A South African study has found that, in general, babies born to HIV-positive mothers who are on antiretroviral therapy do not have worse health outcomes than the children of HIV-negative mothers. However, according to an Aidsmap report, it did find that the HIV-positive mothers’ babies had more hospitalisations – especially for lower respiratory tract infections and diarrhoeal disease – in the period from eight days to three months after birth. Encouragingly, though, this health disadvantage disappeared in babies who received early and complete breastfeeding, and who also received the full course of recommended vaccines.
The report says in South Africa alone, 95% of pregnant women with HIV now receive ART (compared with 61% of all people with HIV) and as a result the number of children who acquire HIV per year has declined by 80%, from 70,000 to 13,000.
While these are considerable achievements, they have also had the effect of re-focusing attention on the children of HIV-positive mothers who do not acquire HIV. The report said previous studies had found that HIV-negative babies born to mothers with HIV generally had poorer health than the babies of negative mothers.
Dr Stanzi le Roux and her colleagues from the University of Cape Town therefore recruited pregnant women attending the Gugulethu Midwife Obstetric Unit in Cape Town into two cohorts, one for positive and one for negative women. This clinic sees a population with high infant mortality (2.3% of live births in 2013) and high HIV prevalence among mothers (30%).
After adjusting for factors including running water, flush toilets and postnatal depression (which of itself doubled the risk of hospitalisation during the eight days to three-month period), three factors were associated with the greater risk of hospitalisation for the babies of positive mothers.
The first was the mother’s state of health at the time of starting ART, and how soon they started it. The babies of mothers who started ART with CD4 counts over 350, viral loads below 10,000, and before 24 weeks of pregnancy, were not significantly more likely to be hospitalised than babies of negative mothers.
Of even more influence was whether the babies received all their vaccinations, and whether they were optimally breastfed for those three months. Both of these needed to happen to reduce the relative risk of hospitalisation, compared with the risk to the HIV-negative mothers’ babies, to zero.
Having complete vaccines but suboptimal breastfeeding did not significantly reduce the risk. Optimal breastfeeding but incomplete vaccines reduced the risk a little, so that it became statistically non-significant, but there were only 14 mother-baby pairs in this category.
The report says the findings of this study are hopeful, in that the researchers found that the babies born to mothers with HIV who are given timely antiretroviral therapy, and who do not acquire HIV themselves, are at most time points as healthy as the children of HIV-negative mothers. There was no difference in mortality. Although there was a difference in hospitalisation rates between a week and three months after birth, this difference was eradicated by vaccinating against the most lethal infant infections, and by exclusive breastfeeding during those three months.
Abstract
Background: Without breastfeeding and maternal antiretroviral therapy (ART), HIV-exposed uninfected (HEU) infants have greater infectious morbidity than HIV-unexposed (HU) infants. We hypothesised that with the introduction of universal maternal ART, breastfed HEU and HU infants would have similar morbidity.
Methods: We prospectively studied a cohort of HIV-infected pregnant women initiating ART, and a parallel group of HIV-uninfected pregnant women, starting from their first antenatal care visit at the Gugulethu Midwife Obstetrics Unit in Cape Town, South Africa. All pregnant women attending their first antenatal care visit were eligible for enrolment if aged 18 years or older and planning to deliver in Cape Town, without gestational age restrictions. HIV-infected women were participants of the Maternal Child Health ART (MCH-ART) study, and HIV-uninfected women were participants of the HIV-Unexposed Uninfected (HU2) study. All enrolled women were followed up during pregnancy and through delivery. At the early neonatal visit (scheduled for the first week after birth), mother–infant pairs who practiced any breastfeeding in the first 7 days of life were eligible for further postnatal follow-up for at least 12 months post partum. HIV infection was excluded among HEU infants at ages 6 weeks and 12 months by PCR. We evaluated the effect of HIV exposure on two primary outcomes: hospitalisation (all-cause and infection-related admission to hospital) and longitudinal prevalence of child infectious illness (diarrhoea and presumed lower respiratory tract infection [LRTI]). Hospitalisation data were abstracted from routine health records. Crude and adjusted incidence rate ratios (aIRRs; with adjustment for maternal HIV disease severity, timing of ART initiation, breastfeeding, timely vaccination, and birth outcomes [gestational size and age]) for infection-related hospitalisations were calculated from Poisson regression models (with variance corrected for clustering). Prevalence of infant infectious illness was based on maternal self-report for the preceding 2 weeks of each visit, with questions based on Demographic and Health Survey (DHS) questionnaires. Infants who acquired HIV infection during follow-up were excluded from this analysis. MCH-ART is registered on ClinicalTrials.gov, NCT01933477.
Findings: Pregnant women were recruited between March 20, 2013, and Aug 19, 2015. Mother–infant pairs (HEU, n=459; HU, n=410) were followed up for a median of 12 months until March 24, 2017. Compared with HU infants, HEU infants had more infection-related hospitalisations between the age of 8 days and 3 months (HEU, 34·2 admissions per 100 child-years [24·4–47·9] vs 9·8 per 100 child-years [95% CI 5·1–18·8]; IRR 3·50 [95% CI 1·68–7·30]), but rates were similar at other ages. In infants aged 8 days to 3 months, infection-related hospitalisations for HEU infants with healthier mothers (n=84; ART initiation at <24 weeks' gestation, CD4 count >350 cells per μL, HIV viral load <4·0 log 10 copies per mL: 15·88 admissions per 100 child-years [5·12–49·23]) approximated those of HU infants (9·77 per 100 child-years [5·08–18·78]; aIRR 1·28 [0·27–6·05]). HEU infants of mothers with late ART initiation (at ≥24 weeks' gestation) and advanced disease (CD4 count ≤350 cells per μL and HIV viral load ≥4·0 log 10 copies per mL; n=44) had the highest admission rate (40·44 per 100 child-years [15·18–107·74]; aIRR 5·01 [1·50–16·71]). In this age group, reduced admissions were seen in HEU infants with optimal breastfeeding (initiated within 1 h of birth and exclusive through age 3 months) and timely vaccination (required doses received within 2 weeks of indicated age; n=90; 9·63 admissions per 100 child-years [2·41–38·49]). Between birth and age 6 months, HEU infants had an almost five times greater prevalence of LRTIs than HU infants (aPR 4·69 [2·40–9·17]), and a three-times greater prevalence of diarrhoeal illness (aPR 2·93 [1·70–5·07]). After age 6 months, these associations were ameliorated.
Interpretation: Despite ART in pregnancy, breastfed HEU infants versus breastfed HU infants had transiently increased infectious morbidity risks in early infancy. However, differences were driven by factors potentially amenable to intervention, including delayed diagnosis and ART initiation in HIV-positive mothers, and suboptimal breastfeeding and vaccination of their infants.
Funding: US National Institute of Child Health and Human Development, Elizabeth Glaser Pediatric AIDS Foundation, South African Medical Research Council, Fogarty Foundation and the Office of AIDS Research.
Authors
Stanzi M le Roux, Elaine J Abrams, Kirsten A Donald, Kirsty Brittain, Tamsin K Phillips, Allison Zerbe, David M le Roux, Max Kroon, Landon Myer
[link url="http://www.aidsmap.com/news/feb-2020/babies-south-african-mothers-taking-hiv-therapy-have-worse-health-early-months-unless"]Full Aidsmap report[/link]
[link url="https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(19)30375-X/fulltext"]The Lancet Child and Adolescent Health abstract[/link]