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Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion—Reply

Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to... In reply Hocqueloux et al propose that longer duration of combined antiretroviral therapy (cART) in primary human immunodeficiency virus (HIV) infection (PHI) is associated with a higher probability of creating posttreatment controllers (PTCs). They cite as evidence the superior proportion of PTCs in their study compared with ours (15.6% vs 5.5%), as well as a number of studies that would support their hypothesis.1-5 While longer duration of cART administered during PHI may lead to a higher proportion of individuals controlling viral replication on its withdrawal, a hypothesis not supported by their own study or the ANRS (Agence Nationale de Recherche sur le Sida) CO6 PRIMO study by Goujard et al,3 studies differ by a number of factors other than treatment duration. Therefore, inference about the effect of cART duration from raw figures derived from published studies is inappropriate. In any case, it is erroneous to state that there were no PTCs in the SPARTAC (Short Pulse Anti Retroviral Therapy at HIV Seroconversion) study, which could not be deduced from the citation provided.5 In the study by Hocqueloux et al,1 the time at risk following treatment discontinuation was conditioned on not resuming cART within 24 months of discontinuation. In our study no such condition was required, since all individuals who had interrupted cART (and were suppressed at the time) contributed to the risk set until they experienced an event (viral rebound) or their follow-up was censored. The comparative figure from our study would be 8.5% (11 of 130 who did not reinitiate cART within 24 months of discontinuation). Finally, the denominator (25 629) used to derive the 1% from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe) who were treated at the time of PHI and subsequently stopped treatment is inaccurate and results in underestimating that proportion for our study. The appropriate denominator is of individuals with an HIV test interval less than 3 months, with at least 3 months of follow-up, at least 1 HIV RNA measurement, and who seroconverterted from 1996 onwards and would have, therefore, had the opportunity to have been treated with cART. Of 4010 such individuals in CASCADE, 259 (6.5%) interrupted cART. In conclusion, while the original study by Hocqueloux et al highlighted the existence of PTC, the key question is whether early treatment during PHI can help establish posttreatment control. Back to top Article Information Correspondence: Dr Porter, MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, United Kingdom (kp@ctu.mrc.ac.uk). Conflict of Interest Disclosures: Dr Porter has received an honorarium from Tibotec. References 1. Hocqueloux L, Prazuck T, Avettand-Fenoel V, et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS. 2010;24(10):1598-160120549847PubMedGoogle ScholarCrossref 2. Lodi S, Meyer L, Kelleher AD, et al. Immunovirologic control 24 months after interruption of antiretroviral therapy initiated close to HIV seroconversion. Arch Intern Med. 2012;172(16):1252-125522826124PubMedGoogle ScholarCrossref 3. Goujard C, Girault I, Rouzioux C, et al; ANRS CO6 PRIMO Study Group. HIV-1 control after transient antiretroviral treatment initiated in primary infection: role of patient characteristics and effect of therapy. Antivir Ther. 2012;17(6):1001-100922865544PubMedGoogle ScholarCrossref 4. Steingrover R, Pogány K, Fernandez Garcia E, et al. HIV-1 viral rebound dynamics after a single treatment interruption depends on time of initiation of highly active antiretroviral therapy. AIDS. 2008;22(13):1583-158818670217PubMedGoogle ScholarCrossref 5. Hamlyn E, Ewings FM, Porter K, et al; INSIGHT SMART and SPARTAC Investigators. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection. PLoS One. 2012;7(8):e4375422952756PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Internal Medicine American Medical Association

Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion—Reply

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References (5)

Publisher
American Medical Association
Copyright
Copyright © 2013 American Medical Association. All Rights Reserved.
ISSN
2168-6106
eISSN
2168-6114
DOI
10.1001/jamainternmed.2013.2784
Publisher site
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Abstract

In reply Hocqueloux et al propose that longer duration of combined antiretroviral therapy (cART) in primary human immunodeficiency virus (HIV) infection (PHI) is associated with a higher probability of creating posttreatment controllers (PTCs). They cite as evidence the superior proportion of PTCs in their study compared with ours (15.6% vs 5.5%), as well as a number of studies that would support their hypothesis.1-5 While longer duration of cART administered during PHI may lead to a higher proportion of individuals controlling viral replication on its withdrawal, a hypothesis not supported by their own study or the ANRS (Agence Nationale de Recherche sur le Sida) CO6 PRIMO study by Goujard et al,3 studies differ by a number of factors other than treatment duration. Therefore, inference about the effect of cART duration from raw figures derived from published studies is inappropriate. In any case, it is erroneous to state that there were no PTCs in the SPARTAC (Short Pulse Anti Retroviral Therapy at HIV Seroconversion) study, which could not be deduced from the citation provided.5 In the study by Hocqueloux et al,1 the time at risk following treatment discontinuation was conditioned on not resuming cART within 24 months of discontinuation. In our study no such condition was required, since all individuals who had interrupted cART (and were suppressed at the time) contributed to the risk set until they experienced an event (viral rebound) or their follow-up was censored. The comparative figure from our study would be 8.5% (11 of 130 who did not reinitiate cART within 24 months of discontinuation). Finally, the denominator (25 629) used to derive the 1% from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe) who were treated at the time of PHI and subsequently stopped treatment is inaccurate and results in underestimating that proportion for our study. The appropriate denominator is of individuals with an HIV test interval less than 3 months, with at least 3 months of follow-up, at least 1 HIV RNA measurement, and who seroconverterted from 1996 onwards and would have, therefore, had the opportunity to have been treated with cART. Of 4010 such individuals in CASCADE, 259 (6.5%) interrupted cART. In conclusion, while the original study by Hocqueloux et al highlighted the existence of PTC, the key question is whether early treatment during PHI can help establish posttreatment control. Back to top Article Information Correspondence: Dr Porter, MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, United Kingdom (kp@ctu.mrc.ac.uk). Conflict of Interest Disclosures: Dr Porter has received an honorarium from Tibotec. References 1. Hocqueloux L, Prazuck T, Avettand-Fenoel V, et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS. 2010;24(10):1598-160120549847PubMedGoogle ScholarCrossref 2. Lodi S, Meyer L, Kelleher AD, et al. Immunovirologic control 24 months after interruption of antiretroviral therapy initiated close to HIV seroconversion. Arch Intern Med. 2012;172(16):1252-125522826124PubMedGoogle ScholarCrossref 3. Goujard C, Girault I, Rouzioux C, et al; ANRS CO6 PRIMO Study Group. HIV-1 control after transient antiretroviral treatment initiated in primary infection: role of patient characteristics and effect of therapy. Antivir Ther. 2012;17(6):1001-100922865544PubMedGoogle ScholarCrossref 4. Steingrover R, Pogány K, Fernandez Garcia E, et al. HIV-1 viral rebound dynamics after a single treatment interruption depends on time of initiation of highly active antiretroviral therapy. AIDS. 2008;22(13):1583-158818670217PubMedGoogle ScholarCrossref 5. Hamlyn E, Ewings FM, Porter K, et al; INSIGHT SMART and SPARTAC Investigators. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection. PLoS One. 2012;7(8):e4375422952756PubMedGoogle ScholarCrossref

Journal

JAMA Internal Medicine – American Medical Association

Published: Mar 25, 2013

Keywords: hiv seropositivity,anti-retroviral agents

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