Abstract: 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. The strategy of switching to triple nucleoside regimens shows weak evidence of lower incidence of side effects and a higher incidence of virologic failure in the 3NRTI group compared to controls. Simplification with 3NRTI holds the advantages of preserving other classes of antiretroviral drugs, to lower blood lipids, and to be cost effective and simple to administer.Thus, simplification with triple nucleoside regimens AZT + 3TC + ABC should be still considered for individuals who are unable to tolerate or have contraindications to NNRTI or PI based regimens. Additional data are needed on longer-term efficacy of triple NRTI regimens, particularly on the development of antiretroviral resistance. Though studies in the current review were conducted between 2001 and 2010, the large majority of patients from studies analysed received old PI regimens (e.g., indinavir, ritonavir, nelfinavir, saquinavir) not longer recommended by International Guidelines. Since current guidelines recommend new "lipid -friendly" PI, future studies should compare regimens containing these news PIs to triple NRTI regimens. More realistically, however, there are opportunities to examine these issues in existing cohorts.

Plain-language summary: We have reviewed clinical trials evaluating the efficacy and safety of abacavir-containing triple nucleoside combination as a simplification therapy in HIV-infected adult patients treated with a Protease-Inhibitor (PI)-containing regimen and  with undetectable viral load. Patients on a PI-containing regimen had three possibilities: continue the PI regimen or switch to a simplification maintenance regimen with triple nucleoside combination (abacavir-zidovudine-lamivudine) or with non-nucleoside (efavirenz or nevirapine) containing regimens. The review included 8 RCTs and 1675 HIV infected patients. Simplification with triple nucleoside regimen showed an overall failure rate comparable to that of  continuing  PI regimen or  to simplification with non-nucleoside regimens. Rates of failure due to adverse events with triple nucleoside combinations were lower compared to controls, but the difference was not statistically significant. By contrast, rates of virologic failures   were more frequent with  triple nucleoside combination that with PI or NNRTI, but in both the comparisons the differences were  not statistically significant. Simplification with abacavir had a favourable and significant impact on lipid metabolism compared to control group. Simplification with triple nucleoside regimens should be still considered for individuals who are unable to tolerate or have contraindications to NNRTI or PI based regimens