Predictors of attempted suicide among youth living with perinatal HIV infection and perinatal HIV exposed uninfected counterparts

Abstract Background Perinatal HIV transmission has dramatically decreased with combination antiretroviral (ARV) regimens, but complications among HIV-exposed uninfected (HEU) children, such as microcephaly, warrant ongoing surveillance. Methods We evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a prospective cohort study conducted by the PHACS network at 22 US sites. Microcephaly was defined using 2000 CDC Growth z-scores for head circumference (HC) measured at 6–36 months of age (z-score <−2) and using Nellhaus standards (<2nd percentile) after age 3 (“SMARTT” criteria), or using Nellhaus standards across all ages. Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero ARV exposure and microcephaly status, adjusted for potential confounders. Sensitivity analyses were conducted. Neurodevelopmental functioning was compared between HEU children with vs. without microcephaly. Results Among 3055 SMARTT participants enrolled as of April 2017 with a HC measurement over 5.1 years median follow-up (IQR = 3.0, 7.2), 159 (5.2%, 95% CI: 4.4–6.1%) had microcephaly identified by Nellhaus criteria and 70 (2.3%, 95% CI: 1.8–2.9%) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4.7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (aRR=2.02, 95% CI: 1.16, 3.51) and SMARTT criteria (adjusted RR = 2.56, 95% CI: 1.22, 5.37). These associations were more pronounced among children exposed to combination regimens of efavirenz which included zidovudine+lamivudine than those including tenofovir+emtricitabine (Figure 1). Associations of microcephaly with efavirenz persisted in several sensitivity analyses (Figure 2). Protective associations were observed for darunavir exposure (aRR = 0.50; 95% CI: 0.24, 1.00). HEU children with microcephaly had lower mean scores on neurodevelopmental assessments at ages 1 and 5 years and higher prevalence of impairment than those without microcephaly. Conclusion Efavirenz exposure during pregnancy was associated with a higher risk of microcephaly in infancy and childhood. These findings may support identification of alternatives to efavirenz as part of first-line ARV therapy. Disclosures All authors: No reported disclosures.

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Evidence of Impact of Maternal HIV Infection on Immunoglobulin Levels in HIV-Exposed Uninfected Children

AIDS Research and Human Retroviruses ◽

10.1089/aid.2009.0241 ◽

2010 ◽

Vol 26 (9) ◽

pp. 967-975 ◽

Cited By ~ 23

Author(s):

Madeleine Bunders ◽

Lucy Pembrey ◽

Taco Kuijpers ◽

Marie-Louise Newell

Keyword(s):

Hiv Infection ◽

Maternal Hiv ◽

Maternal Hiv Infection ◽

Hiv Exposed ◽

Evidence Of Impact ◽

Immunoglobulin Levels ◽

Exposed Uninfected

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Natural Resistance to HIV Infection: Lessons Learned from HIV‐Exposed Uninfected Individuals

The Journal of Infectious Diseases ◽

10.1086/655973 ◽

2010 ◽

Vol 202 (S3) ◽

pp. S345-S350 ◽

Cited By ~ 21

Author(s):

Gianfranco Pancino ◽

Asier Saez‐Cirion ◽

Daniel Scott‐Algara ◽

Pascale Paul

Keyword(s):

Hiv Infection ◽

Lessons Learned ◽

Natural Resistance ◽

Hiv Exposed ◽

Exposed Uninfected

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Early Weaning of HIV-Exposed Uninfected Infants and Risk of Serious Gastroenteritis: Findings from Two Perinatal HIV Prevention Trials in Kampala, Uganda

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/qai.0b013e3181bdf68e ◽

2010 ◽

Vol 53 (1) ◽

pp. 20-27 ◽

Cited By ~ 40

Author(s):

Carolyne Onyango-Makumbi ◽

Danstan Bagenda ◽

Antony Mwatha ◽

Saad B Omer ◽

Philippa Musoke ◽

...

Keyword(s):

Hiv Prevention ◽

Early Weaning ◽

Perinatal Hiv ◽

Prevention Trials ◽

Hiv Exposed ◽

Perinatal Hiv Prevention ◽

Exposed Uninfected

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Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort

10.1101/2020.05.03.20089383 ◽

2020 ◽

Author(s):

Tatum Sevenoaks ◽

Catherine J. Wedderburn ◽

Kirsten A. Donald ◽

Whitney Barnett ◽

Heather J. Zar ◽

...

Keyword(s):

Immune System ◽

Hiv Infection ◽

Birth Cohort ◽

Inflammatory Markers ◽

Gm Csf ◽

Ifn Γ ◽

Hiv Exposed ◽

Exposed Uninfected ◽

Serum Inflammatory Markers

ABSTRACTHIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in HIV-infected vs. uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother-child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ≈26 week’s gestation (n=77 HIV-infected mothers; n=190 HIV-uninfected mothers), at 6-10 weeks (n=63 HEU infants and n=159 HU infants) and at 24-28 months (n=77 HEU children and n=190 HU children). Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24-28 months. After correcting for multiple comparisons, HIV-infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26 weeks gestation (GM-CSF and MMP9, p<0.05) and HEU children at 6-10 weeks (IFN-γ and IL-1β, p<0.01), and at 24-28 months (IFN-γ, IL-1β, IL-2 and IL-4, p<0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6-10 weeks, inflammatory markers (GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1P, IL-2, IL-4, IL-6 and NGAL, all p<0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research.

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Placental Transfer of Respiratory Syncytial Virus Antibody Among HIV-Exposed, Uninfected Infants

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piz056 ◽

2019 ◽

Vol 9 (3) ◽

pp. 349-356

Author(s):

Sweta M Patel ◽

Sabelle Jallow ◽

Sefelani Boiditswe ◽

Shabir A Madhi ◽

Kristen A Feemster ◽

...

Keyword(s):

Hiv Infection ◽

Neutralizing Antibodies ◽

Placental Transfer ◽

Immunodeficiency Virus ◽

Maternal Hiv ◽

Maternal Hiv Infection ◽

Syncytial Virus ◽

Hiv Exposed ◽

Antibody Levels ◽

Exposed Uninfected

Abstract Background Maternal human immunodeficiency virus (HIV) infection is associated with lower placental transfer of antibodies specific to several childhood pathogens. Our objective for this study was to evaluate the effect of maternal HIV infection on the placental transfer of respiratory syncytial virus (RSV)-neutralizing antibodies. Methods We conducted a cross-sectional study of mothers and their newborn infants at a tertiary hospital in Gaborone, Botswana, between March 2015 and December 2015. We measured serum RSV antibody levels by using a microneutralization assay. We used multivariable linear regression to evaluate the effect of maternal HIV infection on maternal RSV antibody levels, placental transfer of RSV antibodies, and newborn RSV antibody levels. Results Of 316 mothers, 154 (49%) were infected with HIV. The placental transfer ratios for RSV antibodies to HIV-exposed, uninfected (HEU) and HIV-unexposed, uninfected infants were 1.02 and 1.15, respectively. The geometric mean titer (95% confidence interval) of RSV-neutralizing antibodies was 2657 (2251–3136) among HEU newborns and 2911 (2543–3331) among HIV-unexposed, uninfected newborns. In multivariable analyses, maternal HIV infection was associated with lower placental transfer of RSV antibodies (P = .02) and a lower level of RSV antibodies among newborns (P = .002). Among HEU newborns, higher birth weight (P = .004) and an undetectable maternal antenatal viral load (P = .01) were associated with more effective placental transfer of RSV antibodies. Conclusions Maternal human immunodeficiency virus (HIV) infection is associated with lower mother-to-fetus transfer of serum RSV-neutralizing antibodies. HEU infants should be prioritized for preventive interventions for RSV. Maternal viral suppression through combination antiretroviral therapy has the potential to improve immunity to RSV among HIV-exposed infants.

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