Long-term outcomes in adolescents perinatally infected with HIV-1 and followed up since birth in the French perinatal cohort (EPF/ANRS CO10).

BACKGROUND. Increasing numbers of children perinatally infected with human immunodeficiency virus (HIV) are reaching adolescence, largely because of advances in treatment over the past 10 years, but little is known about their current health status. We describe here the living conditions and clinical and immunovirologic outcomes at last evaluation among this pioneering generation of adolescents who were born before the introduction of prophylaxis for vertical transmission and whose infections were diagnosed at a time when treatment options were limited. METHODS. The eligible population consisted of HIV-1-infected children who were born before December 1993 and who were included at birth in the prospective national French Perinatal Cohort (EPF/ANRS CO10). RESULTS. Of the 348 eligible children, 210 (60%; median age, 15 years) were still alive and regularly followed up. Current treatment was highly active antiretroviral therapy (HAART) in 77% and 2 nucleoside analogues in 5.0%; 16% had stopped treatment, and 2% had never been treated. The median CD4 cell count was 557 cells/microL, and 200 cells/microL was exceeded in 94% of patients. The median viral load was 200 copies/mL. Viral load was undetectable in 43% of the adolescents and in 54.5% of those receiving HAART. Median height, weight, and body mass index were similar to French reference values for age, and school achievement was similar to nationwide statistics. Better immunologic status was associated with being younger and with having begun HAART earlier. Undetectable viral load was associated with maternal geographic origin and current HAART. CONCLUSIONS. Given the limited therapeutic options available during the early years of these patients' lives and the challenge presented by treatment adherence during adolescence, the long-term outcomes among this population are encouraging.

Reproductive behaviour of HIV-infected women living in France, according to geographical origin.

Pregnancy rates were compared before and after HIV diagnosis according to geographical origin (sub-Saharan Africa versus Europe) among 533 HIV-infected women followed in the French SEROCO/SEROGEST cohorts between 1988 and 1996. Among European women, the incidence of deliveries and terminations decreased, respectively, by nearly twofold and fourfold after HIV diagnosis. Conversely, the pregnancy incidence increased among African women with fewer than two children. This study should help refine the reproductive counselling and management of HIV-infected women in France.

Pregnancy and progression to AIDS: results of the French prospective cohorts. SEROGEST and SEROCO Study Groups.

OBJECTIVE: To investigate whether pregnancy accelerates HIV-1 disease progression. METHOD: In two large French SEROCO and SEROGEST prospective cohorts of HIV infected patients, the progression to AIDS in 365 women with a known date of HIV-1 seroconversion was examined by comparing those who delivered after HIV infection (n = 241) with those who did not become pregnant while HIV-infected (n = 124). RESULTS: The crude relative risk of developing AIDS associated with pregnancy was 0.7 [95% confidence interval (CI), 0.4-1.2]. Adjustment for age at seroconversion, the CD4+ cell percentage at entry, and the method used to date seroconversion did not modify the results (adjusted relative risk, 0.7; 95% CI 0.4-1.2). CONCLUSIONS: No deleterious effect of pregnancy on progression from seroconversion to AIDS was found. This result has important implications for the counselling of HIV-infected women of child-bearing age.

Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group.

OBJECTIVE: To describe the spontaneous course, before the introduction of highly active antiretroviral therapy (HAART), of HIV-1 RNA during the AIDS-free period of the disease. To assess the predictive value of changes in HIV-1 RNA levels. DESIGN: A total of 330 patients with a known date of infection followed in the SEROCO cohort. METHODS: HIV-1 RNA levels (threshold, 200 copies/ml) were evaluated from 2243 frozen sera obtained from enrolment until the onset of AIDS or until February 1996. Lowess curves were used to describe the variations of viraemia during follow-up. A Cox regression model was used to assess the predictive value of early and updated CD4 cell count and viral load. RESULTS: In addition to a lower early viral load, patients who remained AIDS-free had, on average, a longer period of viral load decrease after infection (36 versus 18 months), followed by a slower viral load increase compared with those who progressed to AIDS. A true plateau-phase after the seroconversion period, lasting approximately 4 years, was identified only in patients who remained AIDS-free for at least 90 months. In multivariate analysis, both early viral load and later changes were significant predictors of progression to AIDS. A decrease in the CD4 cell count to less than 200 cells/microl and the onset of a group B condition remained significant predictors of progression. CONCLUSION: Our study extends to the early post-seroconversion phase the prognostic value of extracellular HIV-1 RNA levels. Moreover, our data suggest that, in most HIV-infected individuals, a progressive loss of control of viral replication arises during the early years of HIV-1 infection.

HIV-1-related encephalopathy in infants compared with children and adults. French Pediatric HIV Infection Study and the SEROCO Group.

OBJECTIVE: To characterize the specificities of HIV-1-related encephalopathy in children. METHODS: Comparison of patients from the French Perinatal Cohort of children born to HIV-1-infected mothers and followed from birth with the French SEROCO Cohort of adults with a known date of infection. Our study examines 1) the characteristics of encephalopathy with onset before 1 year, after 1 year, and in adults, and 2) the maternal and birth characteristics of infants who developed AIDS before 1 year and went on to develop either encephalopathy or opportunistic infection. RESULTS: The incidence of encephalopathy was higher in children than in adults during the first year (9.9% versus 0.3%) and intermediate during the second year (4.2% versus 0%) after infection but was similar thereafter (less than 1% per year in each group). The resulting cumulative incidence at 7 years postinfection reached 16% in children and 5% in adults. Encephalopathy that developed before 1 year 1) was more frequently an isolated symptom of AIDS, 2) was associated with a reduction of intrauterine brain growth, 3) was associated with a very low level of HIV-1 RNA in CSF, 4) occurred at a higher level of immunocompetence after taking into account the decrease in CD4 lymphocytes with age, and 5) was not prevented by zidovudine treatment during gestation. CONCLUSIONS: Early encephalopathy in infants has a different pathophysiologic mechanism than that occurring in children, which in turn shows similarities with that observed in adults. Early encephalopathy is probably related to the occurrence of pathologic events during late fetal life.

CCR5 delta32 deletion and reduced risk of toxoplasmosis in persons infected with human immunodeficiency virus type 1. The SEROCO-HEMOCO-SEROGEST Study Groups.

This study attempted to determine whether the CCR5 Delta32 deletion affected progression to certain first AIDS-defining illnesses in human immunodeficiency virus type 1-infected patients enrolled in the French SEROCO/HEMOCO/SEROGEST cohorts. Toxoplasmosis onset as a first AIDS-defining illness was significantly delayed in 253 heterozygous patients, compared with 1404 wild type patients. The relative risk of toxoplasmosis associated with heterozygosity was 0. 39 (95% confidence interval, 0.16-0.96) after adjustment for age, CD4 cell count, and primary specific prophylaxis. A nonsignificant protective trend was observed with regard to the onset of mycobacterial, cytomegalovirus, and herpesvirus diseases, but these events were less frequent than toxoplasmosis. Progression to other conditions (e.g., wasting, non-Hodgkin's lymphoma, Kaposi's sarcoma) was similar in the 2 groups as was the frequency of toxoplasmosis as a subsequent AIDS-defining illness. As chemokines are involved in numerous infectious processes, the Delta32 deletion could delay progression to certain opportunistic infections such as toxoplasmosis.

Perinatal HIV-1 transmission: interaction between zidovudine prophylaxis and mode of delivery in the French Perinatal Cohort.

CONTEXT: It is unclear whether elective cesarean delivery may have a protective effect against the transmission of human immunodeficiency virus 1 (HIV-1). OBJECTIVE: To investigate whether mode of delivery has an impact on perinatal HIV-1 transmission in the presence of zidovudine prophylaxis. DESIGN: A prospective cohort study. SETTING: The 85 perinatal centers in the French Perinatal Cohort, from 1985 to 1996. PATIENTS: A total of 2834 singleton children born to mothers with HIV-1 infection. MAIN OUTCOME MEASURE: Human immunodeficiency virus 1 infection of the infant. RESULTS: No zidovudine was used in 1917 pregnancies and zidovudine prophylaxis was used in 902 pregnancies. Cesarean deliveries were performed in 10.9% on an emergent basis and in 8.3% electively, prior to labor or membrane rupture. In 1917 mothers who did not receive zidovudine, of 1877 with information on mode of delivery, 17.2% transmitted HIV-1 to their child. Risk factors statistically significantly associated with transmission were maternal p24 antigenemia, cervicovaginal infections during pregnancy, amniotic fluid color, and rupture of membranes 4 hours or more before delivery. Mode of delivery was not related to transmission. In 902 mothers receiving zidovudine, transmission was 6.4% in 872 with information on mode of delivery, and elective cesarean delivery (n = 133) was associated with a lower transmission rate than emergent cesarean or vaginal delivery (0.8%, 11.4%, and 6.6%, respectively; P=.002). In a multivariate analysis of all mother-child pairs, including obstetrical risk factors, maternal p24 antigenemia, and zidovudine prophylaxis, interaction between mode of delivery and zidovudine prophylaxis was significant (P=.007). In the multivariate analysis of pregnancies with zidovudine prophylaxis, factors related to transmission rate were maternal p24 antigenemia, amniotic fluid color, and mode of delivery. Adjusted odds ratios (95% confidence intervals) were 1.6 (0.7-3.6) for emergent cesarean delivery and 0.2 (0.0-0.9) for elective cesarean delivery (P = .04) in comparison with vaginal delivery. CONCLUSIONS: We observed an interaction between zidovudine prophylaxis and elective cesarean delivery in decreasing transmission of HIV-1 from mother to child. This observation may have clinical implications for prevention.

Obstetric factors and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohorts. SEROGEST French Pediatric HIV Infection Study Group.

OBJECTIVE: We attempted to determine whether the risk of mother-to-child transmission of human immunodeficiency virus type 1 is related to events in pregnancy, labor, and delivery. STUDY DESIGN: In a prospective multicenter cohort study of human immunodeficiency virus type 1-infected mothers and their children, we studied pregnancy histories, labor (including gestational age, induction, membrane rupture, length of labor, intrapartum procedures, bleeding, infection, antiseptic technique, and antiretroviral therapy), and conditions of delivery. RESULTS: Among 1632 singleton infants, 310 were confirmed infected with human immunodeficiency virus type 1 at age 18 months (19.0% +/- 1.9%). Procedures (in particular, amniocentesis and amnioscopy) and sexually transmitted diseases during pregnancy, preterm delivery, premature membrane rupture, hemorrhage in labor, and bloody amniotic fluid were associated with increased transmission. Transmission was not related to mode of delivery or to the conditions of labor and delivery. CONCLUSIONS: Transmission was not decreased after emergency or elective cesarean section. Most risk factors either were rare or appeared poorly amenable to obstetric management, with the exception of invasive procedures, which should be avoided.

Maternal factors associated with perinatal HIV-1 transmission: the French Cohort Study: 7 years of follow-up observation. The French Pediatric HIV Infection Study Group.

A nationwide, longitudinal study of infants born to human immunodeficiency virus-seropositive mothers has been under way in France since 1986. After 7 years of follow-up observations, we will update our assessment of the transmission rate in France and analyze, on a larger number of mother-infant pairs, the influence of maternal factors. Among the 848 pairs included in this analysis, the transmission rate was 20.2 +/- 2.7%. The transmission rate has remained stable with time and was not influenced by the mode of delivery, the mode of maternal infection, or the mother's ethnic origin. It was twice as high among the breast-fed infants as among the bottle-fed infants (40 vs. 19%, p < 0.04). Two factors were identified in a multivariate analysis (that did not include lymphocyte subset counts and the mode of feeding) as being associated with an increased risk of maternofetal transmission: p24 antigenemia (odds ratio = 3.1, confidence interval, = 1.5-6.2; p < 0.003) and elevated maternal age (p < 0.05). In the subgroup of 277 women whose absolute CD4+ lymphocyte counts at the time of delivery were available, the risk of transmission increased gradually from 15% of counts of > 600 CD4+ cells to 43% at counts of < 200. The risk of transmission was also related to the percentage of CD8+ cells, but each of the two factors seemed to play an independent role: the risk was lowest (12%) when the CD4+ cell count was > 500 and the proportion of CD8+ cells was < or = 40%, and was highest (50%) for values < 200 and > 40%.(ABSTRACT TRUNCATED AT 250 WORDS)