Challenges in the study of patients with HIV type 1 seroconversion.

In this issue of Clinical Infectious Diseases, Madec et al. [1] report that spontaneous and sustained clearance of HIV type 1 (henceforth, HIV) viremia (defined as repeated HIV RNA levels in plasma of !500 copies/mL) is not uncommon in persons recently infected with HIV. Undetectable viremia occurred in 4% and 6% of 426 individuals in the French SEROCO cohort within 1 and 2 years after infection, respectively , and was observed in ∼7% of these persons at 5 years after infection. Low-level viremia is recognized to be correlated with long-term nonprogressive HIV infection [2]. Thus, it is an important clinical end point for studies of interventions during acute-phase and early-phase HIV infection. Nevertheless, use of low-level viremia to interpret the impact of treatments in nonrandomized studies of patients with HIV seroconversion (i.e., HIV seroconverters) is problematic. Discrepancies in reported frequencies of undetectable viremia among HIV sero-converters highlight the difficulty of using such studies to interpret the results of treatment trials. Among an Amsterdam cohort of 123 HIV seroconverters, plasma HIV RNA level was !1000 copies/mL in 14% of untreated HIV seroconverters 1 year after seroconversion, but only 2% had virus loads !1000 copies/mL 5 years after seroconversion [3]. These data suggest a substantially higher incidence of baseline low-level viremia among HIV serocon-verters than that reported by Madec et al. [1] but a lower incidence of sustained low-level viremia 5 years after seroconversion. Long-term rates of undetectable viremia have also varied in studies of HAART-treated HIV seroconverters. Of 14 HIV seroconverters who were selected on the basis of intact HIV–specific lymphopro-liferative responses after having received HAART, 4 (29%) had episodes of viremia of !500 copies/mL during у1 structured treatment interruption (STI), and 1 (7%) had sustained plasma HIV RNA concentrations below that level a median of 5.3 years after infection [4], which is similar to the results reported by Madec et al. On the other hand, in 2 other small studies of HAART-treated HIV seroconverters who had received early antiretroviral therapy and, in some cases, HIV vaccination, sustained viremia of !500 copies/mL within the first 1.5 years of discontinuation of an-tiretroviral treatment did not occur [5, 6]. Discrepant prevalences of undetectable viremia during follow-up are likely to be, at least in part, due to differences in the study participants' characteristics. Although as many as 90% of HIV seroconverters experience some sort of clinical illness associated with primary HIV infection [7], most …