Goals and milestones during treatment of HIV-1 infection with antiretroviral therapy: a pathogenesis-based perspective.

Highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality related to infection with the human immunodeficiency virus-1 (HIV-1) through its ability to suppress viral replication and preserve and reconstitute specific immune responses in many infected individuals. However, the complete eradication of HIV-1 with current HAART regimens is not considered possible by most experts. Moreover, many current antivirals have metabolic complications and limiting side effects. Consequently, the treatment paradigm has shifted from 'hit hard and early' to delaying the initiation of therapy until later in the course of HIV-1-related disease, with corresponding modifications of consensus treatment guidelines. Factors that need to be considered in deciding when to initiate therapy and with what regimen include the patient's risk of disease progression, the possible adverse drug effects, the patient's ability to adhere to the prescribed therapy, and the need to preserve future therapeutic options. In this article, we discuss the issues surrounding the initiation of HAART, and describe the virologic and immunologic milestones that may be achieved with effective antiretroviral therapy.