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Immunological Responses and Long-Term Treatment Interruption after Human Immunodeficiency Virus Type 1 (HIV-1) Lipopeptide Immunization of HIV-1-Infected Patients: the LIPTHERA Study

Gilles Pialoux,^1,5* Romina P. Quercia,¹ Hanne Gahery,² Nathalie Daniel,³ Laurence Slama,¹ Pierre-Marie Girard,⁴ Philippe Bonnard,¹ Willy Rozenbaum,^1,5,6 Véronique Schneider,¹ Dominique Salmon,³ and Jean-Gérard Guillet^2,

APHP, Tenon Hospital, Paris, France,¹ Cochin Institute, INSERM U567, Paris, France,² APHP, Cochin Hospital, Paris, France,³ APHP, Saint-Antoine Hospital, Paris, France,⁴ Université Pierre et Marie Curie, Paris, France,⁵ APHP, Saint-Louis Hospital, Paris, France⁶

Received 18 April 2007/ Returned for modification 2 September 2007/ Accepted 19 December 2007

We studied the time course of immunological and virological markers after highly active antiretroviral therapy (HAART) interruption in chronically human immunodeficiency virus type 1 (HIV-1)-infected patients immunized with an HIV lipopeptide preparation. In a prospective open pilot study, 24 HIV-1-infected HAART-treated patients with undetectable plasma viral loads (pVLs) and CD4⁺ T-cell counts above 350/mm³ were immunized at weeks 0, 3, and 6 with a candidate vaccine consisting of six HIV lipopeptides. At week 24, patients with pVLs of <1.7 log₁₀ copies/ml were invited to stop taking HAART. Antiretroviral therapy was resumed if the pVL rose above 4.47 log₁₀ copies/ml and/or if the CD4⁺ cell count fell below 250/mm³. Immunological and virologic parameters were studied before and after HAART interruption. The median baseline and nadir CD4⁺ cell counts were 482 (interquartile range [IQR], 195 to 826) and 313 (IQR, 1 to 481)/mm³, respectively. New specific CD8⁺ cell responses to HIV-1 epitopes were detected after immunization in 13 (57%) of 23 assessable patients. Twenty-one patients were evaluated 96 weeks after HAART interruption. The median time to pVL rebound was 4 weeks (IQR, 2 to 6), and the median peak pVL was 4.26 (IQR, 3 to 5) log₁₀ copies/ml. Thirteen of these 21 patients resumed HAART a median of 60 weeks after immunization (IQR, 9.2 to 68.4 weeks), when the median pVL was 4.8 (IQR, 2.9 to 5.7) log₁₀ copies/ml and the median CD4⁺ cell count was 551 (IQR, 156 to 778)/mm³. Eight patients were still off therapy at 96 weeks, with a median pVL of 4 (IQR, 1.7 to 4.6) log₁₀ copies/ml and a median CD4⁺ cell count of 412 (IQR, 299 to 832)/mm³. No clinical disease progression had occurred. Despite the lack of a control arm, these findings warrant a randomized study of therapeutic vaccination with HIV lipopeptides followed by long-term HAART interruption in AIDS-free chronically infected patients.

Published ahead of print on 9 January 2008.

In memoriam.