Abacavir-based triple nucleoside regimens for maintenance therapy in patients with HIV.Cochrane Database Syst Rev. 2013 Jun 05CD
Regimen simplification can be defined as a change in established effective therapy to reduce pill burden and dosing frequency, to enhance tolerability, or to decrease specific food and fluid requirements. Many patients on suppressive antiretroviral therapy may be considered candidates for a simplification strategy and, among them, those who have achieved virologic suppression. Several clinical trials have evaluated the efficacy of triple nucleoside combination as a simplification therapy in patients who achieved virologic suppression
The aim of this review is to combine randomised, controlled trials to examine whether in patients with undetectable viraemia on a Protease inhibitor (PI) based regimen simplification treatment with abacavir (ABC)-based triple-nucleoside combinations has similar rates of efficacy and tolerability compared with a PI regimen or simplification with a NNRTIs (efavirenz-EFV- or nevirapine-NVP) containing regimen. Studies were included if they had at least two of the three interventions, including one 3NRTI arm.
Electronic databases and conference proceedings were searched (1996-2012) with relevant search terms without limits to language.
Randomised controlled trials (RCTs) only are included in this review. Patients population is represented by HIV-infected adult patients treated with a PI-containing regimen (PI or boosted PI), with undetectable viral load. Patients on a PI-containing regimen had three possibilities: continue the PI regimen or switch to a simplification maintenance regimen, including switch to a NNRTI (EFV or NVP) containing regimen, or switch to a triple-NRTI regimen (ABC-zidovudine-lamivudine)
DATA COLLECTION AND ANALYSIS
The primary outcomes were: proportion of patients discontinuing or switching antiretroviral therapy due to virologic failure or to adverse events; death (all cause) and AIDS defining illness; occurrence of myocardial infarction and cardiovascular disease. Secondary outcomes were: proportion of patients maintaining an undetectable viral load (e.g. HIV-RNA <50 or <400 copies/mm(3)); change in mean CD4+ cell count; occurrence of lipodystrophy. We applied Cochrane Collaboration tools to assess each individual study for risk for bias.
We included eight RCT, for a total of 1,610 patients. All the studies included HIV-1 infected patients virologically suppressed after a successful treatment with PI containing ART. Articles included in the analysis were published between 2001 and 2010, and could be classified as low risk of bias trials in most of the domains considered. Overall, there was no significant difference between the participants on triple nucleoside combination and controls, either PI-based or NNRTI based in terms of overall failures, death and AIDS related events, and rates of patients with viral load below the detectability cut-off. For the outcomes discontinuation for adverse events and virologic failures, the RRs were not significant , albeit being not far from the alpha level of 0.05, thus suggesting a weak evidence of lower incidence of side effects and an higher incidence of virologic failure in the 3NRTI group compared to controls . Change in lipids and in CD4 cells from baselines were reported in 7 studies, but inconsistency in reporting these data did not allow quantitative analysis. However, all agreed that simplification with ABC had a favourable and significant impact on lipid metabolism compared to control group. An increase in CD4 cells count from baseline was evident in all analysed studies, without significant differences between ABC and controls in individual studies.