Metabolic Complications of in utero Maternal HIV and Antiretroviral Exposure in HIV-exposed Infants

Jao, Jennifer; Abrams, Elaine J.

doi:10.1097/inf.0000000000000224

Cited by 40 publications

(33 citation statements)

References 88 publications

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“…For example, studies in rhesus macaques exposed in utero to high doses of tenofovir showed reduced levels of insulin-like growth factor-1 (IGF-1) and reduced intrauterine growth. 7 …”

Section: Discussionmentioning

confidence: 99%

“…7 In a Canadian cohort of HEU infants exposed to cART in utero plasma lactate levels were increased during the first 6 months of life, 25 possibly as a consequence of mitochondrial toxicity that may persist for several years. 26 Many pathways of intermediary metabolism, including fatty acid oxidation, organic acid metabolism and amino acid metabolism, depend on normal oxidative phosphorylation and could therefore be affected by mitochondrial toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…4–7 A study from Botswana showed that exposure to cART during pregnancy (initiated before conceptionor started during pregnancy) was associated with low birth weight and other adverse birth outcomes compared with ZDV monotherapy started later during pregnancy. 8 Growth trajectories after birth are also of concern.…”

mentioning

confidence: 99%

“…9 A recent systematic literature review concluded that it remains unknown whether in utero exposure to ARVs has alasting impact on infant growth. 7 …”

mentioning

confidence: 99%

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In Utero Exposure to Antiretroviral Drugs

Keiser

Zwahlen

et al. 2016

Pediatric Infectious Disease Journal

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Context There are concerns about the effects of in utero exposure to antiretroviral drugs (ARVs) on the development of HIV exposed but uninfected (HEU) children. Objectives To evaluate whether in utero exposure to ARVs is associated with lower birth weight/height and reduced growth during the first two years of life. Design Cohort study of HEU infants. Setting Tertiary children's hospital in Rio de Janeiro, Brazil. Study population HEU infants born 1996-2010. Main outcome measures Weight measured by mechanical scale, height measured by measuring board. Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) were calculated. We modeled trajectories by mixed-effects models and adjusted for mother's age, CD4 cell count, viral load, year of birth and family income. Results A total of 588 HEU infants were included of whom 155 (26%) were not exposed to ARVs, 114 (19%) were exposed early (first trimester) and 319 (54%) later. WAZ were lower among infants exposed early compared to infants exposed later: adjusted differences were −0.52 (95% CI −0.99 to −0.04, P=0.02) at birth and −0.22 (95% CI −0.47 to 0.04, P=0.10) during follow-up. LAZ were lower during follow-up: −0.35 (95% CI −0.63 to −0.08, P=0.01). There were no differences in WLZ scores. Z-scores of infants exposed late during pregnancy were similar to unexposed infants. Conclusions In HEU children early exposure to ARVs was associated with lower WAZ at birth and lower LAZ up to 2 years of life. Growth of HEU children needs to be monitored closely.

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“…For example, studies in rhesus macaques exposed in utero to high doses of tenofovir showed reduced levels of insulin-like growth factor-1 (IGF-1) and reduced intrauterine growth. 7 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…9 A recent systematic literature review concluded that it remains unknown whether in utero exposure to ARVs has alasting impact on infant growth. 7 …”

mentioning

confidence: 99%

See 2 more Smart Citations

In Utero Exposure to Antiretroviral Drugs

Keiser

Zwahlen

et al. 2016

Pediatric Infectious Disease Journal

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“…Therefore, to avert the potential for major physical harm such as in the case of diethylstilboestrol exposure, disclosure is necessary in order to properly monitor HEU individuals into adulthood. Second, one could argue that in addition to childhood malignancies [16,17,23,36,37], there are a myriad of concerning data already surrounding malignancies as well as the mitochondrial [38–44], mental [45–47], bone [48–51], cardiovascular [52–54] and metabolic [55–57] health in HEU children as described herein.…”

Section: Discussionmentioning

confidence: 99%

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Jao

Hazra

Mellins

et al. 2016

Journal of the International AIDS Society

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IntroductionThe tremendous success of antiretroviral therapy has resulted in a diminishing population of perinatally HIV-infected children on the one hand and a mounting number of HIV-exposed uninfected (HEU) children on the other. As the oldest of these HEU children are reaching adolescence, questions have emerged surrounding the implications of HEU status disclosure to these adolescents. This article outlines the arguments for and against disclosure of a child's HEU status.DiscussionDisclosure of a child's HEU status, by definition, requires disclosure of maternal HIV status. It is necessary to weigh the benefits and harms which could occur with disclosure in each of the following domains: psychosocial impact, long-term physical health of the HEU individual and the public health impact. Does disclosure improve or worsen the psychological health of the HEU individual and extended family unit? Do present data on the long-term safety of in utero HIV/ARV exposure reveal potential health risks which merit disclosure to the HEU adolescent? What research and public health programmes or systems need to be in place to afford monitoring of HEU individuals and which, if any, of these require disclosure?ConclusionsAt present, it is not clear that there is sufficient evidence on whether long-term adverse effects are associated with in utero HIV/ARV exposures, making it difficult to mandate universal disclosure. However, as more countries adopt electronic medical record systems, the HEU status of an individual should be an important piece of the health record which follows the infant not only through childhood and adolescence but also adulthood. Clinicians and researchers should continue to approach the dialogue around mother–child disclosure with sensitivity and a cogent consideration of the evolving risks and benefits as new information becomes available while also working to maintain documentation of an individual's perinatal HIV/ARV exposures as a vital part of his/her medical records. As more long-term adult safety data on in utero HIV/ARV exposures become available these decisions may become clearer, but at this time, they remain complex and multi-faceted.

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