Short-course antiretroviral therapy in primary HIV infection

Sarah Fidler, Kholoud Porter, Fiona Ewings, John Frater, Gita Ramjee, David Cooper, Helen Rees, Martin Fisher, Mauro Schechter, Pontiano Kaleebu, Giuseppe Tambussi, Sabine Kinloch, Jose M. Miro, Anthony Kelleher, Myra McClure, Steve Kaye, Michelle Gabriel, Rodney Phillips, Jonathan Weber, Abdel Babiker

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Abstract

BACKGROUND: Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. METHODS: We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. RESULTS: A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P = 0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P = 0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P = 0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log10 copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. CONCLUSIONS: A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.)

Original languageEnglish
Pages (from-to)207-217
Number of pages11
JournalNew England Journal of Medicine
Volume368
Issue number3
DOIs
Publication statusPublished - Jan 17 2013

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Virus Diseases
HIV
Therapeutics
Confidence Intervals
CD4 Lymphocyte Count
Group Psychotherapy
Disease Progression

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fidler, S., Porter, K., Ewings, F., Frater, J., Ramjee, G., Cooper, D., ... Babiker, A. (2013). Short-course antiretroviral therapy in primary HIV infection. New England Journal of Medicine, 368(3), 207-217. https://doi.org/10.1056/NEJMoa1110039

Short-course antiretroviral therapy in primary HIV infection. / Fidler, Sarah; Porter, Kholoud; Ewings, Fiona; Frater, John; Ramjee, Gita; Cooper, David; Rees, Helen; Fisher, Martin; Schechter, Mauro; Kaleebu, Pontiano; Tambussi, Giuseppe; Kinloch, Sabine; Miro, Jose M.; Kelleher, Anthony; McClure, Myra; Kaye, Steve; Gabriel, Michelle; Phillips, Rodney; Weber, Jonathan; Babiker, Abdel.

In: New England Journal of Medicine, Vol. 368, No. 3, 17.01.2013, p. 207-217.

Research output: Contribution to journalArticle

Fidler, S, Porter, K, Ewings, F, Frater, J, Ramjee, G, Cooper, D, Rees, H, Fisher, M, Schechter, M, Kaleebu, P, Tambussi, G, Kinloch, S, Miro, JM, Kelleher, A, McClure, M, Kaye, S, Gabriel, M, Phillips, R, Weber, J & Babiker, A 2013, 'Short-course antiretroviral therapy in primary HIV infection', New England Journal of Medicine, vol. 368, no. 3, pp. 207-217. https://doi.org/10.1056/NEJMoa1110039
Fidler S, Porter K, Ewings F, Frater J, Ramjee G, Cooper D et al. Short-course antiretroviral therapy in primary HIV infection. New England Journal of Medicine. 2013 Jan 17;368(3):207-217. https://doi.org/10.1056/NEJMoa1110039
Fidler, Sarah ; Porter, Kholoud ; Ewings, Fiona ; Frater, John ; Ramjee, Gita ; Cooper, David ; Rees, Helen ; Fisher, Martin ; Schechter, Mauro ; Kaleebu, Pontiano ; Tambussi, Giuseppe ; Kinloch, Sabine ; Miro, Jose M. ; Kelleher, Anthony ; McClure, Myra ; Kaye, Steve ; Gabriel, Michelle ; Phillips, Rodney ; Weber, Jonathan ; Babiker, Abdel. / Short-course antiretroviral therapy in primary HIV infection. In: New England Journal of Medicine. 2013 ; Vol. 368, No. 3. pp. 207-217.
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AU - Fidler, Sarah

AU - Porter, Kholoud

AU - Ewings, Fiona

AU - Frater, John

AU - Ramjee, Gita

AU - Cooper, David

AU - Rees, Helen

AU - Fisher, Martin

AU - Schechter, Mauro

AU - Kaleebu, Pontiano

AU - Tambussi, Giuseppe

AU - Kinloch, Sabine

AU - Miro, Jose M.

AU - Kelleher, Anthony

AU - McClure, Myra

AU - Kaye, Steve

AU - Gabriel, Michelle

AU - Phillips, Rodney

AU - Weber, Jonathan

AU - Babiker, Abdel

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N2 - BACKGROUND: Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. METHODS: We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. RESULTS: A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P = 0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P = 0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P = 0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log10 copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. CONCLUSIONS: A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.)

AB - BACKGROUND: Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. METHODS: We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. RESULTS: A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P = 0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P = 0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P = 0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log10 copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. CONCLUSIONS: A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.)

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