Hemophiliacs With Nonprogressive Human Immunodeficiency Virus Disease

In a study investigating plasma viremia in human immunodeficiency virus (HIV)-infected hemophiliacs with characteristics of long-term nonprogressors (LTNPs), Jimenez-Yuste et al describe individuals with a virological status similar to that reported by us,1-1 although with two notable exceptions. In our original studies, we have indicated an arbitrary cut-off value of about 10,000 copies of HIV RNA/mL of plasma below which all LTNPs hemophiliacs fit, whereas almost all control infected hemophiliacs with progressive disease had viral load levels above this value.1-1 Of interest, the control hemophilic progressors of Jimenez-Yuste et al show a mean value of plasma viremia very similar to what reported by us (271,333 v 284,521 HIV RNA copies/mL, respectively), despite the broad range shown by individual patients. In contrast, a higher level of viremia appears to characterize their LTNP hemophiliacs compared with ours (10,016 v 2,465 HIV RNA copies/mL of plasma, respectively). On this basis, the authors question the validity of the “10,000 copies threshold” concept, and, more importantly, point out that viremia levels in two of their patients largely exceed this value. Plasma viremia levels from an 18-month follow-up of our cohort of hemophilic LTNPs are shown in Table 1-1. These results suggest two important considerations. First, the possibility that different levels of viremia are the consequence of different methodologies implied in the studies appears of not particular relevance, particularly at low levels of viremia. Second, it is worthy of note that although 5 of 7 of our LTNPs remain essentially stable in terms of viremia (likely reflecting a well-controlled HIV infection), patient no. 3 has “crossed” the 10,000 copies threshold, and patient no. 2 is very close to it, making our small cohort today more similar to that reported here by Jimenez-Yuste et al. However, it should be noted that our patient no. 3 was already characterized by the highest viremia level at the time of the original study (Table 1-1). We agree with Jimenez-Yuste et al that larger studies on LTNP are warranted, but we also believe that these highly selected individuals, reaching in some cases 13 or more years since infection, and in good healthy conditions except for beiing hemophiliacs, are important biological exceptions in the natural history of HIV disease. Arbitrary thresholds, such as that of 10,000 copies, should simply be viewed as tools to study larger populations of individuals, whereas, at the same time, intra- and inter-assay variabilities should not be forgotten. Whether evolution of HIV disease, or, hopefully, the lack of it, can reliably be monitored by plasma viremia even in LTNPs remains a working hypothesis that only time will confirm or invalidate.