A randomized, controlled, trial of short cycle intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda.

BACKGROUND: Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs. METHODS: A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count > or =125 cells/mm(3) and HIV RNA plasma levels <50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection. RESULTS: Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39). CONCLUSIONS: Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339456.

Evolution of drug resistance after virological failure of a first-line highly active antiretroviral therapy regimen in Uganda.

BACKGROUND: This study aimed to determine the extent of viral resistance over time among non-clade B HIV type-1-infected patients in Uganda who were maintained on first-line highly active antiretroviral therapy (HAART) following virological failure. METHODS: Genotyping was performed on 16 patients with virological failure who were enrolled in an open-label randomized clinical trial of short-cycle treatment interruption. RESULTS: All patients receiving efavirenz-containing HAART had > or =1 efavirenz resistance mutation develop during follow-up. The majority (13/15, 86%) developed lamivudine resistance during follow-up, but no thymidine analogue mutations (TAMs) developed during a median duration of virological failure of 325.5 days. CONCLUSIONS: Genotype resistance to both efavirenz and lamivudine developed early during the course of treatment after virological failure. TAMs did not emerge early despite moderate exposure time to thymidine analogues during virological failure.