Evaluation of parvovirus B19 infection in children with malignant or hematological disorders.

more fundamental question: what is the rationale for treating elite suppressors with cART in the first place? We know that many of these patients are probably infected with fully replication-competent human immunodeficiency virus (HIV)–1 isolates [2, 3]. Furthermore, a comparison of proviral and plasma HIV clones suggests that viral evolution has occurred in these patients, meaning that the virus has to be replicating at low levels [4]. Although the majority of elite suppressors maintain stable CD4 T cell counts, CD4 T cell depletion has been reported in some elite suppressors [5–8], all of whom have had marked levels of immune activation. Immune activation has been shown to be a better correlate of HIV progression than viremia in some studies [9, 10], and in fact, Kaposi sarcoma has been reported in an elite suppressor with relatively high levels of immune activation [7]. In our study, we showed that treatment of an elite suppressor with highly active antiretroviral therapy (HAART) resulted in a marked decline in immune activation even though there was not a significant increase in CD4 T cell count [8]. Thus, one could argue that treatment with HAART will inhibit the low-level viral replication that is probably responsible for the immune activation in elite suppressors. More patients will have to be studied before we can determine whether this strategy generally results in immune reconstitution, but how do we define success in cases in which CD4 T cell counts do not rebound? Elite suppressors have viral loads of !50 copies/mL at baseline, so using commercial viral load assays with cutoff values of 50 copies/mL will be of little help, and it is obviously challenging to monitor these largely asymptomatic patients for other signs of clinical improvement. The CD4 T cell count in our patient stabilized during HAART [8]; this probably should be the minimum criterion used in these cases. Finally, one could ask whether it makes sense to treat all elite suppressors with HAART. Studies have shown that, although these patients have higher levels of immune activation than uninfected subjects [6, 7], the majority maintain stable CD4 T cell counts for long periods of time [8, 11, 12]. Studies comparing large cohorts of elite suppressors and patients who are receiving HAART will be needed to determine whether subtle differences in morbidity and mortality exist; ultimately, this will guide the decision-making process. However, it should be noted that, although many elite suppressors have been clinically stable for 120 years without therapy, nobody has been taking HAART for that long; thus, the long-term consequences of this treatment remain unknown.