C. Fundarò

Features of children perinatally infected with HIV-1 surviving longer than 5 years. Italian Register for HIV Infection in Children

Children infected with HIV do not necessarily develop AIDS to a set pattern but can be divided into long-term and short-term survivors. We examined long-term survival in children perinatally infected with HIV-1. Out of a total of 624, we studied 182 children who survived longer than 5 years (long-term survivors [LTS]) and 120 children who died of HIV-1-related disease before 5 years (defined as short-term survivors [STS]). 28 (15%) LTS were symptomless (Centers for Disease Control [CDC] P-1 children). 154 (85%) had symptoms (CDC P-2). The proportion of LTS with less than 0.2 x 10(9)/CD4 cells per L was 24/116 (21%) at 61-72 months, rising to 11/26 (41%) at more than 96 months. On at least one occasion, p24 antigenaemia was observed in 112 (62%) LTS. Annual rate of CD4 cell loss was lower in LTS (25% [95% CI: 21-29]) than in STS (53% [45-60]) and in LTS symptomless or with solitary P-2A signs (17%; [13-21]) than in LTS with severe manifestations (30% [25-35]). A new outlook emerges. A substantial number of children do survive after early childhood; severe diseases; low CD4 cell numbers, and p24 antigenaemia do not necessarily preclude long-term survival. The study shows that a CD4 cell decrease early in life can be predictive of outcome.

Features of children perinatally infected with HIV‐1 surviving longer than 5 years

ly surveillance for the occurrence of diarrhea. Stool specimens collected at the onset of diarrhea were evaluated for enteropathogens. Infants who were infected with HIV were compared with uninfected infants. Subjects: Infants born to HIV-infected women at the University of Maryland Hospital, Baltimore, were recruited at 0 to 3 months of age. This analysis included 58 infants enrolled in the cohort and followed up at least 15 months (unless death intervened) whose HIV status was established (18 HIV-infected infants and 40 HIVuninfected infants). Measurements and Results: The overall incidence of diarrhea in HIV-infected infants was 3.2 episodes per 12 child-months compared with 1.5 episodes per 12 childmonths among HIV-uninfected infants (incidence density ratio, 2.2; P < 0.05). An enteropathogen was identified in stool specimens collected during 20% of diarrhea1 episodes occurring in HIV-infected infants and during 25% of diarrhea1 episodes occurring in HIV-uninfected infants. Episodes that persisted for 14 days or longer were significantly more common among HIV-infected infants. The peak incidence of diarrhea occurred at 0 to 5 months of age for HIV-infected infants compared with 6 to 1 I months for HIV-uninfected infants. Early onset of diarrhea (< 6 months old) in HIV-infected infants was associated with the later development of persistent episodes of diarrhea, and those with persistent episodes had more severe HIV infection, characterized by a significantly higher frequency of opportunistic infections and lower CD4+ T lymphocyte counts by 1 year of age. Conclusions: Both acute and persistent episodes of diarrhea are major sources of morbidity in HIVinfected infants. Moreover, persistent diarrhea is a marker for rapid progression of HIV disease.

Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy The Italian Register for HIV Infection in Children*

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 cohort. 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 receiving ZDV monotherapy and for 178 children the mothers received no antiretroviral treatment during pregnancy. MAIN OUTCOME MEASURES The estimated probability of developing severe disease or severe immune suppression, survival probability [95% confidence interval (CI)] within 3 years, and the hazard ratio (95% CI), adjusted for year of birth, maternal clinical condition at delivery, birthweight and treatments (Pneumocystis carinii pneumonia chemoprophylaxis and/or antiretroviral therapy before the onset of severe disease, severe immune suppression or death) were compared. RESULTS Comparison of HIV-1-infected children whose mothers were treated with 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 5.58, P = 0.018; adjusted hazard ratio 2.4, (95% CI: 1.3-4.3)] and a lower survival [72.2% (95% CI 50.4-85.7) versus 81.0% (95% CI 73.7-86.5); log-rank test 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 studies to elucidate whether this rapid progression depends on in utero infection or transmission of resistant virus. Findings may suggest a need to hasten HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggressive antiretroviral therapy in those found to be infected.

HIV-I infection in perinatally exposed siblings and twins. The Italian Register for HIV Infection in Children.

In a multicentre study on perinatal HIV-I infection including 1493 children born from 1471 pregnancies to 1415 infected mothers, 22 twin pairs and 56 sibships (115 children) were recorded. The frequency of twin pregnancies was 1.5 (22/1471) and 3.9% (56/1415) seropositive women had more than one at risk pregnancy. In 18 twin pairs with a known infection status nine of the 36 children (25%) were infected. Discordance in infection status was present in only one (5.5%) dizygous pair. A high relative risk of infection (23.1) in a twin was observed when the other was infected. Infection was unrelated to gestational age, mode of delivery, or birth weight. Infection status was defined in 41 sibships (84 children including one first born twin pair and one third born child). When the first born was infected, 11/26 (42.3%) second born children were also infected, whereas this happened in only 2/16 (12.5%) second or third born children when the first born was uninfected. Two out of nine first born (22.2%) and 5/21 (23.8%) second born children prospectively followed up from birth acquired the infection. Results of this study demonstrate that neither twin nor second pregnancies are at increased risk of mother to child HIV-I transmission. Overall data suggest that non-casual factors in mother and/or child influence perinatal infection.

Cancer Rates After Year 2000 Significantly Decrease in Children With Perinatal HIV Infection: A Study by the Italian Register for HIV Infection in Children

PURPOSE To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. PATIENTS AND METHODS An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. RESULTS Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.