Recent HIV-1 Infection: To Treat or Not to Treat, That Is the Question

Abstract

The first description of acute human immunodeficiency virus (HIV) infection as a mononucleosis-like syndrome was published in 1985 [1]. Since that time, it has become clear that recent viral infection may be accompanied by a variety of symptoms, at least partly related to the mode of acquisition [2], and may often be asymptomatic [3]. Despite this apparent lack of specificity of clinical presentation, it still remains possible to identify individuals who have acute/early HIV infection by educating healthcare providers and patients alike to consider this diagnosis in the context of a significant systemic illness in an individual with a recent risk exposure. Alternatively, a strategy of repeated testing for infection (using fourth-generation tests detecting the virus as well as the antibody response) in some groups may be employed. The main reason to develop such a strategy would be the availability of an intervention to change the natural history of the disease. An early controlled trial of a 6-month course of zidovudine monotherapy in primary HIV infection showed a clinical effect on minor opportunistic infections over a 15-month period, as well as significant increases in CD4 cell counts [4]. Interestingly, study recruitment was ended prematurely, at least in part because practitioners of the day believed that the correct course of action was to initiate treatment and were unwilling to randomize their patients to observation. In an accompanying editorial, Ho reasoned that the observed benefit related to a marked effect on viral dynamics at a time when viral turnover was at its peak [5]. He further proposed that when more effective treatment modalities were available, the benefit would be even greater. Over time, an immunologic benefit of intervention (the preservation of HIV-specific T-helper cells) was demonstrated to support the rationale for intervention [6]. Since then, enthusiasm for the systematic use of highly active antiviral therapy in this setting has waned, with the benefit of interrupted therapy expected to be modest and without long-term benefit [7]. The current Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in HIV-1–Infected Adults and Adolescents states that ‘‘The health care provider and the patient should be fully aware that the rationale for therapy for acute HIV infection is based on theoretical considerations, and the potential benefits should be weighed against the potential risks. For these reasons, treatment of acute HIV infection should be considered optional at this time’’ [8]. It is in this nebulous context that the important work of Hogan and colleagues is published in this issue of the Journal [9]. The Setpoint Study (ACTG A5217) was a randomized clinical trial in which patients who had been infected with HIV in the previous 6 months were assigned to receive a 36-week course of antiretroviral therapy (with tenofoviremtricitabine administered along with lopinavir-ritonavir) or observation. The principal end point was a lowering of the virologic set point at week 72 (thus comparing 36 weeks of therapy followed by 36 weeks of observation with 72 weeks of observation). The secondary end point was the time required to meet eligibility for therapy based on clinical, virologic, and/or immunologic criteria. As with the original trial of zidovudine monotherapy in this setting, the study was discontinued prematurely. The Data Safety Monitoring Board (DSMB) determined that study subjects who did not receive immediate treatment were progressing to require such treatment on clinical grounds at such a rate that an actual comparison of virologic set points between the 2 study groups would not be possible. Of the planned 150 participants, 130 had been enrolled before the closure of Received and accepted 26 September 2011. Correspondence: Brian Conway, MD, FRCPC, Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Downtown ID Clinic, 201-1200 Burrard St, Vancouver, BC V6Z 2C7, Canada (bconway@exchange.ubc.ca). The Journal of Infectious Diseases 2012;205:10–2 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com DOI: 10.1093/infdis/jir702