Infants Of HIV-infected Mothers Research Articles

Growth and Neurodevelopment Outcomes in HIV-, Tenofovir-, and Efavirenz-Exposed Breastfed Infants in the PMTCT Option B+ Program in Malawi.

Pregnant and breastfeeding women in Option B+ in Malawi received antiretroviral drugs (ARVs) containing efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). However, effects on growth, renal, bone metabolism, and neurodevelopment of long-term exposure to low doses of these drugs through breast milk in HIV-exposed infants are unclear. Prospective cohorts of TDF-and-EFV-exposed and TDF-and-EFV-unexposed breastfed infants of HIV-infected and HIV-uninfected mothers in Option B+ were recruited in 2:1 ratio, respectively, followed from birth to 18 months. Infants with low birth weight, premature birth, and congenital abnormalities were excluded. Anthropometrics were assessed at birth, 6 weeks, 3, 6, 12, and 18 months. Neurodevelopment assessments used the Bayley Scales of Infant and Toddler Development III from 6 weeks. Creatinine, alkaline phosphatase, and phosphorus were assessed at 3, 6, and 12 months. Of 260 HIV-and-ARV-exposed and 125 HIV-and-ARV-unexposed infants enrolled at birth, 87% and 57%, 78% and 59%, 77% and 54%, 73% and 51%, and 65% and 43% completed 6-weeks, 3, 6, 12, and 18 months visits, respectively. There were no significant differences in the mean Z-scores for length-for-age, weight-for-age, weight-for-length, mid-upper arm circumference-for-age, and head circumference-for-age between groups except at 6-weeks for length-for-age. No bone fractures occurred. Neurodevelopment outcomes were similar between groups. Of creatinine, alkaline phosphatase, and serum phosphate measurements, 1.7%, 2.6%, and 3.3% reached any toxicity levels grades 1-4, respectively, with no differences between groups. Long-term exposure to EFV and TDF through breastfeeding in infants of HIV-infected mothers does not seem to result in significant growth, neurodevelopment, renal, or bone adverse outcomes. Data support safety of breastfeeding through 18 months within the Option B+ program.

Subclinical tuberculosis and adverse infant outcomes in pregnant women with HIV.

BACKGROUND: Tuberculosis (TB) in pregnant women with HIV is associated with adverse maternal and infant outcomes. Previous studies have described a substantial prevalence of subclinical TB in this group, but little is known about the impact of subclinical TB on maternal and pediatric outcomes.METHODS: The Tshepiso Study recruited 235 HIV-infected pregnant women with TB (and matched HIV-positive, TB-negative pregnant controls), in Soweto, South Africa, from 2011 to 2014. During enrolment screening, some women initially recruited as controls were subsequently diagnosed with prevalent TB. We therefore assessed the prevalence of subclinical TB, associated participant characteristics and outcomes.RESULTS: Of 162 women initially recruited as TB-negative controls, seven (4.3%) were found to have TB on sputum culture. All seven had negative WHO symptom screens, and six (86%) were smear-negative. Of their seven infants, one was diagnosed with TB, and three (43%) experienced complications compared to zero infants with TB and 11% experiencing complications in the control group of TB-negative mothers (P = 0.045).CONCLUSION: We discovered an appreciable prevalence of subclinical TB in HIV-infected pregnant women in Soweto, which had not been detected by screening algorithms based solely on symptoms. Infants of HIV-infected mothers with subclinical TB appear to have a higher risk of adverse outcomes than those of TB-negative mothers.

A study of the prevalence of hepatitis B virus infection in the infants of HIV-infected mothers in South Africa

Background: Worldwide approximately 240 million people have chronic hepatitis B virus (HBV) infection. The majority of chronic infections are acquired either from mother-to-child transmission (MTCT) or in early childhood. In South Africa, HBV immunization is given at six weeks of age. This is too late to prevent vertical transmission of HBV. This study aimed to determine the prevalence of HBV infection in babies born to HIV-infected mothers. Methods & Materials: A total of 916 samples were collected from infants born to HIV-infected mothers in Johannesburg, Durban and Cape Town, South Africa. Data collection took place at study entry and together with blood sampling at 25 and 60 weeks of age. The data includes HIV status, mode of delivery, birth weight, CD4 count, nutritional status, HBV immunization status. HBV markers (HBsAg, anti-HBs and anti-HBc) and anti-HCV antibodies were tested on the Architect (Abbott). All HBsAg positive samples were neutralized for confirmation. Confirmed HBsAg-positive samples were tested for HBV DNA and quantified against a WHO standard to determine HBV loads. HBV strain characterisation by sequencing of the HBsAg gene and genotyping by phylogenetic analysis using HepSEQ (www.hepseq.org.uk) is being done. Results: Of the 916 samples at 60 weeks of age, 852 were available for testing. Our preliminary data shows that of these, three samples are HBsAg positive with high HBV viral loads. An additional two samples show evidence of past HBV infection. Further testing on 25 week samples from these infants will be performed to determine timing of infection and sequencing will be performed at both time points. The mothers of these infants will be traced and tested. Conclusion: This study provides evidence of HBV infection in the infants of HIV-infected mothers in the era of HBV vaccination.

Postnatal weight gain in infants of HIV infected mothers: is formula feeding truly advantageous?

<h3>Aims</h3> British HIV Association guidelines recommend formula feeding for infants born in the UK to HIV infected mothers. Formula feeding is however associated with childhood obesity and adverse implications for longer term health. Local clinical observation suggested that infants of Black African HIV infected mothers demonstrate accelerated postnatal growth compared to their Caucasian counterparts, perhaps due to lack of familiarity with formula feeding in the former population. The aim of this study was to review postnatal growth in an unselected population of HIV exposed infants, and to compare different ethnic groups. <h3>Methods</h3> Retrospective case note review of all HIV exposed infants born at term over a three year period in a single centre (n= 44). 36 infants were born to Black African mothers, and 8 infants to Caucasian mothers. The majority of mothers (91%) had an undetectable viral load at delivery. Infants were weighed and measured at outpatient follow up at six weeks, three months, nine months and 18 months of age. Weight-for-age, length-for-age and BMI-for-age Z scores were calculated using LMS Growth software. <h3>Results</h3> Birth weights did not differ between groups. As a whole infants born to HIV infected mothers grew similarly to WHO standards until nine months of age, but Black African infants were heavier than Caucasian infants by age three months (mean (SD) BMI z-score 0.55 (1.06) v −0.34 (0.93); p&lt;0.05). Both groups showed accelerated weight gain to 18 months: mean (SD) BMI z-score 1.58 (0.78) in Black African v 0.94 (1.04) in Caucasian infants. <h3>Conclusion</h3> Infants born in Scotland to Black African HIV infected mothers are on average above the 91st WHO centile for BMI by 18 months of age. Further research is required to establish if this reflects inappropriate formula feeding practice. Babies of HIV infected mothers with undetectable viral load at delivery are at very low risk of perinatal transmission: feeding recommendations should consider the potential longer term adverse consequences of formula feeding in this population.

HIV Infection and the Incidence of Malaria Among HIV-Exposed Children from Tanzania

To determine whether human immunodeficiency virus (HIV) infection is associated with increased risk of malaria incidence and recurrence in children. Newborn infants of HIV-infected mothers were enrolled at 6 weeks and followed for 2 years. HIV status was assessed by enzyme-linked immunosorbant assay and confirmed by HIV DNA polymerase chain reaction. Malaria was defined as (1) physician-diagnosed clinical malaria; (2) probable malaria, in which laboratory testing is requested for parasitemia; and (3) blood smear-confirmed malaria. Cox proportional hazards models estimated hazard ratios (HRs) for development of first and second malaria episodes, and generalized estimating equation models estimated malaria rate differences per 100-child-years in relation to time-updated HIV status. Child HIV infection was associated with clinical (HR, 1.34; 95% confidence interval [CI], 1.12-1.61), probable (HR, 1.47; 95% CI, 1.19-1.81), and confirmed (HR, 1.67; 95% CI, 1.18-2.36) malaria episodes. Per 100 child-years, HIV-infected children experienced 88 (95% CI, 65-113), 36 (95% CI, 19-53), and 20 (95% CI, 9-31) more episodes of clinical, probable, and confirmed malaria episodes, respectively, than HIV-uninfected children. Among children with ≥1 malaria episodes, those with HIV infection developed second clinical (HR, 1.28; 95% CI, 1.04-1.57), probable (HR, 1.60; 95% CI, 1.26-2.14), and confirmed (HR, 2.27; 95% CI, 1.06-3.89) malaria sooner than HIV-uninfected children. HIV infection is a risk factor for the development of malaria. Proactive malaria disease prevention and treatment is warranted for all children, particularly those with HIV infection in settings of coendemicity.

Association of Prenatal and Postnatal Exposure to Lopinavir-Ritonavir and Adrenal Dysfunction Among Uninfected Infants of HIV-Infected Mothers

Association of Prenatal and Postnatal Exposure to Lopinavir-Ritonavir and Adrenal Dysfunction Among Uninfected Infants of HIV-Infected Mothers

Micronutrient Fortification to Improve Growth and Health of Maternally HIV-Unexposed and Exposed Zambian Infants: A Randomised Controlled Trial

BackgroundThe period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age.Methods and FindingsWe conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z<−2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors.ConclusionsIn the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants.Trial registrationControlled-Trials.com ISRCTN37460449

Effect of a Point‐of‐Use Water Treatment and Safe Water Storage Intervention on Diarrhea in Infants of HIV‐Infected Mothers

To reduce mother-to-child transmission of human immunodeficiency virus (HIV) in resource-poor settings, the World Health Organization recommends exclusive breast-feeding for 6 months, followed by rapid weaning if replacement feeding is affordable, feasible, available, safe, and sustainable. In the Kisumu Breastfeeding Study (trial registration: Clinicaltrials.gov identifier NCT00146380), infants of HIV-infected mothers who received antiretroviral therapy experienced high rates of diarrhea at weaning. To address this problem, mothers in the Kisumu Breastfeeding Study were given safe water storage vessels, hygiene education, and bleach for household water treatment. We compared the incidence of diarrhea in infants enrolled before (cohort A) and after (cohort B) implementation of the intervention. Cohort B infants experienced less diarrhea than cohort A infants, before and after weaning (P < .001 and P = .047, respectively); however, during the weaning period, there were no differences in the frequency of diarrhea between cohorts (P = 0.89). Testing of stored water in cohort B homes indicated high adherence (monthly range, 80%-95%) to recommended chlorination practices. Among infants who were weaned early, provision of safe water may be insufficient to prevent weaning-associated diarrhea.

Formula Feeding vs. Breast-Feeding for Infants of HIV-Infected Mothers

Formula feeding can reduce infant postpartum exposure to HIV from an infected mother. When mothers lack access to clean water, however, breast-feeding can be more effective for limiting overall morbidity. Furthermore, cost and stigma limit use of formula in some places. Further insights about feeding strategies for HIV-exposed infants come from the Mashi study, a randomized trial with a 2x2 factorial design conducted in southern Botswana. Part one of the trial documented no infant benefit from adding nevirapine to a mother’s AZT peripartum regimen, but did …

The effect of Pretoria Pasteurization on bacterial contamination of hand-expressed human breastmilk.

One of the challenges facing the development of programs to reduce mother to child transmission of HIV in developing countries remains the problem of infant feeding. One of the alternative feeding methods under investigation for infants of HIV-infected mothers is heat treatment of expressed breastmilk by Pretoria Pasteurization. The objective of this study was to determine the effect of Pretoria Pasteurization on commensal and pathogenic bacteria in hand-expressed human breastmilk, and to determine the duration of time for which milk can be kept safely without refrigeration after Pretoria Pasteurization. Samples of milk were hand expressed by lactating women in the postnatal ward. The samples were split into control and pasteurized specimens. The pasteurized specimens underwent Pretoria Pasteurization. All samples were stored at room temperature and were sampled for bacterial culture every 4 h, up to 12 h. Clinically significant levels of bacterial contamination occurred in 59 per cent of control and 7.8 per cent of pasteurized samples. Four pasteurized samples showed significant contamination. There is strong evidence that the contaminating organisms in these samples were introduced by handling after pasteurization. The 53 (91 per cent) pasteurized samples that had no contamination at 4 h remained sterile for the remainder of the standing period of 12 h. Forty-one per cent of control samples already had significant growth after standing at room temperature for 4 h. In conclusion, Pretoria Pasteurization kills pathogenic and commensal bacteria in hand-expressed breastmilk. Expressed breastmilk that has undergone Pretoria Pasteurization can be kept without refrigeration for up to 12 h with minimal probability of bacterial contamination provided that it is kept in the pasteurization container and is not handled.

Evaluation of a pilot programme and a follow-up study of infant feeding practices during the scaled-up programme in Botswana

This paper describes the results of two studies concerning a programme to prevent mother-to-child transmission of HIV in Botswana. The programme included VCT, provision of oral AZT to the HIV infected mothers and to the infant, infant feeding counselling and support, and free provision of formula for infants of HIV infected mothers who opted not to breastfeed. The study evaluating the pilot phase of the programme concluded that the programme should be scaled up. After the programme expanded, a follow-up evaluation of infant feeding practices was conducted. Infant feeding practices differed significantly between intervention and non-intervention sites and between mothers of unknown HIV status, non-infected mothers and HIV-infected mothers. Among the infected mothers who chose exclusive formula feeding, 96% maintained this up to the time of interview. Health workers' knowledge about HIV transmission was weak. Counselling on feeding needs to be improved in many areas.

Exclusively Breastfed Infants are Less Likely Than Those Given Supplements to Contract HIV from Their Mother

This article discusses the results of the South African and Malawian study on the likelihood of vertical transmission of HIV during breast-feeding. The South African study was conducted between July 1995 and April 1998 using data from 549 HIV-infected mothers and infants who were tested for HIV seropositivity at 1 and 6 weeks and at 3 months. Cumulative probability of a positive HIV test was assessed among three subgroups: 156 babies who never breast-fed 103 babies who breast-fed exclusively and 288 babies who received breast milk supplementation. Findings revealed that an estimated 19% of never-breast-fed and 21% of ever-breast-fed infants were HIV-positive at 3 months of age. Also the large difference in postnatal transmission between babies exclusively breast-fed and those who received mixed feedings may be due to feeding practices. On the other hand the Malawian study conducted during 1994-97 examined the HIV status of 672 infants of HIV-infected mothers through follow-up visits at 6 weeks and 3 months postpartum. In addition tests for HIV infection were performed at 6-month intervals. After the 24-month follow-up no seroconversion after being weaned and a significant decline in HIV infection rates within the first 2 years were noted. Furthermore the cumulative risk of HIV-1 infection among breast-fed babies steadily increased over the first 24 months. The researchers generally concluded that balancing the risk of HIV transmission with the benefits of breast milk requires the consideration of individual mothers.

Neurodevelopmental outcomes of Ugandan infants with HIV infection: an application of growth curve analysis.

Neurodevelopmental outcomes of human immunodeficiency virus Type 1 (HIV-1)-infected infants of non-drug-using mothers were assessed in a controlled, prospective study from birth to 24 months with 3 groups: 61 infants of HIV-infected mothers, 234 uninfected infants of HIV-infected mothers (seroreverters), and 115 uninfected infants of uninfected mothers. Compared with seroreverters and uninfected infants, HIV-infected infants demonstrated lower mental and motor development on the Bayley Scales and greater deceleration in their rate of motor development. HIV-infected infants with abnormal neurologic exams had lower motor and mental test scores and lower rates of motor Bayley Scales scores than their HIV-infected counterparts with normal neurologic exams. Contrary to prediction, no group differences in mean performance or growth rates were found on visual information processing on the Fagan Test of Infant Intelligence.

The pediatric pulmonary and cardiovascular complications of vertically transmitted human immunodeficiency virus (P 2C 2 HIV) infection study: Design and methods

The P 2C 2 HIV Study is a prospective natural history study initiated by the National Heart, Lung, and Blood Institute in order to describe the types and incidence of cardiovascular and pulmonary disorders that occur in children with vertically transmitted HIV infection (i.e., transmitted from mother to child in utero or perinatally). This article describes the study design and methods. Patients were recruited from five clinical centers in the United States. The cohort is composed of 205 infants and children enrolled after 28 days of age (Group I) and 612 fetuses and infants of HIV-infected mothers, enrolled prenatally (73%) or postnatally at age <28 days (Group II). The maternal-to-infant transmission rate in Group II was 17%. The HIV-negative infants in Group II (Group llb) serves as a control group for the HIV-infected children (Group IIa). The cohort is followed at specified intervals for clinical examination, cardiac, pulmonary, immunologic, and infectious studies and for intercurrent illnesses. In Group lla, the cumulative lossto-follow-up rate at 3 years was 10.5%, and the 3-year cumulative mortality rate was 24.9%. The findings will be relevant to clinical and epidemiologic aspects of HIV infection in children.

Use of polymerase chain reaction and quantitative antibody tests in children born to human immunodeficiency virus‐1‐infected mothers

The diagnosis of human immunodeficiency virus (HIV) infection in children born to HIV-infected mothers is complicated by the presence of passively acquired maternal antibodies, and exclusion of infection in these infants remains problematic. The use of genome detection by polymerase chain reaction (PCR) amplification and the quantification of anti-HIV-1 antibodies were examined as methods for early diagnosis. Blood samples were taken from 84 non-breast-fed infants of HIV-infected mothers in five Italian and Spanish centres, a subgroup of children enrolled in the European Collaborative Study (ECS) for whom clinical and immunological information has been documented from birth. Whole blood was added to glycigel cryopreservative, stored, and tested in the United Kingdom by a nested PCR method. Antibody to HIV-1 was detected and quantified by titration using a gelatin particle agglutination test. PCR sensitivity and specificity were assessed. Twenty-one of the 84 children tested were infected. The estimated PCR sensitivity ranged from 0% (95% CI 0-26%) on day 1, 57% (19-85) on day 7, to 63% (33-92) on day 30. The negative predictive value of PCR ranged from 85% (83-88) on day 0 to 98% (94-100) at 3 months of age. On average, the level of maternal antibody halved every 33 days (31-36.5) in uninfected children. Between 6 and 9 months of age, increases in antibody titres in infected children were not more informative than absolute levels. These findings suggest that antibody measurement may supplement genomic diagnosis and that this collection method provides an alternative to the use of dried blood spots.

Construction of gag, pol, and env specific riboprobes for confirmation of HIV-1 specific polymerase chain reaction products.

Conserved regions of the gag, pol, and env genes of HIV-1 pBH10 DNA (gag nucleotides(nt)1508-1652, pol nt 2811-3118, env nt 7792-7934; Ratner et al., 1985) were amplified by the polymerase chain reaction (PCR) using oligonucleotides complementary to the termini of these regions as primers. Primer areas of the amplified DNA were then removed by digestion with restriction endonucleases, and the internal fragments purified and cloned in both orientations into the 'riboprobe' transcription vector pGEM-5Z. Riboprobes made from these plasmids did detect the specific sequences of pBH10 DNA and of HIV-1 DNA amplified by PCR from clinical material. The riboprobes will be useful to confirm the specificity of PCR-amplified fragments of lymphocyte DNA obtained from infants of HIV-infected mothers and from high risk, but seronegative contacts of HIV-1 infected individuals.

Construction of gag, pol, and env specific riboprobes for confirmation of HIV-1 specific polymerase chain reaction products

Conserved regions of the gag, pol, and env genes of HIV-1 pBHIO DNA ( gag nucleotides(nt) 1520–1665, pol nt 2326–2663, env nt 7192–7333; Ratner et al., 1985) were amplified by the polymerase chain reaction (PCR) using oligonucleotides complementary to the termini of these regions as primers. Primer areas of the amplified DNA were then removed by digestion with restriction endonucleases, and the internal fragments purified and cloned in both orientations into the ‘riboprobe’ transcription vector pGEM-5Z. Riboprobes made from these plasmids did detect the specific sequences of pBH10 DNA and of HIV-1 DNA amplified by PCR from clinical material. The riboprobes will be useful to confirm the specificity of PCR-amplified fragments of lymphocyte DNA obtained from infants of HIV-infected mothers and from high risk, but seronegative contacts of HIV-1-infected individuals.

Epidemiology of vertically transmitted HIV-1 infection in Switzerland: results of a nationwide prospective study. Swiss Neonatal HIV Study Group.

A nationwide study involving 286 children of human immunodeficiency virus (HIV)-infected mothers living in Switzerland has been performed with the participation of all paediatricians interested in HIV infection in the country. Of these children 201 could be followed up prospectively from birth up to a median age of 22 months. Prevalence of HIV infection in Swiss parturients was estimated at 0.1% and apparently remained stable from 1986 to 1989. Vertical transmission rate was estimated at 14%-20%. Variables of maternal or perinatal history were not associated with transmission rate. Transmission to pairs of siblings of the same mothers was discordant in 33% (6 of 18), with always the elder sibling being infected. Postneonatal mortality in infants of HIV-infected mothers followed up from birth was increased 15-fold over the general population with a very high incidence (2 in 100) of sudden infant death apparently unrelated to HIV infection.

Mother‐to‐child transmission of human immunodeficiency virus

Transmission of HIV virus from an infected mother to her offspring is becoming the leading cause of spreading in the pediatric population. This is particularly burdensome in the pattern II countries where HIV infection has reached epidemic proportions and infection rates affect more women of childbearing age than men. During the last few years considerable effort has been directed at defining the optimal methods for identifying infants of HIV-infected mothers who will themselves prove to be infected because conventional serological assessment is impaired due to placental transfer of maternal IgG. At present, detection of specific IgA to HIV proteins, evaluation of autochthonous antibody production in vitro from infants' lymphocytes, and gene amplification of HIV DNA/RNA by polymerase chain reaction are the most promising procedures for early diagnosis within the first 6 months of life. Nevertheless all these techniques are cumbersome when evaluating specimens from the newborn child. Many studies have been performed to identify those maternal factors affecting the risk of vertical transmission. So far, none of them has shown real prognostic value. However, evaluation of maternal antibody response to functional epitopes of HIV envelope proteins such as the principal neutralizing domain, in some epidemiological settings, seems to correlate to a reduced rate of mother-to-child transmission.