Prevention of HIV-1 infection with early antiretroviral therapy

Myron S. Cohen, Ying Q. Chen, Marybeth McCauley, Theresa Gamble, Mina C. Hosseinipour, Nagalingeswaran Kumarasamy, James G. Hakim, Johnstone Kumwenda, Beatriz Grinsztejn, Jose H S Pilotto, Sheela V. Godbole, Sanjay Mehendale, Suwat Chariyalertsak, Breno R. Santos, Kenneth H. Mayer, Irving F. Hoffman, Susan H. Eshleman, Estelle Piwowar-Manning, Lei Wang, Joseph Makhema & 15 others Lisa A. Mills, Guy De Bruyn, Ian Sanne, Joseph Eron, Joel Gallant, Diane Havlir, Susan Swindells, Heather Ribaudo, Vanessa Elharrar, David Burns, Taha E. Taha, Karin Nielsen-Saines, David Celentano, Max Essex, Thomas R. Fleming

Research output: Contribution to journalArticle

4325 Citations (Scopus)

Abstract

BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the earlytherapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

Original languageEnglish (US)
Pages (from-to)493-505
Number of pages13
JournalNew England Journal of Medicine
Volume365
Issue number6
DOIs
StatePublished - Aug 11 2011

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Virus Diseases
Secondary Prevention
HIV-1
Confidence Intervals
CD4 Lymphocyte Count
Therapeutics
National Institute of Allergy and Infectious Diseases (U.S.)
Incidence
Insurance Benefits
Primary Prevention
Pulmonary Tuberculosis
Bacterial Infections
Public Health

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cohen, M. S., Chen, Y. Q., McCauley, M., Gamble, T., Hosseinipour, M. C., Kumarasamy, N., ... Fleming, T. R. (2011). Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine, 365(6), 493-505. https://doi.org/10.1056/NEJMoa1105243

Prevention of HIV-1 infection with early antiretroviral therapy. / Cohen, Myron S.; Chen, Ying Q.; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C.; Kumarasamy, Nagalingeswaran; Hakim, James G.; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H S; Godbole, Sheela V.; Mehendale, Sanjay; Chariyalertsak, Suwat; Santos, Breno R.; Mayer, Kenneth H.; Hoffman, Irving F.; Eshleman, Susan H.; Piwowar-Manning, Estelle; Wang, Lei; Makhema, Joseph; Mills, Lisa A.; De Bruyn, Guy; Sanne, Ian; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Ribaudo, Heather; Elharrar, Vanessa; Burns, David; Taha, Taha E.; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Fleming, Thomas R.

In: New England Journal of Medicine, Vol. 365, No. 6, 11.08.2011, p. 493-505.

Research output: Contribution to journalArticle

Cohen, MS, Chen, YQ, McCauley, M, Gamble, T, Hosseinipour, MC, Kumarasamy, N, Hakim, JG, Kumwenda, J, Grinsztejn, B, Pilotto, JHS, Godbole, SV, Mehendale, S, Chariyalertsak, S, Santos, BR, Mayer, KH, Hoffman, IF, Eshleman, SH, Piwowar-Manning, E, Wang, L, Makhema, J, Mills, LA, De Bruyn, G, Sanne, I, Eron, J, Gallant, J, Havlir, D, Swindells, S, Ribaudo, H, Elharrar, V, Burns, D, Taha, TE, Nielsen-Saines, K, Celentano, D, Essex, M & Fleming, TR 2011, 'Prevention of HIV-1 infection with early antiretroviral therapy', New England Journal of Medicine, vol. 365, no. 6, pp. 493-505. https://doi.org/10.1056/NEJMoa1105243
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine. 2011 Aug 11;365(6):493-505. https://doi.org/10.1056/NEJMoa1105243
Cohen, Myron S. ; Chen, Ying Q. ; McCauley, Marybeth ; Gamble, Theresa ; Hosseinipour, Mina C. ; Kumarasamy, Nagalingeswaran ; Hakim, James G. ; Kumwenda, Johnstone ; Grinsztejn, Beatriz ; Pilotto, Jose H S ; Godbole, Sheela V. ; Mehendale, Sanjay ; Chariyalertsak, Suwat ; Santos, Breno R. ; Mayer, Kenneth H. ; Hoffman, Irving F. ; Eshleman, Susan H. ; Piwowar-Manning, Estelle ; Wang, Lei ; Makhema, Joseph ; Mills, Lisa A. ; De Bruyn, Guy ; Sanne, Ian ; Eron, Joseph ; Gallant, Joel ; Havlir, Diane ; Swindells, Susan ; Ribaudo, Heather ; Elharrar, Vanessa ; Burns, David ; Taha, Taha E. ; Nielsen-Saines, Karin ; Celentano, David ; Essex, Max ; Fleming, Thomas R. / Prevention of HIV-1 infection with early antiretroviral therapy. In: New England Journal of Medicine. 2011 ; Vol. 365, No. 6. pp. 493-505.
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abstract = "BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54{\%} of the subjects were from Africa, and 50{\%} of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95{\%} confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95{\%} CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the earlytherapy group (hazard ratio, 0.04; 95{\%} CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95{\%} CI, 0.40 to 0.88; P = 0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.)",
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AU - Cohen, Myron S.

AU - Chen, Ying Q.

AU - McCauley, Marybeth

AU - Gamble, Theresa

AU - Hosseinipour, Mina C.

AU - Kumarasamy, Nagalingeswaran

AU - Hakim, James G.

AU - Kumwenda, Johnstone

AU - Grinsztejn, Beatriz

AU - Pilotto, Jose H S

AU - Godbole, Sheela V.

AU - Mehendale, Sanjay

AU - Chariyalertsak, Suwat

AU - Santos, Breno R.

AU - Mayer, Kenneth H.

AU - Hoffman, Irving F.

AU - Eshleman, Susan H.

AU - Piwowar-Manning, Estelle

AU - Wang, Lei

AU - Makhema, Joseph

AU - Mills, Lisa A.

AU - De Bruyn, Guy

AU - Sanne, Ian

AU - Eron, Joseph

AU - Gallant, Joel

AU - Havlir, Diane

AU - Swindells, Susan

AU - Ribaudo, Heather

AU - Elharrar, Vanessa

AU - Burns, David

AU - Taha, Taha E.

AU - Nielsen-Saines, Karin

AU - Celentano, David

AU - Essex, Max

AU - Fleming, Thomas R.

PY - 2011/8/11

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N2 - BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the earlytherapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

AB - BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the earlytherapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

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