Reported despite being informative of immune reconstitution and complementary to the
Reported despite being informative of immune reconstitution and complementary to the CD4 cell count [21]. The CD4 cell dynamics observed here are concordant with published data on treatment initiation during chronic HIV infection [22-26]. The overall immune response to treatment varies according to the CD4 cell count at cART initiation [22,25-27]. Patients with an initial count of 250?500 CD4 cells/mm3 will gain about 200 cells/mm3 during the first year of cART [27]. Reconstitution of the CD4 cell pool exhibits a biphasic pattern, with a rapid increase during the first 3 months, due to redistribution of memory cells from lymphoid tissue, followed by a substantially slower increase [22,28]. In the CASCADE collaboration, the slope of CD4 cell recovery during treatment started in CHI was similar to that observed here, with +0.95 CD4count/ month in the first 3 months, and +0.105CD4count/month thereafter [23]. It is widely agreed that interruption of long-term cART started during CHI is harmful. In the CASCADE collaboration and SMART trial, poorer immune reconstitution was observed after ART resumption than during first-line cART initiated during CHI [23,29]: two years after cART resumption the CD4 cell count had returned to the pre-interruption level in fewer than half of the patients [30]. The difference in CD4 cell recovery observed here between patients who resumed cART after transient treatment started during PHI and those who started PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26104484 cART during CHI might have resulted indirectly from drug resistance following cART interruption, yet no difference in the viral response was observed. Moreover, in the sensitivity analysis restricted to sustained viral responders, the CD4 count slope was still shallower in the cART resumption group. The detrimental consequences of discontinuing cART started during CHI have been explained in terms of increases in markers of inflammation, coagulation and immune activation, coinciding with the viral rebound after cART interruption [31,32]. A similar inflammation/activation phenomenon might also explain the results obtained here after interruption of transient cART initiated during PHI. We could also argue whether patients who initiated ART during primary HIV infection might have had a more “pro-inflammatory phenotype”, which caused lower long-term CD4 increases though the effect of pro-inflammatory cytokines, such as TNF. There is evidence that TNF might affect CD4 count after cART interruptions in CHI [32]. The levels of T cell activation PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28549975 and inflammatory cytokines (IL-1, eotaxin and IL-7) during PHI have been found to be strong independent predictors of the rate of spontaneous CD4 cell count decline in untreated patients, but there are no such data for patients who interrupt transient cART initiated during PHI [32-34]. In the ANRS Interprim trial, in which serial short interruptions were programmed after treatment initiation during PHI, a gradual decrease in the mean CD4 cell count and U0126 price percentage was observed over time, with no return to the mean values reached before the first interruption [20]. One limitation of our work, as in any observational study, is that the patients who interrupted cART after transient treatment started during PHI might have had different prognostic status from those who started cART during CHI. However, complementary analyses that took into account potentially unfavourable characteristics at HIV infection, as well as the duration and type of first-line cART regimen and the duratio.
