15th International AIDS Conference Bangkok, Thailand — July 11-July 16, 2004

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrB12

H Zar¹, M Cotton², C Lombard³, J Karpakis², S Strauss¹, G Hussey¹, H S Schaaf², H Rabie^2
1University of Cape Town, Cape Town, South Africa; ²Stellenbosch University, Tygerberg, South Africa; ³MRC, Tygerberg, South Africa

BACKGROUND: Both tuberculosis and Pneumocystis pneumonia are major opportunistic infections in HIV-infected African children. The effect of INH prophylaxis on mortality and TB incidence in HIV infected children has not been studied.

AIMS: To investigate the effect of long term INH prophylaxis on mortality in HIV-infected children from a high TB prevalence area. Secondary outcomes included investigation of the incidence of TB.

METHODS: A two-centre prospective double blind placebo controlled trial in Cape Town, South Africa, comparing isoniazid (INH) versus placebo given with trimethoprim-sulphamethoxazole (TMP-SMX) either daily or three times weekly in HIV-infected children aged 8 weeks or older. INH was given according to the frequency of the TMP-SMX schedule.

RESULTS: Enrolment began in January 2003. Interim analysis performed in December, 2003 found 21 deaths in 148 (14.1%) subjects who had 1 month or more of follow-up. The mortality rate amongst those on placebo [16 of 21 (76.2%)] was significantly higher than those on INH by “intent to treat” (p = 0.004) and “time on treatment” analysis using person-time exposure (p = 0.0005). The survival benefit appeared within 50 days, occurred in all CDC categories of clinical disease severity and in both study centres. Of 14 cases of tuberculosis, 9 were in the placebo and 5 in the INH group (intent to treat analysis: p = 0.077; log-rank).

CONCLUSION: INH prophylaxis has an early and significant survival benefit and reduces TB incidence in HIV-infected children. Based on these results and the recommendation of the data safety monitoring board, the placebo arm of the study has been discontinued.

Funding: Rockefeller Foundation

040711
LbOrB12

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