Complications with BCG vaccination in HIV-positive and negative infants: CHER Study

Polly Clayden, HIV i-Base

A poster from the CHER study group looked at Bacille-Calmette-Guerin (BCG)-related complications in this cohort and in a comparator group of HIV-negative infants born to mothers participating in a vaccine trial.

In this study 292 HIV-positive infants 6 to12 weeks of age were randomised to immediate ART and 125 to deferred ART. The HIV-negative infants in the study were born to HIV-positive (n=125) and HIV-negative mothers (n=125).

All children received BCG vaccination at birth as is standard in South Africa. Signs of local reaction to BCG and other clinical events were compared among the infants.

This was data after a median follow up of 40 weeks.

The investigators reported that the prevalence of regional BCG-adenitis among the HIV-positive infants was 33/417, 7.9% (5.5 to 10.9), of which13 (10.4%), were in the deferred arm and 20 (6.9%) in the early ART arm (OR 1.6, 0.8 to 3.3; p =0.22). By comparison none of the HIV-negative infants had local BCG-adenitis.

The majority, 31/33 (93.9%) of cases of BCG-related regional adenitis occurred following initiation of HAART, which suggested IRIS. 2 infants in the deferred arm had pre-existing adenitis.

There was no difference in the development of IRIS-related BCG-adenitis between the early-HAART 20/292 (6.8%), p= 0.48 and the deferred HAART 11/125 (8.8%) groups.

Out of the 33 infants with BCG-adenitis, 3 died (2 in the deferred arm and 1 in the early ART group). One of the deaths (in the deferred arm) was considered to be associated with BCG disease.

The investigators noted that the infants in the deferred arm received more concomitant therapy than in the early ART group (7/13 infants vs 4 /20 for TB treatment). Of 8 infants that received 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.

In the discussion section of this poster the investigators explained that in May 2007, the WHO revised its guidelines for BCG vaccination for children born to HIV-positive mothers. WHO recommended that it should not be given to children known to be HIV-positive. By that time, the CHER trial was fully recruited.

The investigators concluded:

  • HIV-positive infants receiving BCG at birth have a high risk of BCG-associated IRIS.
  • Associated factors are lower CD4 count/percentage and low WAZ.
  • In infants with baseline CD4 >/=25%, early ART is associated with significantly less IRIS than deferred ART
  • Children in the deferred arm developed IRIS sooner after ART initiation with longer time to resolution
  • TB drugs +/- steroids did not improve the time to resolution.

They wrote: “Early ART is associated with a significant reduction in BCG-associated IRIS, probably by limiting the degree of CD4 depletion.”


Rabie H Violari A, Madhi S et al. Complications of BCG vaccination in HIV-infected and -uninfected children: CHER Study. 15th CROI. February 2008. Boston, USA. Poster abstract 600.

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