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Few studies have compared clinical outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) infants in the current scenario of universal and lifelong maternal antiretroviral therapy (ART). HIV-uninfected and HIV-infected Malawian women receiving ART and their breastfed infants were followed for 12 months postpartum, analyzing the rates of infectious and noninfectious events and assessing infant growth at 6 weeks, 6 months, and 12 months. The cohorts included 227 mothers (70 HIV-negative, 157 HIV-positive) and 235 infants (72 HUU, 163 HEU). No maternal or infant deaths occurred during follow-up. HIV-negative women were less likely to complete follow-up (48.6% versus 91.1%). Mothers with and without HIV had similar rates of both infectious and noninfectious events per person-month. Infants who were HEU, compared with HUU, had higher rates of events of any type, lower respiratory tract infections (LRTI), and noninfectious events. HEU had lower body mass index (BMI) at 6 weeks but did not differ from HUU in all anthropometric measures at 6 and 12 months; in growth between 6 weeks and 12 months; and in occurrence of stunting, underweight, and wasting at 6 weeks, 6 months, and 12 months. During the first year of life, infants who were HEU, compared with HUU, showed a transiently lower BMI and an increased risk of LRTI.

Background The evaluation of immunological status with respect to vaccine-preventable infectious diseases allows to identify populations with suboptimal protection. HIV-exposed infants, even if not infected with HIV, have higher morbidity and mortality in comparison to their unexposed counterparts, and even if the underlying mechanisms have not been clearly elucidated, dysfunctional immune responses might be involved. The aim of this study was to evaluate post-vaccination immune responses in two groups of infants (HIV-exposed and HIV-unexposed) living in the area of Blantyre, Malawi, measuring IgG levels against Haemophilus Influenzae type B (HiB), Hepatitis B (HBV), and Streptococcus pneumoniae (PCP). Methods Sixty-two infants, 49 HIV-exposed, uninfected (HEU), born to women living with HIV, and 13 HIV-unexposed, uninfected (HUU), born to HIV-negative mothers, were included in the study. The infants were visited monthly, from birth to 12 months, and blood samples were collected at 6 months. Anti-HiB, -HBV and -PCP vaccines are administered in Malawi at 6, 10, and 14 weeks of life. The antibody responses to the vaccines were determined by ELISA tests. Results The geometric mean concentrations (GMCs) of anti-HiB, anti-HBs and anti-PCP antibodies were not different between the two groups. The proportion of infants with protective levels (> 0.15 mg/l) versus HiB was lower (although not significantly) in HEU in comparison to HUU infants (81.6% vs 100%, p = 0.095). There was no significant difference between the two groups in the proportion of infants with protective antibody levels against HBV or PCP, although this proportion was lower than expected in both groups, varying from 81.6–84%. Overall, only 61.3% of the infants showed protective levels against all three vaccine antigens. Conclusions The humoral response after vaccination was similar in HEU and HUU infants. A disturbingly high proportion of infants without protective antibody levels against HBV and PCP in both groups of infants and against HiB in HEU infants was observed.

Background Post-partum loss to follow-up and lack of early HIV infant diagnosis (EID) can significantly affect the efficiency of programs for the prevention of mother-to-child transmission. Methods In a prospective observational study 167 women were enrolled at week 36 of gestation and followed with their infants up to one year after delivery. Retention was defined as the proportion of women who attended the 12 months visit and EID as an HIV PCR test performed within 2 months. Determinants for retention and EID were assessed in univariate analyses and in multivariable logistic regression models. Results Women lost to follow-up (24/167 or 14.4%) had a shorter duration of antiretroviral therapy (ART) at enrolment in comparison to women retained in care ( p = 0.025). Lack of EID (occurring in 18.9% of the cases) was directly correlated, although not significantly, with a history of child death ( p = 0.071), a higher educational level ( p = 0.083), and female infant gender ( p = 0.064). Conclusions Longer duration of ART at enrolment significantly predicted a better post-partum retention, suggesting that specific counselling interventions should be targeted to recent ART initiators. A low proportion of infants did not receive an EID, but predictive factors were difficult to identify.

Background In sub-Saharan African countries Epstein Barr virus (EBV) infection occurs in early childhood. We aim to investigate the factors associated with EBV acquisition and the impact of EBV infection on the humoral response to HBV vaccination in infants born from HIV-positive, antiretroviral-treated mothers in Malawi. Methods A total of 149 HIV-exposed infants were included in this longitudinal study. EBV anti-VCA IgG were measured using an ELISA assay. The EBV seroconversion was correlated with the maternal viro-immunological conditions, with infant growth and immunological vulnerability, and with the humoral response to the HBV vaccine. Results No infant was EBV-positive at 6 months (n. 52 tested). More than a third of infants (49/115 or 42.6 %) on study beyond 6 months seroconverted at 12 months. At 24 months, out of 66 tested infants, only 13 remained EBV-uninfected, while 53 (80.3 %) acquired EBV infection, rising the total proportion of EBV seroconversion to 88.7 % (102/115 infants). EBV seroconversion was significantly associated with a low maternal educational status but had no impact on infant growth or vulnerability to infections. Reduced HBsAb levels and accelerated waning of antibodies were associated with early EBV seroconversion. Conclusions We found a heterogeneous timing of acquisition of EBV with the majority of infants born from HIV + mothers acquiring infection after 6 months. Anti-HBs levels were lower and appeared to wane faster in infants acquiring EBV infection.

Transplacental passage of IgGs is impaired in HIV + pregnant women, possibly determining an inadequate immunological protection in their children. We aimed to determine the impact of maternal immunological IgG profile and immunoactivation status on the efficiency of transplacental passage of IgG subclasses in HIV + mothers. 16 mother/infants pairs were studied in Malawi. Mothers received antiretroviral therapy (ART) from the third trimester of pregnancy. Determinations of pre-ART levels of maternal sCD14, of IgG subclasses in mothers at delivery and in their 1-month-old infants, were performed using commercial ELISA kits. At delivery, after a median of 10 weeks of ART, 12/16 mothers were hypergammaglobulinemic, with IgG levels (20.5 mg/ml, 95% CI:18.8–26.8) directly correlated to the plasmatic levels of sCD14 (r = 0.640, p = 0.014). IgG1 levels (17.9 mg/ml) accounted for 82% of IgG, IgG3 and IgG4 levels were in the normal range. A profound deficit of IgG2 was observed both in mothers (0.60 mg/ml) and in infants (0.14 mg/ml). Placental transfer ratio (range 0.16–0.42) did not show a selective impairment between the different IgG subclasses. The transplacental passage of all IgG subclasses was decreased in the presence of maternal IgG over 16 mg/ml (significantly for IgG1, p = 0.031) and of high levels of sCD14 (p = 0.063). Transplacental passage was reduced for all IgG subclasses and inversely correlated to high levels of maternal IgGs and to the degree of immunoactivation. The profound depression of IgG2 in mothers suggests that IgG2 neonatal levels mostly reflect the maternal deficit rather than a selective impairment of IgG2 transfer.

Background HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life. Methods Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally. Results Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 μg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018). Conclusion We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings.

The aim of this study was to assess the immune response to HBV vaccine in HIV-exposed infants and to correlate it to HBV infection acquisition. Protective anti-HBs levels (>10 mIU/mL) were found in 54/58 (93.2%) infants at 6 months, 126/144 (87.5%) at 12 months and 141/176 (80.1%) children at 24 months. HBV infection (seven children were HBsAg + at Month 24) occurred also in the presence of levels above 10 mIU/mL. Our findings indicate limited impact of HIV exposure on anti-HBV immune response, but suggest that levels >10 mIU/mL may be required to confer protection in this context.