scholarly journals Cotrimoxazole Prophylaxis Selects for Antimicrobial Resistance in Human Immunodeficiency Virus–Exposed, Uninfected Infants

2019 ◽  
Vol 71 (11) ◽  
pp. 2869-2871 ◽  
Author(s):  
Claire D Bourke ◽  
Ceri Evans
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antimicrobial Resistance ◽  
Cotrimoxazole Prophylaxis ◽  
Immunodeficiency Virus ◽  
Exposed Uninfected

scholarly journals Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus–Exposed, Uninfected Infants

2019 ◽  
Vol 71 (11) ◽  
pp. 2858-2868 ◽  
Author(s):  
Alaric W D’Souza ◽  
Eshia Moodley-Govender ◽  
Bertram Berla ◽  
Tejas Kelkar ◽  
Bin Wang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Gut Microbiome ◽  
Cotrimoxazole Prophylaxis ◽  
Β Diversity ◽  
Α Diversity ◽  
Immunodeficiency Virus ◽  
Functional Pathway ◽  
Exposed Uninfected

Abstract Background Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)–exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. Methods We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. Results Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2–1.2] and 6-month mean, 0.85 [95% CI, .1–1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, −0.11 [95% CI, −.15 to −.077]), functional taxonomic (mean, −0.050 [95% CI, −.084 to −.017]), and resistance gene (mean, −0.13 [95% CI, −.17 to −.099]) β-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. Conclusions Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance.

scholarly journals A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus–Exposed Uninfected Infants

2020 ◽  
Author(s):  
Sylvia M LaCourse ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
A J Warr ◽  
Elizabeth Maleche-Obimbo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
High Risk ◽  
Adverse Events ◽  
Controlled Trial ◽  
Preventive Therapy ◽  
Infection Prevalence ◽  
Mycobacterium Tuberculosis Infection ◽  
Immunodeficiency Virus ◽  
Exposed Uninfected

Abstract Background Human immunodeficiency virus (HIV)–exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection. Methods We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-γ release assay (QuantiFERON-TB Gold Plus) and/or tuberculin skin test (TST, added 6 months after first participant exit). Results Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287/298), and 88.9% (265/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28/265); 7.6% (10/132) in the INH arm and 13.5% (18/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24–1.14]; P = .11]), and driven primarily by TST positivity (8.6% [8/93] in INH and 18.1% [17/94] in no INH; relative risk, 0.48 [95% CI, .22–1.05]; P = .07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21/150] vs no INH, 10.7% [16/150]; P = .38), with no INH-related adverse events. Conclusions Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted. Clinical Trials Registration NCT02613169.

scholarly journals Age-Related Changes in Expression of CXCR4 and CCR5 on Peripheral Blood Leukocytes from Uninfected Infants Born to Human Immunodeficiency Virus Type 1-Infected Mothers

2004 ◽  
Vol 11 (1) ◽  
pp. 229-234 ◽  
Author(s):  
Sharon Shalekoff ◽  
Glenda E. Gray ◽  
Caroline T. Tiemessen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cord Blood ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Cross Sectional ◽  
Age Related ◽  
Immunodeficiency Virus ◽  
Sectional Analysis ◽  
Exposed Uninfected

ABSTRACT Cross-sectional analysis of human immunodeficiency virus-exposed, uninfected infants revealed high proportions of CXCR4-expressing cells in their cord blood, which declined at 4.5 months and increased between 9 and 15 months to levels approaching those of uninfected adults. Proportions of CCR5-expressing cells, however, were very low in cord blood and subsequently increased with age.

scholarly journals Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus–infected and Exposed, Uninfected Youth

2019 ◽  
Vol 69 (7) ◽  
pp. 1183-1191 ◽  
Author(s):  
Anna-Barbara Moscicki ◽  
Brad Karalius ◽  
Katherine Tassiopoulos ◽  
Tzy-Jyun Yao ◽  
Denise L Jacobson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cohort Study ◽  
Human Papillomavirus ◽  
Pediatric Hiv ◽  
Quadrivalent Vaccine ◽  
Sexually Active ◽  
Abnormal Cytology ◽  
Immunodeficiency Virus ◽  
Antibody Titers ◽  
Exposed Uninfected

AbstractBackgroundPersons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth.MethodsThis is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts.ResultsSeroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively.ConclusionAntibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.

scholarly journals Rates of Hospitalization and Infection-Related Hospitalization Among Human Immunodeficiency Virus (HIV)–Exposed Uninfected Children Compared to HIV-Unexposed Uninfected Children in the United States, 2007–2016

2019 ◽  
Vol 71 (2) ◽  
pp. 332-339
Author(s):  
Sarah M Labuda ◽  
Yanling Huo ◽  
Deborah Kacanek ◽  
Kunjal Patel ◽  
Krista Huybrechts ◽  
...  
Keyword(s):  
United States ◽  
Human Immunodeficiency Virus ◽  
Poisson Regression ◽  
The United States ◽  
Hiv Disease ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Maternal Hiv ◽  
Hiv Exposed ◽  
Exposed Uninfected

Abstract Background Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)–exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease–related factors during pregnancy with risk of child hospitalization. Methods HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006–2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization. Results A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization. Conclusions Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

Immunogenicity and Safety of an Early Measles Vaccination Schedule at 6 and 12 Months of Age in Human Immunodeficiency Virus (HIV)–Unexposed and HIV-Exposed, Uninfected South African Children

2019 ◽  
Vol 220 (9) ◽  
pp. 1529-1538 ◽  
Author(s):  
Eleonora A M L Mutsaerts ◽  
Marta C Nunes ◽  
Sutika Bhikha ◽  
Benit T Ikulinda ◽  
Welekazi Boyce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Vaccine Dose ◽  
Vaccination Schedule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Measles Vaccine ◽  
Immunodeficiency Virus ◽  
Measles Vaccination ◽  
Hiv Exposed ◽  
Vaccine Availability ◽  
Exposed Uninfected

Abstract Background Measles morbidity and mortality rates are greatest in children <12 months old, with increased susceptibility in human immunodeficiency virus (HIV)–exposed children. We evaluated the immunogenicity and safety of an early 2-dose measles vaccine regimen administered at 6 and 12 months of age in South Africa. Methods HIV-unexposed (HU) (n = 212) and HIV-exposed, uninfected (HEU) (n = 71) children received measles vaccination (CAM-70) at 6 and 12 months of age. Measles immunoglobulin G titers were measured by means of enzyme-linked immunosorbent assay before and 1 month after each vaccine dose. Results The majority of children (88.2% HU and 95.8% HEU; P = .04) were seronegative (<150 mIU/mL) to measles at 4.2 months of age. This was particularly evident among infants of mothers born from 1992 onwards (year of public nationwide measles vaccine availability). One month after the first measles vaccine, 42.3% of HU and 46.4% of HEU children were seropositive (≥330 mIU/mL). After the second dose, the proportion seropositive increased to 99.0% in HU and 95.3% in HEU children. Safety profiles were similar between HU and HEU children. Conclusions Early 2-dose measles vaccination at 6 and 12 months of age was safe and induced antibody responses in HU and HEU children, which could partly offset the early loss of maternally derived antibodies in infants born to predominantly measles-vaccinated mothers. Clinical Trials Registration NCT03330171

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