Transcript Antiretroviral Treatment Simplification to Ritonavir

Antiretroviral Treatment Simplification to Ritonavir-boosted Protease Inhibitor
Monotherapy: Systematic Review and Meta-analysis
Javier Ena, Francisco Pasquau, Rosa F. Ruiz-de-Apodaca
Hospital Marina Baixa. Alicante. Spain
Abstract (Updated)
Background: Ritonavir-boosted protease-inhibitor (PI)-monotherapies are an attractive
alternative to conventional therapy in order to avoid the potential mitochondrial toxicity
and lipoatrophy associated with NRTI drugs. We carried out a systematic review and
meta-analysis of clinical trials evaluating the effectiveness and safety of strategies
using induction with two NRTI and one PI/r and maintenance with one PI/r.
Methods: Literature review in electronic databases and proceedings and abstracts from
major Conferences in Infectious Diseases and HIV infection. Studies were included in
the analysis if 1) Patients were treated with Ritonavir-boosted protease-inhibitor (PI)monotherapy after achieving complete virological suppression with standard 3-drug
regimen, 2) Follow-up was at least 24 weeks and 3) Virological failure and
discontinuation rate was reported at the end of follow up. Analysis was carried out by
intention-to-treat (Missing=failure).
Results: We identified a total of 13 studies. In 9 single arm studies (3 ATV/R, 2 LPV/R
and 1 IDV/R) recruiting a total of 115 patients with follow-up from 24 to 48 wks, there
were 20 patients with virological failure in 73.59 patient-year follow-up (Failure rate
27.18 per 100 patient-years; 95% CI: 17.07 to 41.23). In 4 randomized clinical trials (4
LPV/R) recruiting a total of 462 patients with follow up from 48-96 wks, the failure rate
was 56 in 354 patient-years follow up in the intervention group vs. 27 out in 262 patientyears follow-up in the control group (Risk Difference 5.51 per 100 patients-year; 95%
CI: from -0.16 to 11.19; p= 0.06), with no heterogeneity among trials (I2=0%; p=0.54).
Discontinuation due to severe side effects were 1 out from 154 (0.65%) in the
intervention group vs. 4 out from 153 (2.61%) in the control group (Relative Risk: 0.49:
95% CI: 0.08-2.41; p=0.43), with no heterogeneity among trials (I2=0.4%; p=0.37)
Conclusion: Switching from triple drug therapy to ritonavir-boosted protease-inhibitor
monotherapies in patients who were virologically suppressed is less effective than
standard HAART.
Objectives
Methods
Results
Searching: MEDLINE, EMBASE, Conference Reports Index, Cochrane Controlled Trails
Register, Cochrane Database of Systematic Reviews. A search strategy was developed
with an aid of an expert librarian. In addition, a hand search was carried out to identify
unpublished information from the most important conferences on HIV and infectious
diseases.
Selection: Single-arm trials and randomized controlled trials. (Population: HIV-infected
patients with HIV RNA not detectable at study entry; Intervention: Treatment with
ritonavir-boosted single protease-inhibitor therapy, Principal outcome: virological failure
as it was defined in each study.
Data abstraction: process of data completed independently, in duplicate.
Quantitative data synthesis: Single arm studies principal measures of effect (failure rate
by 100 patient-years of follow-up with 95% confidence intervals) (OpenEpi calculator).
Analysis as intention to treat (missing=failure) and as per-protocol (virological
failure=failure). Randomized clinical trials principal measures of effect (Relative Risk
failure rate at end of follow-up) (RevMan 4.2).
Conclusions
Switching from triple drug therapy to ritonavir-boosted protease-inhibitor monotherapy in
patients who are virologically suppressed is less effective than standard HAART.
Results
To assess the effectiveness of ritonavir-boosted protease inhibitor monotherapy to
maintain virological suppression in patients who had HIV RNA below the detection
limit.
References
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Correspondence: [email protected]
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