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Randomized Controlled Trial
. 2022 Nov 28;226(11):2002-2009.
doi: 10.1093/infdis/jiac416.

Lower Insulin Sensitivity in Newborns With In Utero HIV and Antiretroviral Exposure Who Are Uninfected in Botswana

Jennifer Jao  1   2   3 , Shan Sun  2 , Lauren B Bonner  4 , Justine Legbedze  2 , Keolebogile N Mmasa  4 , Joseph Makhema  4 , Mompati Mmalane  4 , Samuel Kgole  4 , Gosego Masasa  4 , Sikhulile Moyo  4 , Mariana Gerschenson  5 , Terence Mohammed  4 , Elaine J Abrams  6 , Irwin J Kurland  7 , Mitchell E Geffner  8 , Kathleen M Powis  3   9   10   11
Affiliations
Randomized Controlled Trial

Lower Insulin Sensitivity in Newborns With In Utero HIV and Antiretroviral Exposure Who Are Uninfected in Botswana

Jennifer Jao et al. J Infect Dis. .

Abstract

Background: Few data exist on early-life metabolic perturbations in newborns with perinatal HIV and antiretroviral (ARV) exposure but uninfected (HEU) compared to those perinatally HIV unexposed and uninfected (HUU).

Methods: We enrolled pregnant persons with HIV (PWH) receiving tenofovir (TDF)/emtricitabine or lamivudine (XTC) plus dolutegravir (DTG) or efavirenz (EFV), and pregnant individuals without HIV, as well as their liveborn infants. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Preprandial homeostasis model assessment for insulin resistance (HOMA-IR) was assessed at birth and 1 month. Linear mixed models were fit to assess the association between in utero HIV/ARV exposure and average HOMA-IR from birth to 1 month, adjusting for confounders.

Results: Of 450 newborns, 306 were HEU. HOMA-IR was higher in newborns HEU versus HUU after adjusting for confounders (mean difference of 0.068 in log HOMA-IR, P = .037). Among newborns HEU, HOMA-IR was not significantly different between TDF/XTC/DTG versus TDF/XTC/EFV in utero ARV exposure and between AZT versus NVP newborn postnatal prophylaxis arms.

Conclusions: Newborns HEU versus HUU had lower insulin sensitivity at birth and at 1 month of life, raising potential concern for obesity and other metabolic perturbations later in life for newborns HEU.

Clinical trials registration: NCT03088410.

Keywords: in utero HIV exposure; insulin sensitivity; metabolic; perinatal HIV exposure.

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Conflict of interest statement

Potential conflicts of interest . MEG has a research contract from Novo Nordisk; serves as a consultant/advisory board member/advisor for Adrenas, Daiichi-Sankyo, Eton Pharmaceuticals, Ferring, Gilead, Neurocrine Biosciences, Novo Nordisk, Nutritional Growth Solutions, Pfizer, and QED; acts as a data safety monitoring board member for Ascendis, Millendo, and Tolmar; receives royalties from UpToDate and McGraw-Hill; and receives consultant fees from Gilead Sciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Consort diagram showing the study population enrolled and analyzed. Abbreviations: 3TC, lamivudine; AZT, zidovudine; HEU; HIV-exposed uninfected; HUU, HIV-unexposed uninfected; NVP, nevirapine.
Figure 2.
Figure 2.
Homeostatic model assessment-insulin resistance (HOMA-IR) comparing neonates with perinatal HIV exposure who are uninfected (HEU) versus those without perinatal exposure and uninfected (HUU) at birth (A) and 1 month of life (B). HOMA-IR among neonates HEU comparing tenofovir (TDF)/lamivudine or emtricitabine (XTC)/dolutegravir (DTG) versus TDF/XTC/efavirenz (EFV) at birth (C) and 1 month of life (D). Circles represent individual participant values and diamonds mean group values; boxes cover the interquartile range and the vertical line splitting boxes represent the median.
See this image and copyright information in PMC

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