Longitudinal trajectories of neurocognitive test performance among individuals with perinatal HIV-infection and -exposure: adolescence through young adulthood.

There are an estimated 2.1 million youth less than 15 years of age living with HIV globally (the majority perinatally HIV-infected [PHIV]) and millions more perinatally HIV-exposed uninfected (PHEU) youth who are expected to survive through adolescence and into adulthood. Transitioning from adolescence to young adulthood requires adaptation to more demanding social interactions, academic pressures, and individual responsibilities which place distinct demands on neurocognitive functions. This study examined longitudinal trajectories of neurocognitive test performance in the domains of processing speed (PS), working memory (WM), and executive functioning (EF) among PHIV and demographically similar PHEU from adolescence through young adulthood. Data for this paper come from four time points, spanning approximately 10 years, within the Child and Adolescent Self-Awareness and Health Study (CASAH). Youth age ranged from 15 to 29 years. Longitudinal linear mixed effect models were computed for each test. Few differences in performance were found on tests of EF and WM between PHIV and PHEU youth as they aged, though PHEU youth showed significantly better PS as they aged than PHIV youth. Future research is needed to understand these vulnerable youth's neurocognitive trajectories as a function of HIV infection and -exposure, biological functions and psychosocial stressors.

Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected women.

Among women with HIV infection, pregnancy is a time when maintenance of maternal health and reduction of vertical HIV transmission are primary concerns. Few studies have examined adherence to Antiretroviral Treatment (ART) during pregnancy and in the postpartum period when the demands of childcare may significantly interfere with women's self-care behaviors. This study examined ART use and adherence in HIV-infected pregnant and postpartum women participating in the Women and Infants Transmission Study (WITS-IV) in the US. Adherence was assessed through a self-report interview during the third trimester of pregnancy and six-month postpartum. Data were also collected on demographics, biomedical markers and health related symptoms. During the third trimester visit, 77% (309/399) of women completed the self-report adherence measure; 61% (188/309) reported complete adherence. Factors associated with non-adherence included advanced HIV disease status, higher HIV-RNA viral load, more health-related symptoms and alcohol and tobacco use. At six-month postpartum, 55% (220/399) completed the measure; 44% (97/220) of these women reported complete adherence. Factors associated with non-adherence during the postpartum period were ethnicity, more health-related symptoms and WITS clinical site. Results of multivariate analyses using Generalized Estimated Equation analyses across the two visits revealed that more health-related symptoms, higher HIV-RNA viral load, increased alcohol use and clinical site were independently associated with ART non-adherence. These analyses indicate that medication adherence is more likely during pregnancy than postpartum in HIV-infected women, perhaps provoked by motivation to reduce vertical transmission and/or intensive antepartum surveillance. Further investigation is warranted to clarify factors implicated in women's decision-making process regarding ART medication adherence.

Head growth and neurodevelopment of infants born to HIV-1-infected drug-using women.

OBJECTIVE: To describe neurodevelopment and head growth in HIV-1-infected and exposed uninfected infants with and without in utero exposure to opiates and cocaine. METHODS: Using data from a multicenter cohort study of HIV-1-infected women and their children, the authors fit repeated measures regression models to estimate the effects of HIV-1 infection and in utero hard drug exposure on head circumference and Bayley Scales of Infant Development standard scores during the first 30 months. RESULTS: Of the 1,094 infants included in the analysis, 147 (13%) were HIV-1-positive and 383 (35%) were exposed in utero to opiates or cocaine (drug-positive). Mean 4- month Bayley mental scores were lower in infants with only HIV-1 positivity (HIV-positive and drug-negative) (-8.2 points, p < 0.0001) or only drug exposure (HIV-negative and drug-positive) (-4.4 points, p = 0.0001) and tended to be lower in infants with both factors (HIV-positive and drug-positive) (-3.7 points, p = 0.0596), compared with those who were HIV-1-negative and not drug exposed (HIV-negative and drug-negative). However, by 24 months of age, there was no longer a decrement among HIV-negative and drug-positive infants, whereas HIV-1 infection was still associated with a decrement relative to uninfected infants. Similar results were seen for Bayley motor scores and for head circumference Z scores. CONCLUSIONS: HIV-1 infection and in utero opiate and cocaine exposure decrease birth head circumference and slow neurodevelopment at 4 months. At 24 months of age, however, only HIV-1 infection is associated with decreased neurodevelopment and head circumference. There may be some postnatal recovery from the effects of in utero hard drug exposure. Importantly, the detrimental effects of HIV-1 positivity and maternal hard drug use on neurodevelopment at 4 months are not additive, although they are additive for birth head circumference.

Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment. The Women and Infant Transmission Study Group.

BACKGROUND: Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified. METHODS: Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures. RESULTS: Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13). CONCLUSION: Early HIV-1 infection increases a child's risk for poor neurodevelopmental functioning within the first 30 months of life.

Increases in plasma atrial natriuretic peptide concentration antedate clinical evidence of preeclampsia.

Atrial natriuretic peptide (ANP) concentrations are typically elevated in hypervolemic states. However, ANP levels have been reported to be increased in the peripartum period in women with preeclampsia, a disorder characterized by central hypovolemia. We postulated that ANP levels are elevated in preeclamptic patients before clinically evident disease. ANP concentrations were determined in three groups: uncomplicated pregnancies, pregnancies complicated by preeclampsia, and non-pregnant reproductive-aged women. The former groups were matched for gestational age at plasma sampling and delivery. The plasma samples, obtained prospectively from each patient during the first, second, and third trimesters and within 72 h postpartum, were frozen before RIA. A significant gestational increase in ANP was noted in both groups of pregnant women, with third trimester levels exceeding first trimester levels (P less than 0.05). Consistent with previous reports, ANP levels were elevated in overtly preeclamptic patients vs. matched controls in the third trimester. The ANP concentration was also significantly increased during the second trimester in women destined to develop preeclampsia. Postpartum ANP values decreased in the preeclamptic group to approach the level in normal patients postpartum. Thus, it appears that the stimuli of ANP secretion differ in uncomplicated and preeclamptic patients. Moreover, an elevation of plasma ANP is detectable before the onset of clinical evidence of preeclampsia.

Severe acidosis and subsequent neurologic status.

To examine the relationship between severe acidosis at birth and evidence of subsequent neurologic dysfunction, a 4-year review was performed encompassing 15,528 neonates. One hundred forty-two (0.91%) of these neonates had an umbilical cord arterial pH less than or equal to 7.05 with a base deficit greater than or equal to mEq/L. Neurologic assessments found 101 of 110 term neonates (91.8%) and 17 of 32 preterm neonates (53.1%) with severe acidosis to be free of neurologic deficits at the time of hospital discharge. Follow-up developmental evaluation data were available for 7 of 9 term neonates and 8 of 15 preterm neonates with abnormal examinations. Although 5 term and 6 preterm infants demonstrated mild developmental delays or mild tone abnormalities in the first year of life, none exhibited a major motor or cognitive abnormality at 12 to 24 months of age. Consequently, acidosis in umbilical cord blood, even when severe, is a poor predictor of subsequent neurologic dysfunction.