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N Engl J Med. 2010 Feb 4;362(5):427-39. doi: 10.1056/NEJMoa0904849. Epub 2010 Jan 20.

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

Collaborators (590)

Celum C, Wald A, Lingappa J, Magaret A, Hughes JP, Corey L, Baeten JM, McElrath MJ, Bakari B, Barnes LS, Brantley J, Broad J, Durbin S, Farley P, Farrell-Ross M, Flores C, Haugen H, Heffron R, Jackson A, Jonnalagadda SR, Kahle E, Karas J, Karschney R, Kidoguchi L, Kline K, Krows M, Leidholm M, Lennon E, Maddox T, McVarish L, Mobley A, Morrison S, Mugo N, Mujugira A, Nayani V, Ndase P, Nelson K, Newbold T, Panteleeff D, Perera D, Richmond K, Rose A, Shaffer K, Shah H, Sniffen S, Somera D, Stoaks N, Thomas K, Tran C, Wang R, Wang S, Warner-Lubin M, Wilcox E, Wilson C, McKay A, Coetzee D, Kamupira M, de Kock A, Godwana S, Gogo L, Huna J, Khume K, Lee Z, Lindsey S, Mabuto N, Magona P, Makanyiseli M, Makhonza N, Makola N, Mazula Z, Nkompela T, Nkwateni M, Ntshongwana M, Patel S, Tshabalala M, Tshangela L, Tshingana L, Fife K, Were E, Apaka C, Nzioka S, Achieng C, Akhaabi P, Ayuo P, Baliddawa J, Barasa F, Cheruiyot J, Cheruiyot R, Dorothy M, Francis O, Godfrey K, Jaleny O, Kaguiri E, Kamotho H, Kapere C, Kennedy M, Komen A, Kosgei J, Mbowo E, Melli B, Mudogo F, Muga J, Mungai G, Murgor N, Muthui G, Njiru H, Odhiambo C, Ogallo E, Ogolla W, Oketch D, Pierre M, Roseirene M, Rugut J, Saruni J, Sawe J, Seronei S, Sidle J, Simiyu G, Thumbi M, Wafula M, Wamalwa E, Wools-Kaloustian K, Essex M, Makhema J, Ndase P, Dusara-Muzenda P, Owor A, Abel C, Baitseng T, Bome NB, Ekezie C, Hambira R, Iketleng T, Joseph M, Keothepile K, Kgafela M, Kusane A, Madison R, Malamba M, Manyiwa E, Maotwe T, Masike O, Mbazo O, Modise G, Modise G, Mongwa W, Mooketsi U, Mooketsi R, Mosarwe B, Moyo S, Moyo K, Musarira F, Musonda R, Ndungu T, Ntshimane M, Nyawe T, Holme MP, Radinku T, Rammidi K, Sekoto T, Sepako E, Serojane F, Thior I, Widenfelt E, Katabira E, Ronald A, Kavuma L, Bambia F, Brown C, Bulya N, Byabasheija R, Izizinga D, Joloba ML, Kajumba B, Kibuuka E, Kibuuka G, Kikulwe R, Kiranda R, Kirimunda S, Kisekka R, Kizza DM, Kyagaba M, Luzze R, Magala JM, Mugwanya K, Musoke R, Musingunzi AP, Mutyoba J, Muwanguzi J, Muwanguzi P, Nabwire J, Najjta B, Nakanwagi P, Nakku-Joloba E, Nakyanzi A, Namagembe D, Nambi F, Nampala MR, Ntege RP, Odongo P, Okello M, Okwero E, Owor L, Sebikejje R, Ssebbaale A, Tamale ZB, Wasubire J, Allen S, Kayitenkore K, Karita E, Bekan B, Kelley A, Bavana B, Ingabire C, Kabera E, Karangayire P, Linton S, Mudidi E, Mukamuyango J, Mukeshimana J, Mushikiwabo A, Musoni JL, Nsabimana AP, Nshimiyimana A, Nyirabagwiza C, Rufagari J, Sebahungu F, Bukusi E, Cohen C, Nduba V, Odoyo J, Achando J, Achola MA, Adhiambo PP, Adhiambo J, Adipo M, Agot K, Akinyi E, Aluoch AA, Asol F, Bonareri L, Bwoga M, Dacha E, Dola T, Josephine M, Kasyoki J, Kibatha M, Kimani P, Koech D, Kulzer J, Kwach V, Kwena T, Memo LA, Moraa I, Muga C, Mwake P, Mwangi P, Ndichu SN, Ng'oma LA, Njeru E, Nyang'wara L, Nyanjage A, Obiero A, Ochieng D, Ochieng A, Ochuka B, Odera EO, Odhacha J, Odipo C, Odondi J, Odula L, Ogembo S, Ogolo J, Okello D, Okello A, Okeyo R, Okombo M, Okumu LA, Olwenge P, Ombelu FO, Omonge M, Ondiek F, Onyang' J, Onyango P, Onyango B, Ooko H, Opondo C, Orwa J, Osese H, Osir N, Osoo J, Otieno A, Otieno BA, Owiti JA, Raminya J, Rono B, Sharma N, Shiteka R, Wakhungu IN, Wamae N, Wandiga S, Allen S, Kanweka W, Blacher R, Banda A, Beyer A, Bwembya N, Chanda MM, Chanda M, Chibwe H, Chibwe MN, Cluck H, Kaetano L, Kafwaka M, Kapatiso BK, Kasonga W, Kolala I, Lambdin B, Masedza J, Mukuka P, Mulongoti L, Munene C, Musonda GM, Mutiti M, Mutwale D, Namafente C, Ndhlovu J, Nyoni IM, Phiri B, Sakala M, Shah H, Silumesi P, Veal L, Allen S, Vwalika B, Blacher R, Henderson F, Aikayo R, Aikayo F, Besa S, Chitambi A, Chitambi R, Katongo M, Keeling M, Matoba C, Mulenga M, Musonda B, Musonda S, Musulwe L, Mweemba S, Mwila C, Ndhlovu D, Shansonga M, Sharkey T, Shumba H, Kapiga S, Manongi R, Magao P, Imeru A, Swai M, Assenga C, Bamba B, Gonzales AD, Mbwambo MJ, Kessy G, Kidella M, Tillya SM, Makyao H, Maliwa E, Mallya E, Mandao B, Maro V, Maro F, Masaki M, Mbuya E, Bengesi HM, Mlay A, Mosha S, Mrawa M, Mrema H, Mrema G, Msabaa J, Msuya A, Mushi G, Ngilangwa D, Olotu I, Otaru M, Riwa V, Samba T, Tamilwai SS, Temu L, Farquhar C, John-Stewart G, Kiarie J, Tamooh H, Gichuhi S, Kinuthia J, Morrison S, Abkallo H, Akinyi C, Brahmbhatt S, Gitonga E, Idala S, Kamau J, Kamoni R, Karanja J, Kebaara M, Keino S, Keli-Kariithi F, Kibatha M, Kinoti F, Kinyua M, Ludenyo V, Maina S, Makhoha EN, Malubi J, Mose F, Mugo D, Mukundi L, Mulinge L, Mulwa BM, Mureithi J, Mutie L, Mutiso W, Ndungu C, Ngugi M, Nindo F, Njoroge S, Njuguna E, Obara WO, Obuya C, Ogallo J, Okoth NA, Onyanyo R, Opiyo N, Otachi J, Oweya E, Swaleh F, Thiongo A, Timko M, Wachira M, Wafula A, Wairimu M, Wamuyu C, Waweru M, Yegon J, Allen S, Inambao M, Wong F, Bhebhe JB, Chilimboyi K M, Chinyama J, Chinyama L, Chisankuta F, Chileshe P, Cox G, Daka J, Gilbert Y, Kabwe I, Kyakilika E, Linton S, Malauni-Nkhoma P, Maleya C, Masase CH, Mulaisho SC, Mulumbwa W, Mushili T, Mwale M, Shacholi M, Simbala F, Delany-Moretlwe S, Rees H, Mlaba N, Maduna M, Adu-Sarkodie Y, Akpomiemie G, Arjun J, Francisco G, Gegana N, Govuzela S, Mabasa D, Madi M, Makambi V, Makau Z, Manaka M, Manamela P, Maseko P, Mashapa T, Maswanganyi M, Mdaka K, von Mollendorf C, Moyes J, Ngobeni K, Readhead A, Ngobeni K, Suping N, Shongwe Z, Tsholwana M, de Bruyn G, Gray G, McIntyre J, Dhlamini P, Bandezi N, Kowo SD, Robertson G, Chhiboo R, Jele Z, Lumko L, Madima C, Majola N, Mathole M, Matshe M, Maphiri Z, Masilo N, Modiadie R, Montso P, Moodley D, Motlamelle M, Mphafudi T, Mphaka N, Nobangela L, Seabelo T, Sibeko N, Tshabalala G, Vilakazi N, Mugo NR, Ngure K, Boro N, Chege H, Iguna S, Irungu E, Kinyoki A, Mburu S, Michira P, Musingila P, Mutungi M, Mwaniki P, Mwathi J, Nyaga V, Nyokabi J, Ochogo G, Ongachi S, Wangari A, Wanjala R, Stevens W, Jentsch U, Ingram C, van den Heuvel J, Booley M, Bulbulia F, Ondrejcek L, Pahl D, Postle B, Berman R, Ahn T, Callies B, Coblentz D, Curtis B, Olsen C, Radkey G, Schulte J, Shah H, Shea T, Mullins JI, Campbell MS, Deng W, Raugi D, Sorensen S, Stoddard J, Wong K, Zhao H, Whittington W, Xet-Mull AM, Coombs RW, Dragavon J, Daza G, Ortega JP, Scherrer MC, Corey L, Morrow RA, Kuypers J, Cent A, Diem K, Huang ML, Nguyen P, Pepper G, Sampoleo R, Hayes TS, Selke S, Zimmerman C.

Author information

  • 1Department of Global Health, University of Washington, Harborview Medical Center, 325 Ninth Ave., Box 359927, Seattle, WA 98104, USA.

Abstract

BACKGROUND:

Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1.

METHODS:

We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses.

RESULTS:

A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed.

CONCLUSIONS:

Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

2010 Massachusetts Medical Society

Comment in

PMID:
20089951
[PubMed - indexed for MEDLINE]
PMCID:
PMC2838503
Free PMC Article

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