Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia

Abstract

Background Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. Methods We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6–10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. Results Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6–10 weeks were lower among infants who were HEU vs HU [β = − 0.29 (95% CI: − 0.46, − 0.12) and [β = − 0.42 (95% CI: − 0.68, − 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = − 0.28 CI: − 0.50, − 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6–10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = − 0.30 CI: − 0.59, − 0.01)] at 6 months, without other anthropometric differences at either site. Conclusion Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.

No Difference in Growth Outcomes up to 24 Months of Age by Duration of Exposure to Maternal Antiretroviral Therapy Among Children Who Are HIV-Exposed and Uninfected in Malawi

“…In our study, 88% of CHEU were exposed to ART from conception or first or second trimester and 98% via breast milk, comparable with population-level estimates ( 38 ). Reassuringly, our data present strong evidence of no difference in WAZ or LAZ by timing of ART exposure, similar to other findings in Eastern and Southern Africa ( 20 , 21 , 23 ). In a prospective cohort of South African and Zambian CHEU (2017–2018), exposure from conception or later during gestation was not associated with any differences in WAZ, LAZ, or WLZ at 6–10 weeks or 6 months, whereas a Malawian prospective cohort (2014–2016) observed no difference in mean weight or height in CHEU exposed to ART up to the age of 18 months ( via breast milk) compared with CHU ( 20 ).…”

“…Our data highlight that CHEU repeatedly presented with lower WAZ and LAZ than the reference population, with some evidence of early catch-up growth from enrollment to visit 1, although not prolonged as z-scores declined by visit 2. Our findings approximate those of previous Eastern and Southern African studies ( 10 – 15 , 17 , 21 ), including a large cohort of South African CHEU, where ART coverage in pregnancy was estimated at 96–97% (2013–2016) ( 37 ) and CHEU presented with negative LAZ between the ages of 6 weeks and 12 months, with some recovery between 6 weeks and 3 months of age ( 10 ). Consistent with our findings, several studies [conducted when antenatal ART coverage was estimated at 85–90% in Eastern and Southern Africa ( 37 )] have reported a decline in WAZ or LAZ in CHEU starting as early as the age of 3 months and often between the ages of 6 and 9 months, around the time of introduction to complementary foods ( 10 , 11 , 17 , 20 ).…”

A Systematic Review on Cardiometabolic Risks and Perinatal Outcomes among Pregnant Women Living with HIV in the Era of Antiretroviral Therapy

“…Therefore, 201 full texts were retrieved and subjected to screening, from which nine were excluded as they were research protocols, one was retracted from a journal, 45 did not include pregnant HIV women, seven were not on HIV, 34 were not on ART, and 74 did not report any outcome of interest, such as any outcome of perinatal or marker of CMR. Only 31 clinical studies [ 12 , 26 , 33 , 36 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ] conducted on 20,904 HIV women on ART before or during pregnancy were found relevant based on our eligibility criteria ( Figure 1 ). These clinical studies were published in peer-reviewed journals between 1999 and 2023.…”

“…These clinical studies were published in peer-reviewed journals between 1999 and 2023. The publications were from Southern Africa (South Africa [ 45 , 52 , 69 ] and Botswana [ 66 ], Eastern Africa (Ethiopia [ 36 ], Tanzania [ 69 ], Kenya [ 64 ], Uganda [ 60 , 62 , 69 ], Mozambique [ 33 , 61 ], Malawi [ 69 ], Zambia [ 52 , 69 ], and Zimbabwe [ 69 ]), Southern Europe (Spain [ 46 , 47 ]), Northern Europe (United Kingdom [ 55 ]) and Western Europe (Netherlands [ 12 , 57 ]), Eastern Asia (China [ 26 , 67 ]), Southern Asia (India [ 69 ] and Thailand [ 49 ]), Southern America (Brazil [ 43 , 50 , 51 , 56 ]) and Northern America (Canada [ 60 ] and USA [ 44 , 48 , 53 , 54 , 58 , 59 , 60 , 63 , 65 , 68 ]). The characteristics of included studies are presented in Table 1 .…”

The safety and immunogenicity of vaccines administered to pregnant women living with HIV: a systematic review and meta-analysis

“…The majority of these live in low-and-middle income countries (LMICs) particularly SSA, where the HIV burden is highest. 4 , 5 Higher infection related morbidity, impaired growth patterns, and higher mortality rates are reported in HEU infants compared with HIV-unexposed uninfected infants (HUU). 4 , 6 , 7 , 8 In infancy, the burden of infections is higher for HEU than HUU particularly in the first six months of life; this is partly attributed to the low levels of placentally transferred antibodies from PWLWH compared to pregnant women without HIV (PWWH).…”