CD4 Cell-Guided Scheduled Treatment Interruptions in HIV-infected Patients With Sustained Immunologic Response to HAART

Maggiolo, Franco; Airoldi, Monica; Callegaro, Annapaola; Martinelli, Canio; Dolara, Alberto; Bini, Teresa; Gregis, Giampietro; Quinzan, Giampaolo; Ripamonti, Diego; Ravasio, Veronica; Suter, Fredy

Disclosures

AIDS. 2009;23(7):799-807. 

In This Article

Abstract and Introduction

Abstract

Objective: To compare continuous HAART with a CD4 cell-driven scheduled treatment interruption (STI) strategy.
Methods: LOng Term Treatment Interruption study is a randomized, controlled, prospective trial. Patients with CD4 cell counts more than 700 cells/μl were eligible, and the immunologic threshold to resume HAART was 350 cells/μl. The primary end point was the development of an opportunistic disease, death from any cause or the occurrence of diseases, other than opportunistic, requiring hospital admission. Secondary end points were major adverse effects, virologic failures and therapeutic costs.
Results: Three hundred and twenty-nine patients were randomized 1: 1. Total follow-up was 1388 person-years (mean 4.2 years). Patients in the STI group stopped therapy for a total of 241 STI cycles, their mean off-therapy period was 65.3% of the follow-up. The primary end point occurred in 12.1% of patients on STI and in 11.6% of controls [odds ratio 1.05; 95% confidence interval 0.54-2.05]. A higher proportion of patients in the STI arm were diagnosed with pneumonia (P = 0.037), whereas clinical events influencing the cardiovascular risk of patients were significantly (P < 0.0001) more frequent among controls. Eight patients (4.8%) in the STI group and 11 (6.7%) controls developed viral resistance [odds ratio 0.79, 95% confidence interval 0.27-1.81]. The mean daily therapeutic cost was €20.29 for controls and dropped to €9.07 in the STI arm (P < 0.0001).
Conclusion: The two strategies may be considered clinically equivalent. CD4 cell-guided STIs seem a possible alternative for chronically infected individuals responding to HAART provided that CD4 cell decrements would be steadily maintained above a safe threshold.

Introduction

As the current regimens cannot eradicate HIV infection,[1] persons living with HIV are recommended to stay on life-long medication therapy. Pill fatigue, adverse effects and resistance continue to limit the effectiveness of HAART.[2,3] Scheduled treatment interruptions (STIs) have emerged as a possible strategy to ameliorate these problems.[4,5] Theoretically, STIs may decrease the cumulative time a patient is exposed to antiretroviral agents, thus improving quality of life, reducing the emergence of drug-related adverse effects and the chance of selecting for drug-resistant viruses, and may reduce therapeutic cost for patients or the healthcare system. However, the role of STIs within the modern management of HAART remains controversial.[6] Although several experiences have documented that CD4 cell-guided STIs may be virologically[7,8] and immunologically[9,10] safe among chronically infected patients responding to HAART, the benefit and risks of STIs can best be determined by long-term, controlled studies intended and powered not only to evaluate the risk of resistance or the immunologic response, but also to compare clinical outcomes including disease progression, AIDS, major toxicities and survival.[11]

We conducted a multicentre, controlled, prospective and randomized trial on a cohort of chronically HIV-infected individuals on effective HAART to address most of these open questions [LOng Term Treatment Interruption study (LOTTI)]. We chose to apply an individualized pulse therapy strategy, driven by CD4 cell count, and to compare it with conventional continuous HAART.

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