Our study reveals that NFV is a safe drug with a good profile and active to achieve an adequate response in HIV-1 infected children. NFV, like other PI, is highly active in vitro, therefore its activity in vivo is limited by their rapid clearance . Pharmacologic enhancement of PI with low doses of ritonavir (RTV) has been shown to increase drug concentrations . The combination of lopinavir (LPV) and RTV, has been widely used on paediatric patients and it has demonstrated a great activity, even higher as those reported with NFV . Nevertheless, LPV/RTV was not approved for administration to paediatric patients when our study was started . Moreover, the lipid abnormalities and insulin resistance reported in adults with LPV/RTV with an unknown effect on children [13, 14], the availability of a palatable form of NFV and the report of higher cross-resistance when LPV/RTV is used in a first line of HAART, has lead to an extensive use of NFV in paediatric age .
We recruited 42 infants who were not naïve to antiretroviral drugs. Nevertheless, NFV showed high efficacy in increasing the CD4+ cell count and early decreasing of VL among the three years of follow-up. Our results are similar to other studies which evaluate NFV efficacy among children [4, 16].
The presence of higher virologic failures at the end of our study, 71.4% compared with data published with adults, have been shown in previous analysis because children have higher VL and require longer times to achieve an uVL . Furthermore, our study recruit a high number of children older than 3 years, 74%, who have been taken ART for long periods of time and whose rates of virologic failure were higher that those reported in infant under 3 years, (77% vs. 56%). Besides, regarding to the unpredictability plasma concentrations of NFV that have been reported , the lack of therapeutic drug monitoring (TDM) measurement and analysis in a normal cohort (not in clinical trial) could have reduced the effectiveness in our study.
During the three years, 45% change the line of HAART and 38% interrupt NFV. These patients have similar characteristics at baseline so the use of a resistance test may have allowed selecting the most appropriate NRTI for each patient. Moreover, at baseline only 1/3 of children included 2 new NRTI in HAART line and 1/3 did not take any new NRTI. High virologic failure at the end of our study is probably due to previous resistance mutations to NRTI. Besides, new NNRTI or PI were added as second HAART line and some patients changed NRTI during the follow-up. However, the global tendency of VL was not improved which could be explained by the appearance of new resistance mutations to NRTI or cross resistance to PI. It is probable that if a resistance assay would have been used to guide changes of ART, virological response would have been higher.
Our study reveals that NFV is safe because only four patients experienced side effects. These results are considerably minor than other studies that reveal gastrointestinal side effects related to the use of NFV in 18% patients . On each follow-up visit only 40% achieve uVL. However, 90% have a decreased in VL >1 log10 and 70% have an uVL during the three years follow-up. Only VL at baseline was an important factor to predict VL control during the follow-up, as others studies have also shown .