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doi: 10.1097/QAD.0b013e3282f3054f

Stopping antiretroviral therapy: role for therapeutic drug monitoring

Tommasi, Chiarab; Nicastri, Emanuelea; Corpolongo, Angelaa; Ivanovic, Jelenaa; Notari, Stefaniaa; Ascenzi, Paoloa; Andreoni, Massimob; Narciso, Pasqualea

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aNational Institute for Infectious Disease, IRCCS ‘Lazzaro Spallanzani’, Rome, Italy

bInfectious Disease Clinic, Department of Public Health, University ‘Tor Vergata’, Rome, Italy.

Received 24 September, 2007

Accepted 5 October, 2007

Correspondence and requests for reprints to Chiara Tommasi, Infectious Disease Clinic, Department of Public Health, University ‘Tor Vergata’, Via Montpellier 1, 00100 Rome, Italy. Tel: +39 06 55170420; fax: +39 06 55170407; e-mail:

In a recent paper, Taylor et al. [1] analysed different strategies for stopping antiretroviral therapy. The authors considered that, when drugs with different half-life were stopped simultaneously, the patient remains in a ‘functional monotherapy’, with longer half-life drugs still being active and a high probability of resistance emerging.

We experienced a CD4-guided treatment interruption in patients with a sustained viro-immunological response to antiretroviral therapy (persistently CD4 > 500/mmc and HIV-RNA < 50 cp/ml) after 24 months of highly active antiretroviral therapy (HAART) and no previous AIDS-defining illness. The criteria for restart therapy included CD4 cell counts ≤ 350/mmc, plasma HIV-1 RNA levels > 5.30 log10 copies/ml, the voluntary decision of the participant, and the development of an AIDS-defining illness or any acute severe clinical event during the study.

Among 62 recruited patients, we present data for nine Caucasian patients treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART who underwent therapeutic drug monitoring (TDM) at treatment interruption and weekly for 1 month. The ratio between the patient's drug level and the low normal reference value [2] was calculated and considered as the TDM ratio. As suggested by Taylor et al. [1], in attempting to overcome the potential for resistance development, we used a ‘staggered stop’ strategy by discontinuing longer half-life drugs, such as efavirenz and nevirapine, 2 weeks before the backbone with nucleoside reverse transcriptase inhibitors (NRTI). The genotypic assay was performed before starting any antiretroviral treatment and during treatment interruption. Data on CD4 cell count and HIV-RNA after 14 days, 30 days and monthly during treatment interruption were analyzed with SPSS 13.0 for Windows (SPSS Inc., Chicago, Illinois, USA).

The nine Caucasian HIV-infected patients included in the study had a median age of 41 years (interquartile range = 36–57 years) and seven patients (78%) were male. The median value of CD4 cell count at nadir was 325/mmc (interquartile range = 275–393/mmc) and, at treatment interruption, 802/mmc (interquartile range = 709–825/mmc). At day 14 after treatment interruption, the median CD4 cell count was 724/mmc (interquartile range = 537–849/mmc), with a median slope of 59 cells/mmc (interquartile range = –279 to 46 cells/mmc) and all but three patients had a still undetectable viral load.

At treatment interruption, the median NNRTI TDM ratio was 2.41 (interquartile range = 0.83–2.57) and, in three out of nine cases, the concentration was under the low reference value. At day 7 after treatment interruption, the median TDM ratio for NNRTI was 0.36 (interquartile range = 0.18–0.59), at day 14, the median ratio was 0.05 (IQ range 0.02–0.09) and, at day 21 after treatment interruption, NNRTIs were no longer detectable (Fig. 1).

Fig. 1
Fig. 1
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The patients remained in treatment interruption for a median of 90 days (interquartile range = 60–254 days). At therapy resumption, the median CD4 cells count was 330/mmc (interquartile range = 294–516/mmc). No new NNRTI- or NRTI- related mutations were detected during the treatment interruption period and all but one patient restarted the previous NNRTI-based regimen. All cases attained undetectable values of plasma HIV-RNA without virological rebound at follow-up.

In conclusion, the proposed staggered stopping policy is likely to be a feasible tool for phisicians and a valuable strategy for patients in terms of the lack of adverse events and the acquisition of new drug-related mutations.

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1. Taylor S, Boffito M, Khoo S, Smit E, Back D. Stopping antiretroviral therapy. AIDS 2007; 21:1673–1682.

2. la Porte CJL, Back DJ, Blashke T, Boucher CAB, Fletcher CV, Flexner C, et al. Update guideline to perform therapeutic drug monitoring for antiretroviral agents. Rev Antivir Ther 2006; 3:4–14.

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Journal of Medical Virology
Prognostic Factors of Long-Term CD4+Count-Guided Interruption of Antiretroviral Treatment
Sarmati, L; Andreoni, C; Nicastri, E; Tommasi, C; Buonomini, A; D'Ettorre, G; Corpolongo, A; Dori, L; Montano, M; Volpi, A; Narciso, P; Vullo, V; Andreoni, M
Journal of Medical Virology, 81(3): 481-487.
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© 2008 Lippincott Williams & Wilkins, Inc.


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