When to Start Therapy

    Royal Free Centre for HIV Medicine and Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, United Kingdom

    Highly active antiretroviral therapy (HAART) appears to significantly reduce the risk of clinical AIDS and death over the course of at least 35 years of follow-up in patients with high CD4 cell counts (e.g., >350 cells/mm3), although the absolute reduction in risk is not as great as it is in patients with lower CD4 cell counts [1, 2]. The data in the interesting paper by Wang et al. [3] on mortality in injection drug users (IDUs) are consistent with this. Indeed, Wang et al. showed that mortality in HIV-seropositive patients who began HAART when they had CD4 cell counts >350 cells/mm3 may be as low as that in HIV-seronegative IDUs. We would conclude that, if one is concerned only with this time span (and these outcomes), then the immediate initiation of HAART is preferable to deferring therapy, even in patients with high CD4 cell counts. However, most patients justifiably have a much longer-term perspective than that. Because some of the key benefits of deferring HAART can, by definition, only be realized during the longer term, follow-up times of at least 10 years are probably needed before it is possible to ascertain whether these benefits start to outweigh the clear early disadvantages of deferral. This is, of course, if we can also address the other issues that we all face in performing such analysesrecruiting sufficient numbers of patients and having no important residual biases (due to confounding, informative censoring caused by loss to follow-up, or other sources). We therefore feel that Wang et al.'s conclusion, which suggests that HAART should be initiated when patients have CD4 cell counts >350 cells/mm3, should be qualified.

    References

    1.  Phillips AN, Lepri AC, Lampe F, et al. When should antiretroviral therapy be started for HIV infection Interpreting the evidence from observational studies. AIDS 2003; 17:18639. First citation in article

    2.  Egger M, May M, Chene G, et al. Prognosis of HIV-1infected patients starting HAART: a collaborative analysis of prospective studies. Lancet 2002; 360:11929. First citation in article

    3.  Wang C, Vlahov D, Galai N, et al. Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: implications for when to initiate therapy. J Infect Dis 2004; 190:104654. First citation in article