Background:  The Trivacan trial was launched in Abidjan in December 2002 to compare 2 different structured treatment interruption strategies with continuous HAART in chronically HIV-infected adults.

Methods:  Patients on suppressive HAART with CD4 >350/mm³ and plasma viral load <300 copies/mL were randomized to receive either:  continuous therapy (CT) (1 of 6 patients); or CD4-guided therapy (CGT) with introduction/interruption thresholds of 250/350 CD4/mm³ (2 of 6 patients); or 2-month-off/4-month-on therapy (2MO/4MOT) (3 of 6 patients). The endpoints were death and serious morbidity (any WHO stage 3 or 4 classifying event). An interim analysis was reviewed by an independent Data Safety Monitoring Board (DSMB) in October 2005. The DSMB recommended continuing the CT and 2MO/4MOT arms until trial termination, and stopping the CGT arm prematurely. We report only data from the CT and CGT arms. 

Results:  We randomized 110 patients in the CT and 216 in the CGT arms. The main baseline characteristics (all non-significantly different between arms) were:  77% women; 95% infected with HIV-1 alone; median age 34 years; median CD4 460/mm³; HAART regimen:  91% 2 NRTI + 1 NNRTI, 9% 2 NRTI + 1 PI. By October 31, 2005, overall median follow-up was 20 months, 4 patients were lost to follow-up, 5 patients were dead (incidence 0.6/100 person-years in CT arm, 1.2/100 person-years in the CGT arm, relative risk [RR] 0.48, 95%CI 0.01 to 4.91), and 60 patients had experienced 84 serious morbidity events (CT 6.7/100 person-years, CGT 15.2/100 person-years, RR 0.44, 95%CI 0.21 to 0.87). These clinical events were 42 oro-pharyngeal candidiasis (CT 2.3/100 person-years, CGT 6.4/100 person-years, RR 0.36, 95%CI 0.09 to 1.08), 24 invasive bacterial events (CT 0.6/100 person-years, CGT 6.7/100 person-years, RR 0.08, 95%CI 0.01 to 0.52), 16 tuberculosis (CT 2.3/100 person-years, CGT 3.6/100 person-years, RR 0.65, 95%CI 0.15 to 2.14), and 2 others. Of the 24 bacterial events, 14 occurred with documented bacteremia (all in the CGT arm) and 10 occurred without bacteremia but with hospital admission. In the 286 patients who reached month 12 after randomization (CT 96, CGT 190), the median (interquartile range [IQR]) month 12 CD4 count was 546/mm³ (IQR 452 to 645) in the CT arm and 333/mm³ (IQR 286 to 404) in the CGT arm.

Conclusions:  CGT led to a 2-fold higher serious morbidity rate than CT, mainly due to invasive bacterial diseases. Further structured treatment interruption trials assessing CGT strategies in sub-Saharan Africa should use higher CD4 thresholds for interruption/introduction. Whether a fixed treatment-interruption strategy is appropriate in Côte d’Ivoire requires further follow-up.