Although combination antiretroviral therapy (ART) has been successful in suppressing plasma HIV RNA levels in infected patients, it has not resulted in eradication of virus. Prolonged, continuous ART results in significant toxicities and difficulties adhering to drug regimens. In addition, the cost of antiretroviral drugs is prohibitive for many individuals and countries. Therefore, we have studied the virologic and immunologic effects of intermittent versus continuous ART in HIV-infected individuals in an attempt to reduce the total time an individual receives therapy while maintaining therapeutic efficacy. To test the need for and feasibility of strict adherence to a short-cycle intermittent ART regimen, we are currently conducting a randomized, controlled trial of short cycle (5 days on, 2 days off) intermittent therapy versus continuous ART in Kampala, Uganda (Protocol 02-I-N288, ?A Randomized, Controlled Trial of Short Cycle Intermittent versus Continuous HAART for the Treatment of Chronic HIV Infection in Uganda). The study originally included a 7/7 arm (7 days on, 7 days off) but was discontinued because several patients failed specific study criteria. Patients initially enrolled in the 7/7 arm were transferred to continuous therapy and are being monitored for the original duration of the study (73 weeks). To date, 152 patients have been enrolled; 34 in the 7/7 arm, 60 in the 5/2 arm and 58 in the continuous arm. The 5/2 and continuous arms have subscribed above the original 57 person limit due to the 1-to-1 replacement for individuals who had elevated plasma HIV RNA or low CD4+ T cell counts on day zero despite meeting criteria at screening. The study will be fully accrued with 2 more persons enrolled, one in each of the remaining arms. Twenty-seven patients have reached an endpoint in the 7/7 arm (reached week 72 per protocol or failed prior to week 73). Of these, there were 9 failures while receiving intermittent therapy; 5 patients had plasma HIV RNA levels > 50 c/ml at week 72 ? 4 of these had viral loads >50/<200 c/ml, while one patient had a viral load >200 c/ml at week 72. The total number of failures per protocol is 15. Twenty-five patients have reached an endpoint in the 5/2 arm (reached week 73 or failed prior to week 73). Two patients failed prior to week 73; 4 patients had a viral load of >50/<200 c/ml at week 73; no patient had a viral load > 200 c/ml at week 73. The total number of failures per protocol is 6. In summary, short cycle intermittent ART may be an important option for the treatment of HIV infection to reduce cost and, possibly, toxicity while potentially enhancing adherence. If safety and efficacy of short-cycle intermittent therapy is ultimately demonstrated in clinical settings, it might prove to be an important strategy to expand therapy in resource-limited settings.
