Contribution of bacterial sepsis to morbidity in infants born to HIV-infected Haitian mothers

BACKGROUND: Haiti is a country with a heavy burden of HIV infection in childbearing women. Previous studies have shown that early infant deaths are common in children of HIV-infected women. This study was designed to define the rates of and risk factors for systemic bacterial and mycobacterial infection in such children and to identify the causative agents. METHODS: A cohort of 120 children born to HIV-infected mothers between May 2001 and December 2003 were prospectively observed to 15 months of age. They received comprehensive pediatric care at the GHESKIO Centers. Children were assigned to being HIV-infected by serology, RNA detection, and/or defining clinical illnesses. Blood cultures were obtained before giving antibiotics in children who were febrile or chronically ill. Blood cultures also were obtained at selected visits on well children. RESULTS: The mortality rate in the first 15 months was high, 22 of 106 (207/1,000 live births) in these children. Sixteen (70%) deaths were within 6 months of birth. Fourty-eight blood cultures had clinically significant organisms of which 38 were Staphylococcus aureus. Blood cultures were more likely to be positive in symptomatic and in HIV-infected children. CONCLUSIONS: Despite perinatal HIV treatment, mortality in children born to HIV-infected mothers remained high. Bacteremia, particularly with Staphylococcus aureus, is a partial explanation for excess illness.     

Clinical mitochondrial dysfunction in uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues

Clinical and biological observations of mitochondrial dysfunction in children exposed to zidovudine (azidothymidine, AZT) during the perinatal period rapidly followed similar observations in animal experiments. To date, two different disorders have been identified. The first, asymptomatic hyperlactatemia, is observed during treatment in one third of exposed newborns, and is reversible with treatment cessation. In rare cases, it is associated with symptomatic acidosis. Regression may be slow, taking up to several months after the end of the treatment. The long-term clinical consequences of this biochemical disturbance are unknown. The second disorder involves severe neurological symptoms, which become clinically detectable during the first 2 years of life. These symptoms are associated with a series of biochemical and ultrastructural changes consistent with persistent mitochondrial dysfunction. This latter phenomenon is rare, and affects only 0.3-0.5% of exposed children in the French pediatric cohort, in which observations continue. Despite initial controversy, several similar observations in other cohorts have since confirmed its occurrence. The pathophysiology of these two mitochondrial dysfunctions may differ. Continued efforts to identify and understand clinical mitochondrial toxicities are essential, given the intensification and diversification of perinatal prophylaxis strategies, and the number of pregnant women potentially involved.     

Repeated polymerase chain reaction complementary to other conventional methods for early detection of HIV infection in infants born to HIV-infected mothers

The efficacy of a polymerase chain reaction (PCR) method for early detection of human immunodeficiency virus (HIV) in infants at risk for HIV infection was assessed. The PCR method was added to the routine laboratory test programme in these patients in 1988. PCR was performed in a total of 26 children at risk (age range 2 days to 58 months), including 17 infants born to HIV-infected mothers, who were followed up clinically from the time of birth for a mean period of 23 months (range 6 to 54) in a prospective study. Twelve children were PCR-positive. Eight had AIDS, ARC or symptoms suggestive of HIV infection. All these patients had at least one culture positive for HIV (6/8) and/or one positive serum p24-antigen test (5/8). One child was repeatedly PCR positive, but asymptomatic as well as virus- and antigennegative. Three asymptomatic children with a single positive PCR result were PCR negative in subsequent tests. Fourteen children with negative PCR did not show clinical or immunological signs suggestive of HIV infection. Their cultures for HIV and antigen-p24 assays were negative. It is concluded that in addition to clinical and immunological parameters PCR is a useful technique for diagnosis of HIV infection in infants born to HIV-infected mothers. However, in case of negative HIV cultures and/or serum p24-antigen tests, single positive PCR results in asymptomatic patients must be interpreted with caution and should be confirmed by repeated tests.     

Energy expenditure and intake in infants born to lean and overweight mothers

We investigated the contributions of low energy expenditure and high energy intake to excessive weight gain in infants born to overweight mothers. The subjects were infants of 6 lean and 12 overweight mothers, recruited soon after birth. Total energy expenditure and metabolizable energy intake were measured with a new doubly labeled water method over a period of seven days when the infants were 3 months of age, and the postprandial metabolic rate was measured by indirect calorimetry when the infants were 0.1 and 3 months of age. The results were related to weight gain in the first year of life. No significant difference was observed between infants who became overweight by the age of one year (50 percent of infants born to overweight mothers) and those who did not, with respect to weight, length, skinfold thicknesses, metabolic rate at 0.1 and 3 months of age, and metabolizable energy intake at 3 months. However, total energy expenditure at three months of age was 20.7 percent lower in the infants who became overweight than in the other infants (means +/- SE, 256 +/- 27 and 323 +/- 12 kJ per kilogram of body weight per day; P less than 0.05). This difference could account for the mean difference in weight gain. These data suggest that reduced energy expenditure, particularly on physical activity, was an important factor in the rapid weight gain during the first year of life in infants born to overweight mothers.     

Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis

Although prevention of mother-to-child HIV transmission by antiretroviral drugs has been shown to be effective, the short- and long-term effects of treatment are not well known. Several reports suggest that antiretroviral drugs act not only by inhibiting viral replication, but also by improving antiviral immunity. In particular, treatment with nucleoside analogs was found to increase CD40 ligand (CD40L; CD154) levels, an inducible molecule expressed on activated T lymphocytes. The present study investigated potential immunostimulatory effects of antiretroviral treatment (ART) in uninfected HIV-exposed infants, receiving either ante- or postnatal therapy to reduce the transmission rate. To this end, we analyzed CD40L expression in unstimulated lymphocytes from peripheral blood samples of uninfected infants vertically exposed to HIV and subjected to ART. The CD45 PanLeucogating strategy was applied in flow cytometry to analyze the lymphocytes of 41 cases and 64 age-matched infants, taken as control. We found increased CD154 expression on both CD4+ and CD8+ lymphocytes in ART-treated infants, compared with the controls. CD154 was apparently functional, because the expression of CD86 on monocytes was enhanced; moreover, inhibition of the CD40-CD40L interaction produced downmodulation of CD86. From these results, we conclude that CD4+ and CD8+ lymphocytes of HIV-exposed noninfected infants, who have been exposed to antiretroviral drugs in fetal and early life, display enhanced CD154 expression and costimulatory activity.     

Longitudinal anthropometric changes in HIV-infected and HIV-uninfected men

BACKGROUND: Although morphologic abnormalities are common among HIV-infected persons receiving highly active antiretroviral therapy (HAART), longitudinal comparative body shape changes among HAART-treated HIV-infected men versus HIV-seronegative men of similar age remain unclear. METHODS: Since September 1999, men enrolled in the Multicenter AIDS Cohort Study underwent body mass index (BMI) and circumference measurements of the waist, hip, thigh, and arm at each semiannual visit. Changes in these measurements that occurred between 1999 and 2003 among HIV-infected men were compared with measurements of HIV-seronegative men using linear mixed effects regression models. The HIV-infected men were further stratified by treatment group (no antiretroviral therapy [ART], monotherapy or combination [mono/combo] ART, or HAART). Analyses were adjusted for age, nadir CD4 cell count, and BMI (for circumference measurements). RESULTS: Over the 4-year observation period, mean BMI increased significantly among the 392 HIV-seronegative men (0.12 kg/m/y; P < 0.001) but did not change in the 3 HIV-infected groups (combined n = 661). Mean waist and hip circumferences increased significantly in all groups. Hip circumferences increased more slowly in the HIV-positive HAART-treated group (n = 488) than in the HIV-seronegative group (0.18 vs. 0.49 cm/y; P < 0.001), however, yielding a more rapid increase in the waist/hip ratio in the HIV-positive, HAART-treated group over time (0.005 per year; P < 0.001). CONCLUSIONS: The increased rate of change in waist/hip ratio in HIV-infected men receiving HAART compared with HIV-seronegative men is attributable to slower increases in hip circumference rather than an increased rate of change in waist circumference. These findings underscore the importance of body fat composition changes in the peripheral compartment relative to the central compartment among HIV-infected men receiving HAART.     

Delayed visuomotor development in children born to adolescent mothers

The objective of the present study was to determine visuomotor development of children born to adolescent mothers and to compare it with that observed in those born to adult mothers. The sample included 59 urban Mestizo children, 7–8 years of age, who were born to adolescent mothers, and 73 urban Mestizo children of the same age, who were born to adult mothers (>20 years). Visuomotor development was assessed using the Bender test. Children born to adolescent mothers had a higher number of errors in the Bender Gestalt scores compared to those obtained by children born to adult mothers. Items of perseverance and integration in the Bender-Gestalt test were the most affected in children born to adolescent mothers. Of the children born to adolescent mothers, 13.8% repeated a school grade compared to 4.3% of children born to adult mothers (P < 0.01). Differences in sociocultural circumstances between the adolescent and adult mothers may have influenced the results. Nevertheless, children born to adolescent mothers have delayed visuomotor maturation and a low performance at school. Am. J. Hum. Biol. 9:717–723, 1997. © 1997 Wiley-Liss, Inc.     

Cerebral function in perinatally HIV-infected young adults and their HIV-uninfected sibling controls

Background:

Perinatally acquired HIV-infected (PaHIV) young adults undergo neurodevelopment in the presence of HIV infection and antiretroviral therapy, which may lead to neurocognitive (NC) impairment. Knowledge of NC function in this group is sparse and control data lacking. We compared cerebral function in young adults with PaHIV infection to aged matched HIV negative family controls.

Methods:

16–25-year-old PaHIV young adults (Group 1, n?=?33) and HIV-uninfected family controls (Group 2, n?=?14) were recruited. Cerebral function was evaluated by: a computerized battery assessing NC function (CogState^TM), International HIV Dementia Scale (IHDS) and the prospective and retrospective memory questionnaire (PRMQ). Eight cases and four controls also underwent ¹H cerebral magnetic resonance spectroscopy (¹H-MRS) scanning measuring basal ganglia (BG) metabolites. Cases and controls were compared.

Results:

Group 1 mean (SD) CD4 count; 444 (319) cells/μl, plasma HIV viral load?P>0.27 all observations). PRMQ scores were significantly higher (42 versus 35, P?=?0.02) and MRS BG inflammatory-metabolites (choline- and myo-inositol- to creatine ratios) were significantly greater in Group 1 versus Group 2 (0.83 versus 0.63, P?=?0.02 and 3.43 versus 3.03.P?=?0.09 respectively). No significant association between PRMQ score and MRS metabolites was observed (P?=?0.89).

Conclusion:

Statistically significant differences in cerebral function parameters were observed in PaHIV young adults compared to a well-matched control population. The cognitive deficit observed, in memory, rather than fine motor function, differs from the cerebral impairment often reported in HIV-infected adults.     

Absence of sustained hyperlactatemia in HIV-infected patients with risk factors for mitochondrial toxicity

BACKGROUND: The prevalence of asymptomatic hyperlactatemia among HIV-infected individuals has been reported to be 4% to 36%. This variability may reflect differences in the definition of and risk factors for hyperlactatemia and/or techniques for venous lactate collection. METHODS: We examined the prevalence of elevated venous lactate collected in accordance with Adult AIDS Clinical Trials Group (AACTG) guidelines among HIV-infected and nucleoside analogue-treated subjects with risk factors associated with hyperlactatemia. Sustained hyperlactatemia was defined as 2 consecutive levels >or=1.5 but or=2 risk factors, with 11% having >4 risk factors. The median entry venous lactate level was 1.2 mmol/L (range: 0.7-5.1 mmol/L). Two subjects had a lactate level >1.5 times the ULN: 1 with a value of 2.1 times the ULN at entry and a week 2 level of 1.2 times the ULN and a second subject with a week 2 value of 1.9 times the ULN but an entry level of 1.4 times the ULN. The latter subject developed symptomatic lactic acidosis 3 weeks following study discontinuation. CONCLUSIONS: Sustained asymptomatic hyperlactatemia among subjects with risk factors associated with hyperlactatemia was not observed when venous lactate was measured in a standardized fashion. One case of hyperlactatemia that evolved into symptomatic lactic acidosis was diagnosed soon after the completion of the study, however. Our findings indicate that asymptomatic hyperlactatemia is either very rare or an artifact of collection technique.     

Body composition changes during lactation in HIV-infected and HIV-uninfected South African women

BACKGROUND: The nutritional consequences of HIV infection in lactating women are unknown. OBJECTIVE: To measure the body composition of South African lactating women in relation to HIV status. METHODS: Fat-free mass (FFM) and fat mass (FM) using bioimpedance spectrometry (BIS) and anthropometric measurements were obtained at 8 and 24 weeks postpartum in 92 HIV-infected (HIVpos) and 50 HIV-uninfected (HIVneg) lactating mothers. RESULTS: At 8 weeks, HIVpos and HIVneg mothers were not significantly different in height (159.7 vs. 158.9 cm), weight (62.7 vs. 63.9 kg), body mass index (BMI; 24.6 vs. 25.3 kg/m), FFM (40.7 vs. 42.8 kg), or FM (21.6 vs. 22.0 kg), respectively. In HIVpos women, the median CD4 count was 621 (range: 101-1585) cells/muL; 95% had CD4 counts >200 cells/muL. Between 8 and 24 weeks, HIVpos mothers had a mean weight loss of 1.4 kg in contrast to a 0.4-kg weight gain in HIVneg mothers (P < 0.01). There were no significant group differences with regard to change in FFM (0.3 vs. 0.1 kg; P = 0.9) and FM (-1.5 vs. -0.3 kg; P = 0.2). CONCLUSION: HIVpos South African breast-feeding mothers without severe immune suppression lost weight and subcutaneous fat between 8 and 24 weeks postpartum, whereas HIVneg mothers gained weight. FFM was maintained postpartum in HIVpos and HIVneg mothers.