Maternal Diarrhea and Antibiotic Use are Associated with Increased Risk of Diarrhea among HIV-Exposed, Uninfected Infants in Kenya

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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Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of highly active anti-retroviral therapy

10.1101/2021.07.26.21261143 ◽

2021 ◽

Author(s):

Louise Afran ◽

Kondwani C Jambo ◽

Wilfred Nedi ◽

David J.C Miles ◽

Anmol Kiran ◽

...

Keyword(s):

B Cell ◽

Sub Saharan Africa ◽

Haemophilus Influenzae Type ◽

Cell Phenotype ◽

Bacterial Disease ◽

Enzymatic Function ◽

Increased Risk ◽

Hiv Exposure ◽

Hiv Exposed ◽

Exposed Uninfected

HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in Sub Saharan Africa and are highly particularly susceptible to disease caused by encapsulated bacteria in the first year of life. The mechanism of this increased risk is still poorly understood and we therefore, investigated if HIV exposure dysregulates HEU infant immunity and if this is amplified by human herpes infection (HHV). Here, we compared monocyte enzymatic function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HUU infants. We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HUU infants. There was no difference in the prevalence of HHV infection between HEU and HUU infants. Our findings suggest that even in the era of ART-mediated viral suppression, HIV exposure dysregulates monocyte and B cell function during a vulnerable period of immune maturation in infancy. This may contribute to the high rates of bacterial disease and pneumonia in HEU infants.

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Increased Risk of Serious Bacterial Infections Due to Maternal Immunosuppression in HIV-Exposed Uninfected Infants in a European Country

Clinical Infectious Diseases ◽

10.1093/cid/ciu586 ◽

2014 ◽

Vol 59 (9) ◽

pp. 1332-1345 ◽

Cited By ~ 46

Author(s):

C. Taron-Brocard ◽

J. Le Chenadec ◽

A. Faye ◽

C. Dollfus ◽

T. Goetghebuer ◽

...

Keyword(s):

European Country ◽

Bacterial Infections ◽

Increased Risk ◽

Serious Bacterial Infections ◽

Hiv Exposed ◽

Exposed Uninfected

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Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15–18 Months of Age Among Human Immunodeficiency Virus (HIV)–infected, HIV-exposed–uninfected, and HIV-unexposed Children

Clinical Infectious Diseases ◽

10.1093/cid/ciy964 ◽

2018 ◽

Vol 69 (4) ◽

pp. 687-696 ◽

Cited By ~ 1

Author(s):

Eleonora A M L Mutsaerts ◽

Marta C Nunes ◽

Martijn N van Rijswijk ◽

Kerstin Klipstein-Grobusch ◽

Kennedy Otwombe ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Geometric Mean ◽

Treatment Interruption ◽

Enzyme Linked Immunosorbent Assay ◽

Increased Risk ◽

Immunodeficiency Virus ◽

Antibody Titers ◽

Measles Vaccination ◽

Hiv Exposed ◽

Exposed Uninfected

AbstractBackgroundHuman immunodeficiency virus (HIV)–infected and HIV-exposed–uninfected (HEU) children may be at increased risk of measles infection due to waning of immunity following vaccination. We evaluated persistence of antibodies to measles vaccination at 4.5 years of age in HIV-unexposed, HEU, and HIV-infected children with CD4+ ≥25% previously randomized to immediate antiretroviral therapy (ART) interrupted at 12 months (HIV/Immed-ART-12), 24 months (HIV/Immed-ART-24), or when clinically/immunologically indicated (HIV/Def-ART). The HIV/Def-ART group initiated ART by median 5.8 (interquartile range, 4.4–10.3) months of age.MethodsIn this study, HIV-unexposed (n = 95), HEU (n = 84), HIV/Immed-ART-12 (n = 70), HIV/Immed-ART-24 (n = 70), and HIV/Def-ART (n = 62) children were scheduled to receive measles vaccination at age 9 and 15–18 months. Antimeasles serum immunoglobulin G titers were quantified using enzyme-linked immunosorbent assay at 4.5 years.ResultsCompared with HIV-unexposed children (2860 mIU/mL), measles antibody geometric mean titers (GMTs) were significantly lower in both HIV/Immed-ART-12 (571; P < .001) and HIV/Immed-ART-24 (1136; P < .001) but similar in the HIV/Def-ART (2777) and HEU (3242) groups. Furthermore, compared with HIV-unexposed, antibody titers ≥330 mIU/mL (ie, presumed serocorrelate for protection; 99%) were also significantly lower in HIV/Immed-ART-12 (70%; P < .001) and HIV/Immed-ART-24 (83%; P < .001) but similar in the HIV/Def-ART (90%) and HEU (98%) groups.ConclusionsHIV-infected children in whom ART was interrupted at either 12 or 24 months had lower GMTs and lower proportions with seroprotective titers than HIV-unexposed children, indicating a potential downside of ART treatment interruption.Clinical Trials RegistrationNCT00099658 and NCT00102960.

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HIV-Exposed Uninfected Infants are at Increased Risk for Severe Infections in the First Year of Life

Journal of Tropical Pediatrics ◽

10.1093/tropej/fms019 ◽

2012 ◽

Vol 58 (6) ◽

pp. 505-508 ◽

Cited By ~ 86

Author(s):

A. Slogrove ◽

B. Reikie ◽

S. Naidoo ◽

C. De Beer ◽

K. Ho ◽

...

Keyword(s):

First Year ◽

Increased Risk ◽

Severe Infections ◽

Hiv Exposed ◽

First Year Of Life ◽

Exposed Uninfected

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Children From Developing Countries at Increased Risk Because of Parental Under-reporting of Antibiotic Use

AAP Grand Rounds ◽

10.1542/gr.2-1-7-a ◽

1999 ◽

Vol 2 (1) ◽

pp. 7-8

Author(s):

K. Olness

Keyword(s):

Developing Countries ◽

Antibiotic Use ◽

Increased Risk

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Faculty Opinions recommendation of Neurodevelopment and in utero antiretroviral exposure of HIV-exposed uninfected infants.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2137011.1737121 ◽

2010 ◽

Author(s):

William Shearer ◽

Madhu Narra

Keyword(s):

In Utero ◽

Hiv Exposed ◽

Exposed Uninfected

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304. Predictors of mortality in carbapenem-resistant Enterobacteriales bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.347 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S150-S150

Author(s):

Michael R Hovan ◽

Vanessa Cedarbaum ◽

Thomas Kirn ◽

Thomas Kirn

Keyword(s):

Mortality Rate ◽

Healthcare Facility ◽

Antibiotic Use ◽

The United States ◽

Empiric Therapy ◽

Carbapenem Resistant ◽

Increased Risk ◽

Threat Level ◽

Infection Source ◽

Microbiological Data

Abstract Background Carbapenem-Resistant Enterobacteriales (CRE) bacteremia is associated with significant morbidity and mortality. CRE were assigned a threat level of “urgent” in the 2019 CDC report on antibiotic resistance in the United States. We attempted to identify predictors of 30-day mortality in patients with CRE bacteremia. Methods We performed a chart review of 146 patients with CRE bacteremia from January 2010 - July 2019. CRE was defined using the current CDC definition. Electronic medical records were reviewed to obtain clinical characteristics and outcomes including prior antibiotic use, comorbidities, prior location, treatment, hospital course, microbiological data and outcomes including in-hospital mortality. Results Of 146 patients included for analysis, the overall 30-day mortality rate was 36.3%. Patients admitted from a healthcare facility including outside hospitals, rehab, nursing homes, and LTACs had a 49.1% (29/59) 30-day mortality rate compared to 27.5% (24/87) for those admitted from home (RR=1.78, 95% CI 1.16–2.73, p=.0082). Patients with a Pitt bacteremia score ≥ 4 had a greater 30-day mortality rate (42.6%, 26/61) compared to those with a Pitt bacteremia score < 4 (17.6%, 15/85) (RR=2.92, 95% CI 1.40–4.16, p=.0015). Patients that received inactive empiric therapy had a 30-day mortality rate of 36% (36/100) compared to 36.9% (17/46) in those that received active empiric therapy (RR=.9741, 95% CI .6155-1.59, p=.9109). Patients with isolates determined to have a meropenem MIC ≥ 4 had a 30-day mortality rate of 40.2% (37/92) while those with an MIC < 4 had a 30-day mortality rate of 30.2% (16/53) (RR=1.33, 95% CI .8250–2.1513, p=.2408). A pulmonary source of bacteremia was associated with an increased risk of 30-day mortality (64.3%, 9/14) compared to all other sources of bacteremia (34.8%, 31/89) (RR=1.85, 95% CI 1.39–2.99, p=.0129). No other infection source was associated with an increased 30-day mortality rate. Conclusion Admission from a healthcare facility, Pitt bacteremia score ≥ 4, and pulmonary source of bacteremia were associated with increased risk of 30-day mortality. Interestingly, administration of active empiric therapy was not associated with a decreased mortality risk. Meropenem MIC was not predictive of 30-day mortality. Disclosures All Authors: No reported disclosures

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Achievements and Challenges in the Prevention of Mother-to-Child Transmission of HIV—A Retrospective Cohort Study from a Rural Hospital in Northern Tanzania

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052751 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2751

Author(s):

Sunniva Marie Nydal ◽

Yuda Munyaw ◽

Johan N. Bruun ◽

Arne Broch Brantsæter

Keyword(s):

Hiv Infections ◽

Rural Hospital ◽

Mother To Child Transmission ◽

Child Transmission ◽

Cd4 Cell Count ◽

Poor Countries ◽

Northern Tanzania ◽

Increased Risk ◽

Hiv Exposed ◽

Mother To Child

Despite the goal of eliminating new human immunodeficiency virus (HIV) infections in children, mother-to-child transmission is still common in resource-poor countries. The aims of this study were to assess the occurrence of mother-to-child transmission of HIV (MTCT) by age 18 months, risk factors for transmission, and the implementation of the national prevention of MTCT (PMTCT) program in a rural hospital in Tanzania. Data were collated from various medical registers and records. We included 172 children and 167 HIV-infected mothers. Among 88 children (51%) with adequate information, 9 (10.2%) were infected. Increased risk of MTCT was associated with late testing of the child (>2 months) [OR = 9.5 (95% CI: 1.8–49.4)], absence of antiretroviral therapy during pregnancy [OR = 9.7 (95% CI: 2.1–46.1)], and maternal CD4 cell count <200 cells/mm3 [OR = 15.3 (95% CI: 2.1–111)]. We were unable to determine the occurrence of MTCT transmission in 84 children (49%). The results from this study highlight that there is an urgent need for enhanced efforts to improve follow-up of HIV-exposed children, to improve documentation in registries and records, and to facilitate ease of linkage between these.

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