Antiretroviral Therapy: Time To Think Strategically

• Anti-HIV agents
• Virus replication
• Human immunodeficiency virus infections
• Viremia
• Drug resistance, microbial

Highly active antiretroviral therapy (HAART), the use of combinations of antiretroviral drugs that can profoundly suppress HIV replication for prolonged periods, has substantially decreased AIDS-related morbidity and mortality in the United States and western Europe (1). However, the optimal use of antiretroviral drugs remains a rapidly evolving field and numerous obstacles need to be addressed. Many HAART regimens are associated with substantial toxicity, large pill burdens, and high cost. In addition, it has become clear that currently available HAART regimens cannot completely suppress HIV replication (2).

Guidelines for the optimal use of antiretroviral therapy have been issued by several panels of experts (3). Recommendations on the best time to initiate antiretroviral therapy are based on studies of the relation between surrogate markers of HIV disease progression and risk for clinical progression to AIDS (4). On the basis of these data, antiretroviral therapy is usually recommended for asymptomatic patients with CD4⁺ counts less than 500 cells/mm³ or plasma viral levels less than 10 000 HIV RNA copies/mL. Decisions about which antiretroviral agents to use in these circumstances and when to switch therapy are guided by published data and expert opinion. To keep pace with rapidly evolving concepts, the guidelines issued by the U.S. Department of Health and Human Services (DHHS) and the Henry J. Kaiser Family Foundation (3) are updated frequently on the World Wide Web (http://www.hivatis.org).

In this issue, Henry (5) argues for a …