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HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review

Bierman, Wouter FWa; van Agtmael, Michiel Aa; Nijhuis, Moniqueb; Danner, Sven Aa; Boucher, Charles ABb,c

doi: 10.1097/QAD.0b013e32831c54e5
Editorial Review

Objective: To assess the efficacy of ritonavir-boosted protease inhibitor monotherapy.

Design and methods: Systematic review of all protease inhibitor-monotherapy studies published in peer-reviewed journals or presented at conferences to date. Data of randomized controlled trials were pooled to yield common odds ratios.

Results: Twenty-two protease inhibitor-monotherapy studies were identified. In the intent-to-treat analysis, 395 out of 582 (67.9%) patients had undetectable HIV-RNA at the end of follow-up. In the six randomized controlled trials (all lopinavir/ritonavir monotherapy), the risk of therapy failure was greater on monotherapy: 121 out of 364 (33.2%) patients on monotherapy against 64 out of 280 (22.9%) patients on HAART [pooled odds ratio 1.48 (95% confidence interval 1.02–2.13, P = 0.037)]. Regarding patients with successfully resuppressed HIV-RNA upon (re-)introducing nucleoside reverse transcriptase inhibitors (NRTIs) as nonfailures, the risk of therapy failure was comparable: 98 out of 364 (26.9%) against 64 out of 280 (22.9%) patients [odds ratio 1.05 (95% confidence interval 0.72–1.53, P = 0.81)].

Conclusion: The overall efficacy of ritonavir-boosted protease inhibitor monotherapy is inferior to HAART. The efficacy improves in patients started on monotherapy after suppressed HIV-RNA for at least 6 months. Ten percent of patients have viral rebound with HIV-RNA levels between 50 and 500 copies/ml. Possible explanations are lack of HIV suppression in particular cells or compartments, alternative resistance mechanisms, and nonadherence. Once proven that reintroduction of NRTIs, in patients with loss of viral suppression, is safe and effective, a broader use of simplification of HAART to protease inhibitor monotherapy might be justified. This review supports that the majority of patients with prolonged viral suppression on HAART can successfully be treated with protease inhibitor monotherapy. Arguments for this strategy are NRTI/NNRTI side effects, NRTI/NNRTI resistance, and costs.

aDepartment of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

bDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands

cDepartment of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.

Received 5 June, 2008

Revised 6 August, 2008

Accepted 8 August, 2008

Correspondence to Dr Wouter Bierman, MD, Department of Internal Medicine, VU University Medical Center, Secretariaat Inwendige Geneeskunde, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Tel: +31 20 44 44 444; fax: +31 20 44 44 313; e-mail: w.bierman@vumc.nl

© 2009 Lippincott Williams & Wilkins, Inc.