Maximizing the Effectiveness of Highly Active Antiretroviral Therapy: Is There a Role for Quadruple Regimens?*

Although many highly active antiretroviral therapy (HAART) regimens using 3 drugs have demonstrated potent and durable antiretroviral effects, cohort studies have shown that treatment failure occurs in about 30% to 50% of patients. This failure rate prompts a closer look into the causes of treatment failure and how to modify or overcome these causes with new and more effective therapeutic regimens. Adherence to therapy may be the single most important factor affecting treatment outcomes with HAART. Factors affecting adherence include side effects of therapy, regimen complexity, total number of pills per day, pill size, food restrictions, water requirements, and dosing frequency. To improve adherence to HAART, dosing regimens must be simplified by reducing tablet load, removing food restrictions, and reducing dosing frequency. However, increased regimen convenience to achieve maximal adherence must be balanced with antiretroviral potency to achieve the lowest possible nadir. With a larger proportion of patients now beginning therapy with high viral loads and low CD4 cell counts, it is likely that many may not reach nadir on standard HAART regimens with 3 drugs. Therefore, maximized HAART regimens and 4drug (quadruple) regimens have been suggested and are being investigated. When given as initial HAART, quadruple regimens have shown promising preliminary results in recently completed studies and in ongoing comparative studies. (Advanced Studies in Medicine. 2002;2(23):827-831)