Our findings indicate that the difference in hospitalization risk between virological responders and nonresponders starts to occur at 45 days after HAART initiation, may then plateau after 90 days, and is independent of having a large Dabrafenib mw CD4 increase after HAART initiation. The decreases in hospitalizations
as a result specifically of ADIs and non-ADI infections among virological responders indicate that much of the clinical benefit of immune reconstitution may occur between 45 and 90 days after HAART initiation. Furthermore, this benefit may be independent of having a large increase in absolute CD4 cell count after HAART initiation. The initial redistribution of mature CD4 cells from lymphoid tissue to peripheral blood tapers within approximately Afatinib the same 45- to 90-day time period [28–30]. Clinical benefit may thus appear once an effective repertoire of mature CD4 cells reaches the periphery. Although the number of events was small, the
possibility of decreased rates of ADI admissions for nonresponders after 90 days of HAART suggests a possible protective effect even in the absence of a virological response at 6 months. Studies have indicated possible increases in liver-related and cardiovascular illnesses since the advent of HAART [4–6,31,32]. There have been conflicting results regarding whether cardiovascular risk occurs within a few months or after years of HAART exposure [31,32]. Among virological responders in our study, there was no evidence of increased hepatic or cardiovascular hospitalization rates during the first year after HAART initiation. There was a suggestion that nonresponders (who may have had a brief virological response which then terminated prior to 6 months) had an increased risk of gastrointestinal/liver and cardiovascular illnesses, although numbers of events are too small to be conclusive. IRIS led to >13% of all admissions among responders in the first 45 days. Making a diagnosis of IRIS is often complicated and costly as very new infections must be considered and ruled out. Previous studies have shown that 20–25% of persons starting
HAART will experience an IRIS event, not all of which lead to hospitalization [33,34]. Using the cases within this study, we have previously analysed predictors of IRIS and found boosted PIs, CD4 nadir <100 cells/μL, and HIV-1 RNA decrease >2.5 log10 copies/mL following initiation to be independently associated with IRIS . Calendar era made no appreciable difference to risk of hospitalization during the year following HAART initiation in our analysis. Despite US public health efforts, persons in recent years have enrolled for HIV care at similarly advanced levels of immune compromise as in 1998 and earlier [18,35]. Our results indicate that, until more patients initiate HAART at higher CD4 cell counts, there will continue to be a substantial hospitalization burden in the several weeks after HAART initiation.