Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy

Objective: To investigate the outcome in children perinatally infected with HIV-1 whose mothers received zidovudine (ZDV) monotherapy in pregnancy. Design: Observational retrospective study of a prospectively recruited coho rt. Setting: Italian Register for HIV Infection in Children. Patients: A group of 216 children perinatally infected with HIV-1, born in 1992-1997 and derived prospectively from birth: 38 children had mothers rec eiving ZDV monotherapy and for 178 children the mothers received no antiret roviral treatment during pregnancy. Main outcome measures: The estimated probability of developing severe disea se or severe immune suppression, survival probability [95% confidence inter val (CI)] within 3 years, and the hazard ratio (95% CI), adjusted for year of birth, maternal clinical condition at delivery, birthweight and treatmen ts (Pneumocystis carinii pneumonia chemoprophylaxis and/or antiretroviral t herapy before the onset of severe disease, severe immune suppression or dea th) were compared. Results: Comparison of HIV-1-infected children whose mothers were treated w ith ZDV with children whose mothers were not treated showed that the former group had a higher probability of developing severe disease [57.3% (95% CI 40.9-74.3) versus 37.2% (95% CI 30.0-45.4); log-rank test 7.83, P = 0.005; adjusted hazard ratio 1.8 (95% CI 1.1-3.1)] or severe immune suppression [ 53.9% (95% CI 36.3-73.5) versus 37.5% (95% CI 30.0-46.2); log-rank test 5.5 8, P = 0.018; adjusted hazard ratio 2.4, (95% CI: 1.3-4.3)] and a lower sur vival [72.2% (95% CI 50.4-85.7) versus 81.0% (95% CI 73.7-86.5); log-rank t est 4.23, P = 0.039; adjusted hazard ratio of death 1.9 (95% CI 1.1-3.6)]. Conclusions: This epidemiological observation could stimulate virologic stu dies to elucidate whether this rapid progression depends on in utero infect ion or transmission of resistant virus. Findings may suggest a need to hast en HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggre ssive antiretroviral therapy in those found to be infected. (C) 1999 Lippin cott Williams & Wilkins.