Background:  Early mortality data from the Children with HIV Early ART (CHER) trial comparing deferred to early ART started between 6 and 12 weeks of age was recently released. We now report on Bacille-Calmette-Guerin (BCG) -related complications in this cohort and in a comparator group of HIV-negative children recruited for a companion study(CIPRA–SA 004). BCG is given routinely at birth to all neonates in Africa, but there are few prospective data on BCG complications. Reports of lethal complications related to BCG vaccine given at birth to HIV-infected infants led to the World Health Organization (WHO) revising its recommendations regarding BCG vaccination of HIV-infected children. Additionally, BCG-adenitis related to immune reconstitution syndrome is emerging as an important issue.

Methods:  We randomized 292 HIV-infected infants between 6 and 12 weeks of age to immediate ART and 125 to deferred ART (to be initiated on CD4 or clinical criteria). HIV-negative children born to HIV-infected (n = 125) and HIV-uninfected mothers (n = 125) were a control group for a vaccine trial. All children received BCG vaccination at birth. Signs of local reactogenicity to BCG and other clinical events were documented from randomization.

Results:  The prevalence of regional BCG-adenitis among HIV-infected infants was 7.9% (5.5 to 10.9) (33 of 417); 13 in the deferred arm (10.4%) and 20 (6.9%) in the Early ART Arm (odds ratio 1.6, 0.8 to 3.3; p = 0.22). No HIV-negative children had local BCG-adenitis. Of the 33 instances of BCG-related regional adenitis, 31 (93.9%) occurred following initiation of HAART, suggesting IRIS; 2 patients in the deferred arm had pre-existing adenitis. Development of IRIS-related BCG-adenitis did not differ between the early-HAART (20 [6.8%] of 292; p = 0.48) vs the deferred HAART (11 [8.8%] of 125) groups. Of 33 cases with BCG-adenitis, 3 died, 2 of which were in the deferred arm and 1 in the early ART group. One (in the deferred arm) was considered related to BCG disease. Infants in the deferred arm received more concomitant therapy than in the early ART group (7 of 13 patients vs 4 of 20 for anti-mycobacterial treatment). Of 8 given prednisone, 7 were in the deferred arm (53.9%) and 1 in the early ART group (0.5%).

The percentage of local BCG reactogenicity to BCG was similar (>50%) regardless of HIV status.

Conclusions:  The incidence of IRIS-related BCG-adenitis was similar irrespective of timing of ART. Course of illness appeared more severe in children on delayed therapy. The appropriate treatment of children with IRIS-related BCG-adenitis remains to be confirmed.