S.Y., Griffith A., Adams C., Kelly C.M., Chianese C., Mistretta C., Cummings D., Cardarelli G., Lam H., Sommer J.M., Dargon-Hart J., Scuzzarella J., DeFelice J., Delmonte J., Vaughan-Copeland J., Kraft J., Holmes J., Dormitzer J., Bailey K., Zinchuk K., Connal K., Michelson L., Ng L., Obradovich L., Bissell M., Estano M., Tulin M., Kus M., Camuso M., Drucker M., Kelly P., Mele R., Fish R., Tappin R., Khalid S., Buckley S., Lao S., Rugulo V., Thai V., Moyers Z.R., van der Westhuizen B., Reynolds D., Madinga N., Nozewu S., Conrad A., Clagett B., Willis B., Smith C., Moisi D., Dorazio D., Williams F., Baum J., Pasternak J., Fussell K., Banchy M., Chicchelly M., Bucklew R., Jones T., Bonin T., Rajman A., Dlungele A.P., Reddy A., Mavundla A., Phahlamohlaka B.M., Shabalala B.K., Wanda B.J., Cele B., Ndlovu B., Kubeka C.C., Cassim F., Mbuyisa F., Sithole H.V., Bhayat H.A., Sukdao J.L., Gounden J., Devnath J., Janse Van Rensburg K., Maharajh K., Woeber K., Naicker K., Baboolall L., Nzuza L.S., Thusi L., Baba L., Hlabisa L.B., Cobbing M.R., Reddy M., Buthelezi M., Magolela M., Seedat N.H., Sibisi N.T., Gcwensa N.C., Sithole N.C., Nxumalo N.F., Bhengu N., Mkhize N.S., Ngcebetsha N.Q., Luthuli NNRE, Ngcobo N., Khanyile N.H., Makhanya N.L., Mfiki N.W., Mngomezulu N.N., Gqwaru N.N., Tshabalala N.E., Jijana N.L., Guga P., Sikosana P.Y., Imamdin R., Rooyan R.T., Sibisi S., Tembe S.L., Mbokazi S., Radebe S.P., Sukazi S., Zama S.L., Dawood S., Tokota T.P., Dladla T.I., Ngidi T.S., Masikane T.E., Biyela VBS, Mathenjwa V.S., Naicker V., Bhagwandin Y., Jwara Z.G., Dladla Z., Bhoola A., Udith A.V., Dlabanta A., Mavundla A.C., Phahlamohlaka B.M., Shabalala B.K., Duma C.I., Shangase C.P., Govender D., Marx E.Y., Sayed F., Mphisa G.T., Reddy I., Naidoo J., Moodley J., Reddy J., Govender J.S., Chunderduri K., Maharaj K., Ngcobela L., Mabanga L.P., Nyirenda M., Mogkoro M.M., Reddy M., Buthelezi M.W., Ngubane M.D., Ndamase N., Ngcukana N., Morar N.S., Ngcukana N., Prosad N., Nursaye N., Hurbans N., Zungu N.P., Khanyisile N.H., Maphumulo N.Y., Nonzwakazi N., Mnqonywa M., Mthethwa N.Z., Sogoni O., Ndamase P.P., Magwaza P.D., Maduna P.V., Mvelase S., Mkhize S., Zaca S.L., Cele S., Bebeza S.A., Bhengu S., Govender S., Dawood S., Moonsamy S., Mahlase T.V., Xulu T.S., Mthembu T.S., Ndlovu T.N., Ndimande T.C., Makowa T., Gumede T.W., Hlela T.M., Sing T., Mathenjwa V.S., Chonco Z.W., Moosa A., Khuzwayo B.A., Maharaj B., Zuma BFM, Minnie C.W., Mabasa C.N., Kaunda I.F., Dias J.L., Naidoo K., Ramsaroop K.D., Ramtahal K.L., Naidoo K.P., McGowan L., Govender M., Naidoo M., Khoza N.S., Mthembu N.S., Gabela P.P., Maziya PLJ, David R., Mthiya S.S., Ngongoma S.P., Ximba S.W., Gengiah T., Nyathi T.A., Mhlongo T.G., Mkhize Z.L., Motlhanka A., Sehurutshi A., Bame B., Sankoloba B.S., Shemang B., Mdluli C., Willaims C., Gaetsaloe C., Tumagole D., Lesolobe-Masala D., Makunike E., Moseki E.M., Kadima E., Mafoko F., Molapisi G., Segatlwane I., Opelokgale KBKO, Maotonyane K., Gaebuse K., Maruatona L., Tlhaolang M., Mmolawa M.T., Mmalane M., Bhondai M., Mudojwa N., Seonyatseng N., Phirinyane N., Pule O.D., Kgakge O.J., Thabile O., Keafetole O., Monchubedi O., Elias O., Sabone P., Mosimane R.M., Madison R., Ndongwe S., Mokgweetsi S., Balosang S., Moyo S., Morapedi T., Garogwe T., Motlhanka T., Mohammed T., Mmualefhe T.T., Mokane T., Kgotla T., Frank T.T., Kebopetswe T., Sekoto T., Maiswe V., Maselwa V., Tachiona C.P., Roso C.S., Ncube E., Magada E.S., Nyakura E.C., Chivige E., Mugodhi F., Kawonza I., Musundire J., Uchirayi J., Zinyandu J., Mugari L., Chirongoma L., Machona M., Vengesai M., Waison M., Nyamhuka M., Jokonya N., Sithole N., Mufukari N., Sibanda P.N., Mahachi R., Kanyangarara S., Chiveso S., Dzaramba W., Samaneka W., Gurupira W.T., Musodza Y., Nemasango B., Siziba B., Dzidzai B., Mugocha C.C., Chitsinde C., Rushwaya C., Kawanje E., Mhizha E.S., Tahuringana E., Matsa J.M., Mandeya K., Hlahla K., Mutiti K.S., Matambanadzo K.V., Muchena M., Zhanda M., Maoko M., Chitukuta M., Mugava M., Thompson M., Nkoma M., Mhlanga N.S., Makamure P., Ndadziyira P., Kwedza R., Makondo R., Mukova S., Nyamadzawo S., Chikono S., Muvunzi T., Murefu T., Mupamombe T., Duncan V.K., Tsikiwa W.R., Matubu A.T., Chishanga A., Mufumisi A.Z., Mapfunde A., Chasakara C.Z., Chirisa C., Murandu C., Manengamambo E., Chihota E., Mhizha E., Chareka G., Dimairo J.C., Murevanhema J., Muringayi K., Samaneka L.N., Yambira MJS, Mlingo M., Zinyongo M., Sibanda M., Gwande M., Masango M., Bhondai-Mhuri M., Ngwenya N.N., Mugwagwa N., Kamanga N.E., Ruzive P.S., Dhlakama P.M., Shonhiwa R., Nyakudya S., Chibi S.N., Mutsvunguma S.P., Masuko S.I., Mafundikwa T.C., Chifambi TTL, Chinyanda T.B., Hwehwe T.D., Kufakunesu T., Chirenda T.H., Tauya T.T., Bafana T.S., Chitambo T., Nderecha WTS, Chirenje Z.M., Quino A., Isla A., Tello A., Rojas A., Rimachi A.P., Cubas A., Morey A., Urday B., Vela C., Medina C., Arredondo C., Silva C., Torres C., Ramos C., Rojas C., Rimachi D., Vela D., Pashanaste D., Ceballos E., Vega F., Chamoli G., Grandez G., López J., Panduro J., Parraguez J., Mori J., Garay J., Lozano K., Pinedo L., Ruiz L., Mowerg L., Puerta M., Del Aguila N., Torres P., Guedez R., Pezo R., Marin S., Flores T., Chikandiwa A., Kayamba F., Mashego K., Maraba M.C., Cassim N., Lebesi N., Naicker N., Menzi N.D., Ndlovu N.H., Ndzamela N.S., Diniso P., Tshandu P., Mngadi P., Bojosi P., Lenkokile R., Mogodiri T., Nyamuzhiwa T., Were A.N., Gende A., Mithika A.M., Ogendo A., Omwanda A., Nyagol B.A., Akoth B., Oyaro B., Otieno B.A., Mbeda C., Juma C., Amondi C., Ogando D., Akoko D., Awilly D., Ayuo E., Anyango E., Kerubo E., Mimba E., Awuonda E., Ouma E., Odipo E., Angira F., Oloo F., Akinyi G., Opon H.A., Kelly I., Adhiambo J., Muhanji J., Oruko J., Okanda J., Orinda J., Arego J., Wandera K.J., Makokha K.E., Obunga K., Otieno M.A., Kisera N.A., Ongwena P., Apudo P., Okech P.O., Madiega P.A., Ogutu P., Rabuogi P., Lando R., Ndivo R., Odipo R., Abwunza R., Akello R., Ouma S.G., Aremo S., Omoro T., Oloo T., Sang T., Opollo V., Sewe V., Buko Z.N., Kock A., Van A., Lakhi A.A., Dhlamini A.L., Kekana B.S., Mogakwe D.A., Janse Van Rensburg E.B., Moloko J., Market J., Baepanye K., Clark K., Baepanye K., Nhlangulela L., Collignon M., Zietsman M., Nel M., Ahmed N., Langa N., Mbipha N., Jonkane O., Mosweu P., Sanyaka P.N., Nemavhidi P., Motsatse P., Mothakga P., Nchwe S.G., Matshego S., Adonis T., Badimo T., Papalagae T., Goliath T., Mosoahle T., Matotong T., Tshikovhi V., Voidey A., Picard C., Da Silva D., Medjitna E., Tapia G., Sommer I., Molinari L., Hottinger R., Bovigny S., Decaillon T., Valera ATM, Mwaipape A., Maseko B., Kachiwaya C., Gadama D., Sichali D., Msowoya E., Kanjira F., Namalueso F., Tegha G.L., Kamwana G., Chitsulo G., Mwese J., Singogo L., Msumba L., Ndovie M., Kadiwa M., Mukatipa M., Kazembe M., Chipeta M., Chome N., Mmodzi P., Mafunga P., Mwangomba P., Kazembe R., Holla R., Nicholas S.C., Munthali T., Tembo T., Lungu T., Makuhunga T., Banda TWK, Palichina V., Ewing W., Mhango W., Kumwenda W.W., Ganoza C., Valencia J., Del Rosario Leon M., Matta M., Infante R., Magallanes Y., Amiel D., Rosas F., Sánchez H., Barbarán K.S., Alfaro R., Negron R., Pareja K., Sabaduche M., Salazar Y., Arroyo C., Blades C.E., Villanueva D., Veloz J., Briones M., Vertucci M., Thomas S.C., Reed S.E., Hernandez W., Naidoo A., Maswanganye B., Mbatha B., Chidi C., Ntlatleng F., Rampatla G., Chikeya G., Molefe L., Huyser M., van Dalen M., Mabuza N., Mhandire N., Kasselman O., Bokaba R., Rasekgwalo R., Lourens T., Mphela U., Manhice A., Massingue C.C., Castiano C.E., Fumane E.J., Cuna F., Macaringue H., Ribeiro J., Pereira K.M., Araujo K.L., Fenias L., Inhambizo L.A., Miraze M., Bule O.R., Chissumba R.M., Urio A.D., Myombe B.W., Nyiboma C.B., Kapesa E.I., Mlagalila F.F., Ambindwile J.E., Masala J.F., Lazaro L.O., Mbinda N.E., Mwilinga R.T., Kunambi R.P., Mwagobele S.A., Langlois A.J., Nochowicz C.H., King D.J., Rybczyk G.K., Rees G.M., Oleis J., Richardson K.D., Moore M.S., Alexander Q., Smith R.M., Sumner S.E., Evans T., Powell U., Sorrell V.G., Costanza C.L., Daliani C.P., Asencio E.G., Tuten J.E., Khan J.J., DeShields R.D., Rivera S.S., Love T.L., Cruz A.V., Kahn A., Swengbe J., Silverio M., Rivas M., Cavallo M., Redd R., Sondengam R., Wills A., Loquere A., Cisse I., Taj I., Cook J., Barazzuol J., Bautista J., Hinkson J., Rosario O., Gamboa R., Hirsch-Moverman Y., Rivera Y., Northland B., Gray B., Peralta H., Chang J., Benitez J., Loughlin P., Greene R., Srichankij S., Palmer S., Robertson V., Wu Y.H., Lomax A., Usher D., Lucy D., Bravo E., Ortiz G., Loeffel J., Stewart K., Strock L., Miles L., Sheikh M., Englert N., Broomes T., Vazquez T., Nandi V., Davidson A., Brown D., Dunbar D., Ho J., Kappes R., Ferreira A.C., Waite D., Lessa F., Spindola Marins L.M., Kamel L., Freitas L.A., Salgado L., Camacho L., Feitosa M., Diniz Ribeiro M.P., Morata M., Fernandes N., Rocha R., Wagner S., Nazer S., Moura S., Krstic T., Torres T.S., Teixeira Ribeiro V.R., Moran A., Bunce C.A., Gardner C., Wendt D., Smith E., Lott R., Bean S., Antenozzi S., Coughlin W., Thovhakale A.A., Motlagomang B.O., Iyemosolo B.M., Monyemangene B.D., Mabebe B.P., Modisaotsile B.M., Mashele D.T., Matsane E.D., De Klerk E., Kolobe G.K., Mataboge G.M., Mooketsi H.M., Louw I.J., Mosweu I.L., Davies I.J., Mothabanzini J.R., Isidoro L., Lekagane L.J., Theko L.C., Khoza L.S., Kgokong L.P., Kasongo M.C., Magwasha M.S., Botha M.C., Moeketsi M.M., Cwaile M.T., Molotsi M.E., Naidoo N., Sibabela N.E., Mkhize N.C., Mhandire N.K., Madikwe O.M., Mokgetsengoane P.P., Maatjie P.T., Mashele P., Maebana R.L., Lusale S.T., Mokone S.C., Shezi S.C., Nhlapo S., Vermaak S.P., Montwedi T.E., Mathode T.I., Phakathi T., Tshabile T.C., Dinake T.A., Gaoshebe T., Mogakwe T., Mosito T.M., Rameetse V.K., Manzini V.F., Diaz A., Phillips A., Shen A., Garcia A., Quan C., Samayoa D., Ng D., Chae E., Schaeffer E., O'Connell-Gates F., Green G., Asencios G., Vinson J., McGovern J., Ayankoya J., McCay K., Coleman K., Marsh K., Potter L., Lacanlale L., Henry M., Figueroa M., Ng N., Walker N., Von Felten P., Gonzalez R., Fields S., Houshangi S., Nebre S., Wagner T., Matheson T., Koplowicz Y., Konchan A., Berger D., Braun G., Lilly J., Chin J., Czartoski J., Louis K., Houdak M., Potochnic M., Morin N., Williams N., Tschumper P., Yoon R., Vadee A., Nana A., Mkhonto C., Van Heerden E., Machache G., Maseko J., Mokomele K., Kruger L., Siminya M., Mafata M.M., Masala M.P., Mahlangu N., Akoojee N., Nkosi N., Mabindisa N., Ramokoka O., Mphaphuli P., Madonsela R., Lakha R., Mashingaidze R., Govender S., Dlamini S.M., Zepe S., Mogale T., Singh U., Smith V.S., Mokwena V.O., Hlatshwayo Z., Kobane G., Slabbert N., Tlagadi A., Marx C., Pretorius L., Zikalala Z.P., Delaney A., Straub B., Shenbulo B., Soderman B., Kronk C., Evans C., Ogburn D., Barriga-Munante F., Evans G., Jackson J., Oakes J., Hancock K., Manor L., Bullis M., Furlong M., Howerton N., Maponga N., Darden-Tabb N., Pedersen S., Henderson S., Hossain T., Eldred T., Khumalo A.N., Chetty C., Mthalane E.S., Mkhize E.N., Musiello F.L., Humphries H.R., Upfold M., Samsunder N., Ndlovu N., Mchunu N.J., Mayisela N.F., Ndwandwe P.B., Ngubane S., Dhindayal S., Ndlovu S.P., Ndlovu T.F., Roberts A., Desrosiers A., King A., Nelson A., Schoonmaker A., Hunter A., Dright A., Saintilma B., Thoreson C., Knoll C., Ware C., Boone C., Parker C., Anitsakis D., Parenti D., Simon G., Akselrod H., Yellin H., Jordan J., Eyrich-Ferranti J., Mcnube J., MacNair K., Unekis K., Queen L., Balachandran M., Lintner M., Zumer M., Levy M., Turner M., Dornbush N., Swanson N., Jallah N., Abdel-Gawad N., Smergalino R., Mouton R., Wozny S., Ladson T., Mani V.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Publication state
Published
Issued date
18/03/2021
Peer-reviewed
Oui
Volume
384
Number
11
Pages
1003-1014
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.
We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC <sub>80</sub> ) of acquired isolates was measured with the TZM-bl assay.
Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC <sub>80</sub> <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates.
VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).
We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC <sub>80</sub> ) of acquired isolates was measured with the TZM-bl assay.
Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC <sub>80</sub> <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates.
VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).
Keywords
Adolescent, Adult, Africa South of the Sahara/epidemiology, Americas/epidemiology, Antibodies, Monoclonal/adverse effects, Antibodies, Monoclonal/therapeutic use, Broadly Neutralizing Antibodies/adverse effects, Broadly Neutralizing Antibodies/therapeutic use, Double-Blind Method, Europe/epidemiology, Female, HIV Antibodies/adverse effects, HIV Antibodies/therapeutic use, HIV Infections/epidemiology, HIV Infections/prevention & control, HIV-1/drug effects, Humans, Incidence, Male, Proof of Concept Study, Young Adult
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Web of science
Create date
25/05/2021 10:53
Last modification date
26/05/2021 6:35