Antiretroviral therapy for the prevention of HIV-1 transmission

M. S. Cohen, Y. Q. Chen, M. McCauley, T. Gamble, M. C. Hosseinipour, N. Kumarasamy, J. G. Hakim, J. Kumwenda, B. Grinsztejn, J. H.S. Pilotto, S. V. Godbole, S. Chariyalertsak, B. R. Santos, K. H. Mayer, I. F. Hoffman, S. H. Eshleman, E. Piwowar-Manning, L. Cottle, X. C. Zhang, J. Makhema & 16 others L. A. Mills, R. Panchia, S. Faesen, J. Eron, J. Gallant, D. Havlir, Susan Swindells, V. Elharrar, D. Burns, T. E. Taha, K. Nielsen-Saines, D. D. Celentano, M. Essex, S. E. Hudelson, A. D. Redd, T. R. Fleming

Research output: Contribution to journalArticle

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Abstract

BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1- negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

Original languageEnglish (US)
Pages (from-to)830-839
Number of pages10
JournalNew England Journal of Medicine
Volume375
Issue number9
DOIs
StatePublished - Sep 1 2016

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HIV-1
Virus Diseases
Secondary Prevention
Group Psychotherapy
Confidence Intervals
Infection
Therapeutics
CD4 Lymphocyte Count
Incidence
Acquired Immunodeficiency Syndrome
National Institute of Allergy and Infectious Diseases (U.S.)
HIV
Intention to Treat Analysis
Sexual Partners

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. (2016). Antiretroviral therapy for the prevention of HIV-1 transmission. New England Journal of Medicine, 375(9), 830-839. https://doi.org/10.1056/NEJMoa1600693

Antiretroviral therapy for the prevention of HIV-1 transmission. / Cohen, M. S.; Chen, Y. Q.; McCauley, M.; Gamble, T.; Hosseinipour, M. C.; Kumarasamy, N.; Hakim, J. G.; Kumwenda, J.; Grinsztejn, B.; Pilotto, J. H.S.; Godbole, S. V.; Chariyalertsak, S.; Santos, B. R.; Mayer, K. H.; Hoffman, I. F.; Eshleman, S. H.; Piwowar-Manning, E.; Cottle, L.; Zhang, X. C.; Makhema, J.; Mills, L. A.; Panchia, R.; Faesen, S.; Eron, J.; Gallant, J.; Havlir, D.; Swindells, Susan; Elharrar, V.; Burns, D.; Taha, T. E.; Nielsen-Saines, K.; Celentano, D. D.; Essex, M.; Hudelson, S. E.; Redd, A. D.; Fleming, T. R.

In: New England Journal of Medicine, Vol. 375, No. 9, 01.09.2016, p. 830-839.

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, Chariyalertsak, S, Santos, BR, Mayer, KH, Hoffman, IF, Eshleman, SH, Piwowar-Manning, E, Cottle, L, Zhang, XC, Makhema, J, Mills, LA, Panchia, R, Faesen, S, Eron, J, Gallant, J, Havlir, D, Swindells, S, Elharrar, V, Burns, D, Taha, TE, Nielsen-Saines, K, Celentano, DD, Essex, M, Hudelson, SE, Redd, AD & Fleming, TR 2016, 'Antiretroviral therapy for the prevention of HIV-1 transmission', New England Journal of Medicine, vol. 375, no. 9, pp. 830-839. https://doi.org/10.1056/NEJMoa1600693
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N et al. Antiretroviral therapy for the prevention of HIV-1 transmission. New England Journal of Medicine. 2016 Sep 1;375(9):830-839. https://doi.org/10.1056/NEJMoa1600693
Cohen, M. S. ; Chen, Y. Q. ; McCauley, M. ; Gamble, T. ; Hosseinipour, M. C. ; Kumarasamy, N. ; Hakim, J. G. ; Kumwenda, J. ; Grinsztejn, B. ; Pilotto, J. H.S. ; Godbole, S. V. ; Chariyalertsak, S. ; Santos, B. R. ; Mayer, K. H. ; Hoffman, I. F. ; Eshleman, S. H. ; Piwowar-Manning, E. ; Cottle, L. ; Zhang, X. C. ; Makhema, J. ; Mills, L. A. ; Panchia, R. ; Faesen, S. ; Eron, J. ; Gallant, J. ; Havlir, D. ; Swindells, Susan ; Elharrar, V. ; Burns, D. ; Taha, T. E. ; Nielsen-Saines, K. ; Celentano, D. D. ; Essex, M. ; Hudelson, S. E. ; Redd, A. D. ; Fleming, T. R. / Antiretroviral therapy for the prevention of HIV-1 transmission. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 9. pp. 830-839.
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abstract = "BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96{\%} of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1- negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9{\%}; 95{\%} confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92{\%}) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5{\%}; 95{\%} CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3{\%}; 95{\%} CI, 0.2 to 0.4). Early ART was associated with a 93{\%} lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95{\%} CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.)",
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T1 - Antiretroviral therapy for the prevention of HIV-1 transmission

AU - Cohen, M. S.

AU - Chen, Y. Q.

AU - McCauley, M.

AU - Gamble, T.

AU - Hosseinipour, M. C.

AU - Kumarasamy, N.

AU - Hakim, J. G.

AU - Kumwenda, J.

AU - Grinsztejn, B.

AU - Pilotto, J. H.S.

AU - Godbole, S. V.

AU - Chariyalertsak, S.

AU - Santos, B. R.

AU - Mayer, K. H.

AU - Hoffman, I. F.

AU - Eshleman, S. H.

AU - Piwowar-Manning, E.

AU - Cottle, L.

AU - Zhang, X. C.

AU - Makhema, J.

AU - Mills, L. A.

AU - Panchia, R.

AU - Faesen, S.

AU - Eron, J.

AU - Gallant, J.

AU - Havlir, D.

AU - Swindells, Susan

AU - Elharrar, V.

AU - Burns, D.

AU - Taha, T. E.

AU - Nielsen-Saines, K.

AU - Celentano, D. D.

AU - Essex, M.

AU - Hudelson, S. E.

AU - Redd, A. D.

AU - Fleming, T. R.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1- negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

AB - BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1- negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

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