The other hypothesis that could explain our results is a similar net balance between neuro-protection and neurotoxicity in patients treated with triple therapy or protease JW 74 inhibitor monotherapy. In vitro experiments have shown that antiretroviral drugs at concentrations achieved in the cerebrospinal fluid can produce neural damage. Two clinical studies have also suggested a possible neurotoxic effect of ART. In ACTG 5170 neuropsychological scores improved after ART interruption. In ACTG 736 ART regimens with higher CPE score were associated with poorer neurocognitive performance. It is possible than in patients receiving protease inhibitor monotherapy a possible lower neuro-penetrance could be compensated with lower neurotoxicity. Our results do not contradict prior reports of other types of neurological diseases in patients receiving protease inhibitor monotherapy. While our study is focused on neurocognitive impairment, these reports described patients with neurological symptoms such as meningitis associated to cerebrospinal fluid viral escape. Reports are heterogeneous because they have included patients with and without adequate plasma virological suppression. Neurological disease and cerebrospinal fluid viral escape has also been communicated in patients receiving triple drug ART. At present it is unclear if patients exposed to protease inhibitor monotherapy have a higher risk of cerebrospinal fluid virological escape and neurological disease. In the MONET clinical trial after three years of follow-up drug-related neuropsychiatric adverse events were infrequent for darunavir/ritonavir, either used as monotherapy or triple therapy. Our study has significant limitations. We cannot rule out the possibility of a beta error since we had only a 38% power to detect differences in prevalence of neurocognitive Irsogladine maleate impairment similar to the ones found between triple therapy and L-MT. However, in light our results, it is highly unlikely that the undetected effect favours the group on triple therapy. Besides, the upper limit of the 95% CI for the prevalence of neurocognitive impairment for patients who received protease inhibitor monotherapy for more than two years 232.3%- is consistent with the prevalence of neurocognitive impairment in suppressed patients receiving triple therapy. Another limitation of a cross-sectional study like ours is prescription bias. Protease inhibitor monotherapy is an option only for patients who have maintained HIV suppression for at least 6 months, without previous virological failure while on a protease inhibitor based regimen and preferably without low CD4 nadirs. It is logical that due to these restrictions patients receiving protease inhibitor monotherapy had slightly different characteristics than patients receiving triple therapy. We believe a systematic bias in favour of using monotherapy in patients with a lower risk of neurocognitive impairment, is unlikely. Differences between monotherapy and triple therapy groups had limited clinical relevance.