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A Review of HIV Monotherapy with Ritonavir-boosted Protease Inhibitors

There is increasing interest in the simplification of combination antiretroviral therapy in order to lower pill burden, improve convenience, and reduce the costs of HIV treatment.

In a review published in the December 24, 2008 online edition of AIDS, Dutch researchers evaluated the efficacy of ritonavir-boosted protease inhibitor (PI) monotherapy. Monotherapy regimens do not include nucleoside reverse transcriptase inhibitors (NRTIs) like traditional HAART.

The investigators systematically reviewed all protease inhibitor monotherapy studies published in peer-reviewed journals or presented at research meetings to date.

Results

• 22 protease inhibitor monotherapy studies were identified.
• In an intent-to-treat analysis, 395 out of 582 patients (67.9%) receiving monotherapy had undetectable HIV RNA at the end of follow-up.
• In the 6 randomized controlled trials -- all of lopinavir/ritonavir (Kaletra) monotherapy -- the risk of treatment failure was greater on monotherapy: 121 out of 364 patients (33.2%) on monotherapy versus 64 out of 280 (22.9%) on traditional HAART (P = 0.037).
• When counting patients who successfully re-suppressed HIV RNA after reintroducing NRTIs as non-failures, the risk of treatment failure was comparable: 98 out of 364 patients (26.9%) using monotherapy versus 64 out of 280 (22.9%) using traditional HAART (P = 0.81).

The study authors concluded that the overall efficacy of ritonavir-boosted protease inhibitor monotherapy is inferior to that of traditional HAART. They also wrote that efficacy improves in patients started on monotherapy after they achieve HIV RNA suppression for at least 6 months.

The review indicated that 10% of patients using monotherapy experience viral rebound with HIV RNA levels between 50 and 500 copies/mL. "Possible explanations," the authors wrote, "are lack of HIV suppression in particular cells or compartments, alternative resistance mechanisms, and non-adherence."

Once it is proven that reintroduction of NRTIs, in patients with loss of viral suppression, is safe and effective, they added, "a broader use of simplification of HAART to protease inhibitor monotherapy might be justified."

Finally, they concluded, "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."

Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands; Department of Virology, Erasmus Medical Center, Rotterdam, Netherlands.

1/13/09

Reference

WF Bierman, MA van Agtmael, M Nijhuis, and others. HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review. AIDS. December 24, 2008 [Epub ahead of print]. (Abstract).