Uninfected Infants Research Articles

Undernutrition of HEU infants in their first 1000 days of life: A case in the urban-low resource setting of Mukuru Slum, Nairobi, Kenya

BackgroundAccording to the Lancet, the successful chemoprophylaxis and the introduction of lifelong antiretroviral therapy programs to eliminate mother to child transmission of HIV has promoted the rise in number of HIV exposed uninfected (HEU) infants. In resource limited settings, these infants are at an increased risk of undernutrition due to risk factors such as low birth weight, food insecurity, household composition, income and improper feeding patterns. As several other studies have suggested, the risk factors vary from one setting to another. This paper delved into reviewing the predisposing undernutrition factors in relation to HIV exposure among infants within the low resource urban setting of Mukuru Slum, in Nairobi, Kenya. MethodsA retrospective cohort study was performed on 160 mother/guardian-child pairs in Mukuru Slum, Nairobi, Kenya. Growth charts of the HIV exposed uninfected infants were studied against a control group of HIV unexposed uninfected infants (HUU). Interviews to collect information on socio economic status, household composition, HIV exposure, infant feeding practices and food insecurity related challenges were done. Data was analyzed using IBM SPSS version 20 and WHO anthroplus software. Descriptive statistics as well as Chi square, t-tests and multivariate analysis was done. ResultsStunting among the HIV exposed uninfected infants was the most common form of undernutrition. 38.9% of the HEU infants were severely stunted (LFAZ), while 5.6% of them were severely wasted (WFLZ), while 24.4% of them were severely underweight. The mean birth weights of the HEU infants (2.953kg) was lower than the HUU (3.195kg). HIV exposure was associated with lower Weight for Length Z score (WFLZ), Weight for Age Z score (WFAZ), Length for Age Z score (LFAZ), BMI for Age Z score (BAZ) and Middle Upper Arm Circumference Z score (MUACZ) (p<0.001). HEU infants were more likely to live in households with lesser number of adults (p=0.016) and higher number of children (p<0.001) as compared to the HUU. Although exclusive breastfeeding was upheld among all infants, the HEU were more likely to rely on Food by Prescription supplements (p<0.001) to meet their daily energy needs. Households with HEU infants were, however, less likely to receive food (p=0.041). Overall the largest effect sizes on undernutrition of all infants was found to be affected by the age of children (ηp2=0.439; p<0.001), sex (ηp2=0.135; p=0.001), HIV exposure (ηp2=0.351; p<0.001) and food aid (ηp2=0.083; p=0.021). ConclusionThis study concluded that, HIV exposed uninfected infants in Mukuru were faced with a high undernutrition risk that was associated with HIV exposure, household composition, food aid and use of food by prescription supplements. These factors provide an insight when managing undernutrition among such infants in other resource limited settings. This study recommends future operational studies to inform HIV programs on exact ways to eliminate undernutrition among the rising number of HEU infants.

Investment Long Overdue in Primary Studies of HIV-exposed Uninfected Infant Infectious Morbidity

Investment Long Overdue in Primary Studies of HIV-exposed Uninfected Infant Infectious Morbidity

Third Trimester Vitamin D Status Is Associated With Birth Outcomes and Linear Growth of HIV-Exposed Uninfected Infants in the United States.

Vitamin D status in pregnancy may influence the risk of prematurity, birth size, and child postnatal growth, but few studies have examined the relationship among pregnant women living with HIV. We conducted a prospective cohort study of 257 HIV-infected mothers and their HIV-exposed uninfected infants who were enrolled in the 2009-2011 nutrition substudy of the Surveillance Monitoring for ART Toxicities (SMARTT) study. HIV-infected pregnant women had serum 25-hydroxyvitamin D (25(OH)D) assessed in the third trimester of pregnancy, and their infants' growth and neurodevelopment were evaluated at birth and approximately 1 year of age. The mean third trimester serum 25(OH)D concentration was 35.4 ± 14.2 ng/mL with 15% of women classified as vitamin D deficient (<20 ng/mL) and 21% as insufficient (20-30 ng/mL). In multivariable models, third trimester vitamin D deficiency and insufficiency were associated with -273 g [95% confidence interval (CI): -450 to -97] and -203 g (95% CI: -370 to -35) lower birth weights compared with vitamin D sufficient women, respectively. Maternal vitamin D deficiency was also associated with shorter gestation (mean difference -0.65 weeks; 95% CI: -1.22 to -0.08) and lower infant length-for-age z-scores at 1 year of age (mean difference: -0.65; 95% CI: -1.18 to -0.13). We found no association of vitamin D status with infant neurodevelopment at 1 year of age. Third trimester maternal vitamin D deficiency was associated with lower birth weight, shorter length of gestation, and reduced infant linear growth. Studies and trials of vitamin D supplementation in pregnancy for women living with HIV are warranted.

Re: “Investment Long Overdue in Primary Studies of HIV-exposed Uninfected Infant Infectious Morbidity”

Re: “Investment Long Overdue in Primary Studies of HIV-exposed Uninfected Infant Infectious Morbidity”

Breastfeeding Support Offered at Delivery is Associated with Higher Prevalence of Exclusive Breastfeeding at 6 Weeks Postpartum Among HIV Exposed Infants: A Cross-Sectional Analysis.

Objective HIV-exposed uninfected infants are almost twice as likely to die compared to infants born to HIV-uninfected women. HIV-exposed uninfected children whose mothers are on ART and who are breastfed have the lowest risk of dying by 24months of age. Interventions to improve breastfeeding among HIV-infected mothers are needed. We aimed to assess the association between support/counseling provided by healthcare workers following delivery and the rate of exclusive breastfeeding (EBF) at 6-week postpartum. Methods This is a secondary analysis of data collected as part of a trial to evaluate the effect of conditional cash transfers on retention in and uptake of PMTCT services. Between April 2013 and August 2014, newly diagnosed HIV-infected women, ≤ 32weeks pregnant, registering for antenatal care (ANC), in 89 clinics in Kinshasa, Democratic Republic of Congo, were recruited and followed through 6 weeks postpartum. At 6-week, participants were asked if they had given anything other than breastmilk to their infant in the 24h preceding the interview (No = EBF) and whether a nurse or a doctor talked to them about breastfeeding after they gave birth (YES = received breastfeeding support/counseling). Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) measuring the strength of the association between EBF and receiving breastfeeding support/counseling by a healthcare provider following delivery. Results Of 433 women enrolled, 328 attended a 6-week postpartum visit including 320 (97%) with complete information on EBF. Of those 320, 202 (63%) reported giving nothing other than breastmilk to their infant in the previous 24h; 252 (79%) reported that a healthcare provider came to talk to them about breastfeeding following delivery. Mothers who reported receiveing breastfeeding support/counseling from a healthcare provider were more likely to exclusively breastfeed compared to those who did not (69% vs. 38%, OR 3.74; 95% CI 2.14-6.54). Adjustment for baseline sociodemographic characteristics did not change the association substantially, (adjusted OR 3.72; 95% CI 2.06-6.71). Conclusion for Practice Receipt of breastfeeding support/counseling from a healthcare provider after delivery among HIV-infected mothers in care at 6-weeks postpartum in Kinshasa almost quadrupled the odds of EBF.

Non-nucleoside reverse transcriptase inhibitor levels among HIV-exposed uninfected infants at the time of HIV PCR testing - findings from a tertiary healthcare facility in Pretoria, South Africa.

IntroductionTo date, very little programmatic data has been published regarding serial antiretroviral (ARV) levels in infants exposed to maternal treatment and/or infant prophylaxis during the first months of life. Such data provide the opportunity to describe the proportion of infants exposed to virologically suppressive levels of ARVs and to gauge adherence to the prevention of mother‐to‐child transmission of HIV (PMTCT) programme.MethodsFrom August 2014 to January 2016, HIV‐exposed infants born at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa were enrolled as part of an observational cohort study. Plasma samples from HIV‐exposed uninfected infants were obtained at birth, 6‐weeks, 10‐weeks and 14‐weeks of age and quantitative efavirenz (EFV) and nevirapine (NVP) drug level testing performed using liquid chromatography‐mass spectrometry, irrespective of maternal ARV regimen. Descriptive analysis of EFV and NVP levels in relation to self‐reported maternal and infant ARV exposure was performed. EFV levels >500 ng/mL and NVP levels >100 ng/mL were reported based on studies suggesting that trough levels above these thresholds are associated with virological suppression and PMTCT respectively.ResultsAmong 66 infants exposed to maternal EFV in utero, 29 (44%) had virologically suppressive plasma EFV levels at birth, with a median level of 1665 ng/mL (IQR: 1094 to 3673). Among infants who were exclusively breastfed at 6‐, 10‐ and 14 weeks, 13/48 (27%), 5/25 (25%) and 0/21 (0%) had virologically suppressive EFV levels. Among 64 infants whose mothers reported administering daily infant NVP at time of their 6‐week HIV PCR test, only 45 (70%) had NVP levels above the minimum prophylactic trough level.ConclusionsDuring the first 10‐weeks after delivery, a quarter of breastfed infants born to women on an EFV‐containing treatment regimen maintained virologically suppressive EFV plasma levels. This finding highlights the importance of both careful monitoring of ARV side effects and repeat HIV PCR after the first few months of life among HIV‐exposed uninfected infants. As 30% of infants had inadequate NVP plasma levels at 6‐weeks of age, adherence counselling to caregivers regarding infant prophylaxis needs to be enhanced to further reduce mother‐to‐child transmission of HIV.

Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women

The placental transfer of maternal IgG is critical for infant protection against infectious pathogens. However, factors that modulate the placental transfer of IgG remain largely undefined. HIV-infected women have impaired placental IgG transfer, presenting a unique "disruption model" to define factors that modulate placental IgG transfer. We measured the placental transfer efficiency of maternal HIV and pathogen-specific IgG in US and Malawian HIV-infected mothers and their HIV-exposed uninfected and infected infants. We examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, IgG subclass, and glycan signatures and their association with placental IgG transfer efficiency. Maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcγRIIa and FcγRIIIa, and Fc region glycan profiles were associated with placental IgG transfer efficiency. Our findings suggest that Fc region characteristics modulate the selective placental transfer of IgG, with implications for maternal vaccine design and infant health.

Comparison of Feeding Options for HIV-Exposed Infants: A Retrospective Cohort Study

To compare growth, anemia prevalence, and sickness frequency in HIV- exposed uninfected infants on different feeding modes. In this retrospective cohort study, 109 HIV-exposed uninfected infants registered at our center were categorized into three groups as per their feeding mode during first 6 months viz. exclusively breast fed (n=50), animal milk fed (n=40) and commercial infant formula fed (n=19). Their anthropometric parameters, hemoglobin and frequency of sickness at the age of 6 months were compared. There were no significant inter-group differences in the weight for age, weight for length, length for age z-scores (P=0.16, 0.37 and 0.12, respectively); proportion of infants with underweight (P=0.63), wasting (P=0.82), or stunting (P=0.82), and mean hemoglobin levels among the 3 groups at 6 month of age. Animal milk fed and formula fed infant had increased risk of sickness compared to exclusively breastfed infants (OR 2.5 and 2.49, respectively; P<0.01). In circumstances where breastfeeding is not feasible or preferred, animal milk feeding offers a viable alternative to commercial infant feeding formula in HIV exposed infants.

Reduced Transplacental Transfer of Antimalarial Antibodies in Kenyan HIV-Exposed Uninfected Infants.

BackgroundAltered neonatal immune responses may contribute to the increased morbidity observed in HIV-exposed but uninfected (HEU) infants compared with HIV-unexposed uninfected (HUU) infants. We sought to examine the effects of prenatal HIV and malaria exposure on maternal and neonatal plasma cytokine profiles and transplacental antibody transfer.MethodsForty-nine HIV+ and 50 HIV- women and their HIV-uninfected neonate pairs from Kenya were assessed. All HIV+ mothers received combination antiretroviral therapy. Maternal plasma and cord blood plasma samples at delivery were tested for 12 cytokines, total IgG, and IgG specific to 4 vaccine antigens and 14 Plasmodium falciparum antigens.ResultsHIV+ mothers had lower levels of all 12 plasma cytokines at delivery compared with HIV- mothers, but there were no differences between HEU and HUU neonates. There were no differences in the cord-to-maternal ratios (CMRs) of vaccine-specific IgG between HIV+/HEU and HIV-/HUU maternal–neonate pairs. HIV+/HEU maternal–neonate pairs had significantly lower CMRs for 3 antimalarial IgGs—merozoite surface protein 9, circumsporozoite protein, and erythrocyte binding antigen 181—which remained statistically significant after adjustment for malaria in pregnancy.ConclusionsIn a cohort of optimally treated HIV-infected pregnant women, maternal HIV infection was associated with reduced transplacental transfer of antimalarial antibodies.

Exposure of HIV-exposed uninfected infants to antiretrovirals

As various national HIV/AIDS control programmes worldwide continue to adopt WHO's option B+ approach, 1 WHOAntiretroviral drugs for treating pregnant women and preventing HIV infection in infants: recommendations for a public health approach. World Health Organization, Geneva, Switzerland2010: 1-105 Google Scholar , 2 WHOProgamme update: use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. World Health Organization, Geneva:, SwitzerlandApril, 2012 Google Scholar we will continue to have a growing population of infants who have been exposed not only to in-utero HIV infection, but also to prolonged exposure to ante-partum and post-partum antiretroviral drugs, including around 6 weeks of infant prophylaxis with nevirapine combined with triple antiretroviral exposure through breastfeeding. 3 Schouten E Midiani M Makombe S et al. Prevention of mother-to-child transmission of HIV and the health related Millennium Development Goals: time for a public health approach. Lancet. 2011; 378: 282-284 Summary Full Text Full Text PDF PubMed Scopus (195) Google Scholar Most of these infants remain free from HIV infection, and are currently referred to as HIV-exposed and uninfected. There is growing evidence that mortality is higher for these infants than for those who are HIV-unexposed and uninfected. 4 Newell M Coovadia H Cortina-Borja M et al. Mortality of infected and uninfected infants born to HIV infected mothers in Africa: a pooled analysis. Lancet. 2004; 364: 1236-1243 Summary Full Text Full Text PDF PubMed Scopus (907) Google Scholar , 5 Kuhn L Sinkala M Semrau K et al. Elevations in mortality associated with weaning persist into the second year of life among uninfected children born to HIV-infected mothers. Clin Infect Dis. 2010; 50: 437-444 Crossref PubMed Scopus (80) Google Scholar Additionally, in this age of heightened awareness of the importance of early childhood development, one major concern for parents of HIV-exposed and uninfected infants and health-care workers taking care of the family is whether these children have normal neurological development. Are we saving HIV-exposed infants from HIV infection but leaving them with higher morbidity from exposure to the virus and perhaps also exposure to the antiretroviral drugs than unexposed infants? 6 Hutchins J Potterton J Developmental delay in HIV exposed infants in Harare, Zimbabwe. Vulnerable Child Youth Stud. 2013; 9: 43-55 Crossref Scopus (22) Google Scholar Neurodevelopmental effects of ante-partum and post-partum antiretroviral exposure in HIV-exposed and uninfected children versus HIV-unexposed and uninfected children in Uganda and Malawi: a prospective cohort studyMaternal triple antiretroviral exposure during both the ante-partum and post-partum phases did not result in greater developmental risks for the mothers' HIV-exposed and uninfected children through age 60 months, compared with children who were HIV-unexposed and uninfected. This might be because ante-partum triple antiretroviral protection of the health of mothers with HIV during pregnancy might be neuroprotective for the child, and when continued post partum, could enhance the quality of caregiving for the child through better clinical care for the mother. Full-Text PDF

IMPACT OF GUT MICROBIOTA ON VACCINE RESPONSE IN HIV EXPOSED INFANTS

Abstract Maternal HIV infection has been shown to alter the composition and diversity of gut microbiota in their infants. We hypothesized that inheritance of an altered microbiota in HIV-exposed uninfected (HEU) infants is associated with poor vaccine responses. Here, using a germ free mouse model, we investigate the causative relationship between stool microbiota in HEU infants and BCG vaccine response. BCG vaccine Th1 responses were assessed using a whole blood assay and an intracellular cytokine flow cytometry panel. Stool samples from time of BCG vaccination were collected, and those from high or low BCG responder infants transferred by oral gavage to germ free pups at day 5 after delivery. Five days after gavage, pups were sacrificed to analyze inherent immunity or vaccinated with 10^6 CFUs of BCG. Vaccinated animals were sacrificed 28 days post vaccination. BCG specific T cells were quantified using TB10.4 (class I) tetramers by flow cytometry. At d10 post-delivery, pups gavaged with high responder stool (Phr) had significantly lower spleen cell count compared to those gavaged with low responder stool (Plr). Furthermore, Phr pups had significantly higher proportions but not numbers of effector memory CD4 T cells (CD4+CD44hiCD62Llo) relative to Plr. Total number of B cells and neutrophils were significantly reduced in Phr vs Plr. When vaccinated with BCG, Phr displayed significantly higher number of TB10.4-specific CD8 T cells compared to Plr. Our data shows a direct role of the microbiota in inherent immunity in infants. Furthermore, the microbiota in low responder HEU infants caused reduced number of vaccine specific CD8 T cells. Together, we show for the first time that intestinal microbiota in human infants at birth impacts vaccine response.

Maternal Perinatal HIV Infection Is Associated With Increased Infectious Morbidity in HIV-exposed Uninfected Infants.

The aging population of females with perinatally-acquired HIV (PHIV) are having their own children. HIV-exposed uninfected infants (HEU-N) born to women living with non-perinatally-acquired HIV (NPHIV) experience higher infectious morbidity compared with HIV-unexposed infants (HUU). Little is known about the infectious morbidity risk of HIV-exposed uninfected infants (HEU-P) born to PHIV women. We evaluated prevalence of infectious cause hospitalizations (ICH) during the first year of life among HEU-P, HEU-N and HUU infants in a United States (U.S) tertiary care center. Maternal HIV status was categorized as PHIV vs. NPHIV vs. HIV-uninfected. Generalized Estimating Equation models were fit to evaluate the association between maternal HIV status and infant ICH. ICH was evaluated among 205 infants, 28 HEU-P infants, 112 HEU-N infants, and 65 HUU infants. PHIV women were younger compared with NPHIV and HIV-uninfected women (median age 22 years vs. 29 and 23 respectively, p<0.01). Overall, 21% of HEU-P, 4% of HEU-N and 12% of HUU infants experienced at least one ICH event (p<0.01) in the first year of life. After adjusting for confounders, HEU-P infants were at increased ICH risk compared with HEU-N infants [adjusted odds ratio (aOR)=7.45, 95% Confidence Interval (CI):1.58-35.04]. In sub-group analysis of HEU infants, excluding HUU infants, this relationship persisted after adjustment for maternal CD4 and HIV RNA level (aOR=10.24, 95% CI:1.66-63.31) CONCLUSIONS:: In a small U.S. cohort, HEU-P infants experienced increased ICH risk. Differences in intrauterine environments, social factors, or access to care may be important factors to assess in future larger studies.

Immune Activation and Microbial Translocation Markers in HIV-Exposed Uninfected Malawian Infants in the First Year of Life.

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. 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. 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). 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.

Lower Respiratory Tract Infections in Children in a Well-vaccinated South African Birth Cohort: Spectrum of Disease and Risk Factors.

Childhood lower respiratory tract infections (LRTIs) cause substantial morbidity and under-5 child mortality. The epidemiology of LRTI is changing in low- and middle-income countries with expanding access to conjugate vaccines, yet there are few data on the incidence and risk factors for LRTI in these settings. A prospective birth cohort enrolled mother-infant pairs in 2 communities near Cape Town, South Africa. Active surveillance for LRTI was performed for the first 2 years of life over 4 respiratory seasons. Comprehensive data collection of risk factors was done through 2 years of life. World Health Organization definitions were used to classify clinical LRTI and chest radiographs. From March 2012 to February 2017, 1143 children were enrolled and followed until 2 years of age. Thirty-two percent of children were exposed to antenatal maternal smoking; 15% were born at low birth weights. Seven hundred ninety-five LRTI events occurred in 429 children by February 2017; incidence of LRTI was 0.51 and 0.25 episodes per child-year in the first and second years of life, respectively. Human immunodeficiency virus (HIV)-exposed, uninfected infants (vs HIV-unexposed infants) were at increased risk of hospitalized LRTI in the first 6 months of life. In regression models, male sex, low birth weight, and maternal smoking were independent risk factors for both ambulatory and hospitalized LRTI; delayed or incomplete vaccination was associated with hospitalized LRTI. LRTI incidence was high in the first year of life, with substantial morbidity. Strategies to ameliorate harmful exposures are needed to reduce LRTI burden in vulnerable populations.

HIV-Exposed Uninfected Infants Have Increased Regulatory T Cells That Correlate With Decreased T Cell Function.

Background: HIV-exposed uninfected infants (HEU) are at higher risk of severe infections, hospitalizations and death compared with HIV-unexposed uninfected infants (HUU), but the immune deficit underlying it is not known. To address this gap, we investigated T cell functionality and its relationship to phenotypic profiles of T cells and antigen presenting cells (APC) in HEU and HUU.Methods: Blood mononuclear cells from 55 HEU and 16 HUU were stimulated with Staphylococcal Enterotoxin B (SEB) or mock for 72 h, and tested by flow cytometry for proliferation and expression of Th1, Th2, and regulatory (Treg) markers. In parallel, cells were phenotypically assessed for differentiation profiles of Treg, conventional T cell (Tconv) and APC in unstimulated cells.Results: HEU had lower CD4+ functional responses to SEB/mock and similar CD8+ responses compared with HUU. In the phenotypic T cell panel, HEU showed higher proportions of CD4+ and CD8+ Treg expressing IL10, FOXP3, and CD25; higher effector Tconv and Treg; and lower naïve and CD4+TGFβ+ Treg compared with HUU. In the phenotypic APC panel, HEU showed higher proportions of CD1c+ cDC2, CD123+ pDC, CD16+ inflammatory monocytes and cDC and higher expression of CD103 on CD1c-CD123-CD16-cDC1 compared with HUU. Regression analyses adjusted for HIV exposure and multiple comparisons showed that higher CD8+IL10+ and CD8+FOXP3+ Treg in unstimulated cells were associated with lower CD8+ T cell functional responses to SEB/mock. Functionality was not affected by Tconv differentiation, but higher APC activation in aggregate was associated with higher CD8+IL10+ Treg responses to SEB.Conclusions: T cell functionality was decreased in HEU compared with HUU. High CD8+ Treg proportions were the most important predictors of decreased T cell functionality in HEU and HUU.

Growth in syphilis-exposed and -unexposed uninfected children from birth to 18 months of age in China: a longitudinal study

Early infant growth and development has attracted worldwide attention. Although numerous studies have demonstrated that maternal syphilis increases the risk of adverse pregnancy outcomes and congenital syphilis, the subsequent growth pattern and morbidity of syphilis-exposed uninfected infants are less understood. We conducted a longitudinal study to compare the growth pattern and disease distribution of syphilis-exposed and syphilis-unexposed uninfected children, and World Health Organization (WHO) reference standards from birth to 18 months of age. We obtained data from a prospective cohort study in three representative regions of Zhejiang Province in China. A total of 333 syphilis-uninfected children born to women with syphilis were recruited at birth and matched with 333 syphilis-uninfected children born to women without syphilis during pregnancy. Children were followed-up by medical staff every 3 months until 18 months of age. The mixed-effects model was used to compare changes in growth patterns and influencing factors between the two groups. Mean weight, length, and head circumference of children, as well as disease prevalence, were similar between the groups. Multilevel analysis indicated that, after controlling confounders, growth velocities were comparable in both weight and length measures from birth to 18 months old between the two groups; however, low birth weight had a negative impact on weight gain in both groups. There was no significant negative association between syphilis exposure and early growth and health in children, under 18 months in a setting with universal coverage of therapeutic interventions for maternal syphilis. These findings may contribute to improving prevention efforts for mother-to-child transmission of syphilis, such as early screening for syphilis in pregnant women, universal coverage of treatment, and interventions for exposed children. Children with low birth weight should be given priority as this is a risk factor for weight gain.

Growth in HIV-1-exposed but uninfected infants treated with lopinavir–ritonavir versus lamivudine: a secondary analysis of the ANRS 12174 trial

The tolerance of antiretroviral drugs in infants must be carefully evaluated. In previous studies of children with HIV type 1 (HIV-1) less weight gain was observed in children given lopinavir-ritonavir-based combinations than those given nevirapine. We aimed to compare the effects of lopinavir-ritonavir and lamivudine on growth in HIV-exposed uninfected infants included in the ANRS 12174 trial. ANRS 12174 was a multicentre, randomised, controlled trial of infant prophylaxis to prevent HIV-1 transmission by breastfeeding done at four antenatal clinics in Burkina Faso, South Africa, Uganda, and Zambia. HIV-exposed uninfected infants born to asymptomatic mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL) were randomly assigned (1:1) to receive lopinavir-ritonavir or lamivudine 7 days after birth, with stratification by country. In a prespecified secondary analysis, we assessed the effect of lopinavir-ritonavir and lamivudine on the growth of these infants from day 7 until cessation of breastfeeding (maximum treatment time 12 months) in the modified intention-to-treat population, which included all children correctly enrolled with at least one follow-up anthropometric measurement. We compared the growth of infants, defined as children's WHO-defined length-for-age Z score (LAZ), weight-for-length Z score (WAZ), and weight-for-age Z score (WLZ). We used linear mixed effect and β spline-regression models to compare growth between the treatment groups. The trial is registered with ClinicalTrials.gov, number NCT00640263. 1273 HIV-exposed uninfected infants and their mothers were enrolled between Nov 16, 2009, and May 7, 2013, of whom 1266 (99%) infants were included in the modified intention-to-treat analysis (630 assigned to lopinavir-ritonavir, 636 assigned to lamivudine). Baseline characteristics of the infants and mothers were similar across the two treatment groups. No differences in least-squares (LS) mean LAZ were identified between the treatment groups at any timepoint. LS mean WLZ was significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·22 [95% CI -0·34 to -0·09], p=0·0006) and 50 weeks (-0·25 [-0·47 to -0·04], p=0·02). LS mean WAZ was also significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·18 [95% CI -0·30 to -0·05], p=0·01) and 50 weeks (-0·24 [-0·45 to -0·05], p=0·02). Linear mixed models showed that lopinavir-ritonavir was associated with decreases in WLZ and WAZ over time (p<0·0001 and p=0·002), whereas spline regression models indicated that these reductions occurred early and remained constant thereafter (p<0·0001 with a knot at 44 days for WLZ; p=0·02 with a knot at 118 days for WAZ). The difference in LS mean WLZ at 50 weeks between the treatment groups was higher among girls than boys (difference -0·29 [95% CI -0·58 to 0·01], p=0·05 for girls; -0·22 [-0·53 to 0·09], p=0·18 for boys). Less weight gain was observed in infants given lopinavir-ritonavir than those given lamivudine, which is indicative of a persistent effect that could have long-term deleterious effects. This finding merits attention considering the recommendations for early and lifelong treatment of infants with HIV. French National Agency for Research on AIDS and Viral Hepatitis, the Total Foundation, the European Developing Countries Clinical Trials Partnership, and the Research Council of Norway.

Prescription of Antibacterial Drugs for HIV-Exposed, Uninfected Infants, Malawi, 2004-2010.

Antimicrobial drug resistance is a serious health hazard driven by overuse. Administration of antimicrobial drugs to HIV-exposed, uninfected infants, a population that is growing and at high risk for infection, is poorly studied. We therefore analyzed factors associated with antibacterial drug administration to HIV-exposed, uninfected infants during their first year of life. Our study population was 2,152 HIV-exposed, uninfected infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition study in Lilongwe, Malawi, during 2004-2010. All infants were breastfed through 28 weeks of age. Antibacterial drugs were prescribed frequently (to 80% of infants), and most (67%) of the 5,329 prescriptions were for respiratory indications. Most commonly prescribed were penicillins (43%) and sulfonamides (23%). Factors associated with lower hazard for antibacterial drug prescription included receipt of cotrimoxazole preventive therapy, receipt of antiretroviral drugs, and increased age. Thus, cotrimoxazole preventive therapy may lead to fewer prescriptions for antibacterial drugs for these infants.

Growth of HIV-Exposed Infants in Southwest China: A Comparative Study.

Objectives. Prevention of mother-to-child HIV transmission has been globally successful leading to a decline in HIV-infected infants. Thus, the number of HIV-exposed, but uninfected, infants is increasing. As growth is an important indicator of child health, this study aimed to evaluate growth parameters of HIV-exposed Chinese infants. Methods. A prospective study was conducted among HIV-exposed (HIV-infected and uninfected) infants born during 2007 to 2015 in Liuzhou, China. Their weight and length were assessed longitudinally from birth to 18 months of age and compared with HIV-unexposed, uninfected (HUU) infants from the same region. Results. There were 467 HIV-exposed infants. Four percent of infants were HIV-infected. The mean weight-for-age (WAZ) and length-for-age (LAZ) z scores of HIV-infected infants were significantly lower than those of HIV-exposed but uninfected (HEU) infants during 9 to 18 months and 12 to 18 months of age, respectively. Additionally, the mean WAZ and LAZ scores of HIV-infected infants were significantly lower than HUU infants during the first 12 months and 18 months of life, respectively. The mean WAZ and LAZ scores of HEU infants were significantly lower than HUU infants during the first 12 months and 6 months of life, respectively. HEU infants also had a lower mean weight-for-length z score than HUU infants during the first 6 months. Conclusion. We demonstrated poor growth among HIV-exposed Chinese infants, including HIV-uninfected, compared with HUU infants. The results emphasize the need for nutritional monitoring and interventions for HIV-exposed infants regardless of HIV infection status. Research is needed on long-term growth trajectories and factors affecting growth of HIV-exposed infants in China.

Delayed Seroreversion in HIV-exposed Uninfected Infants.

Recent studies report delayed anti-HIV antibody clearance (seroreversion) among HIV-exposed uninfected infants that may affect diagnostic practices. We evaluated the age-specific seroreversion rates in Thailand. The medical records of HIV-exposed uninfected infants born in January 2000-December 2014 were reviewed. Anti-HIV seroreversion rates at 12, 18 and 24 months were analyzed in 3 periods according to the Thai National Guidelines of prevention of mother-to-child transmission of HIV: zidovudine with or without single dose nevirapine to all women (2000-2006), adding lamivudine plus nevirapine to zidovudine in women with CD4 count <200 cells/mm (2007-2009) and zidovudine plus lamivudine plus boosted lopinavir to all women (2010-2014). In 2013, the serologic test kit was changed from third- to fourth-generation (4G) assay. All the infants were formula fed. Among 736 infants, the overall seroreversion rates at 12, 18 and 24 months of age were 59.38%, 94.57% and 100%, respectively. The seroreversion rates at 12 months of age declined from 68% in 2000-2006 and 65.9% in 2007-2009, to 42.9% in 2010-2014 (P = 0.001). Seroreversion rates at 18 months of age were more than 96.5% before 2013 and decreased to 79.1% in 2013-2014 (P = 0.001) with use of 4G. Multivariate analysis identified antepartum protease inhibitors treatment and the use of 4G testing as independent factors associated with delayed seroreversion. Anti-HIV seroreversion delay in HIV-exposed uninfected infants was associated with use of protease inhibitors and 4G HIV testing, complicating the interpretation to exclude perinatal HIV infection.