A meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children

Brennan, Alana T.; Bonawitz, Rachael; Gill, Christopher J.; Thea, Donald M.; Kleinman, Mary B.; Useem, Johanna; Garrison, Lindsey; Ceccarelli, Rachel; Udokwu, Chinenye; Long, Lawrence; Fox, Matthew P.

doi:10.1097/qad.0000000000001211

Cited by 123 publications

(96 citation statements)

References 59 publications

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“…Efforts to increase retention and HIV testing could improve the diagnosis of HIV-infected children and their access to ART. Better retention could also improve poor health outcomes among HIV-exposed uninfected children [28]. Interventions to improve retention should address possible drivers of loss to follow-up, including non-disclosure of HIV status, low socio-economic status of parents, low maternal education, lack of support from family members and partners and fear of stigma [29–31].…”

Section: Discussionmentioning

confidence: 99%

HIV transmission and retention in care among HIV‐exposed children enrolled in Malawi's prevention of mother‐to‐child transmission programme

Haas

Oosterhout

Tenthani

et al. 2017

Journal of the International AIDS Society

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Introduction: In Malawi, HIV-infected pregnant and breastfeeding women are offered lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage (Option B+). Their HIV-exposed children are enrolled in the national prevention of mother-to-child transmission (PMTCT) programme, but many are lost to follow-up. We estimated the cumulative incidence of vertical HIV transmission, taking loss to follow-up into account. Methods: We abstracted data from HIV-exposed children enrolled into care between September 2011 and June 2014 from patient records at 21 health facilities in central and southern Malawi. We used competing risk models to estimate the probability of loss to follow-up, death, ART initiation and discharge, and used pooled logistic regression and inverse probability of censoring weighting to estimate the vertical HIV transmission risk. Results: A total of 11,285 children were included; 9285 (82%) were born to women who initiated ART during pregnancy. At age 30 months, an estimated 57.9% (95% CI 56.6–59.2) of children were lost to follow-up, 0.8% (0.6–1.0) had died, 2.6% (2.3–3.0) initiated ART, 36.5% (35.2–37.9) were discharged HIV-negative and 2.2% (1.5–2.8) continued follow-up. We estimated that 5.3% (95% CI 4.7–5.9) of the children who enrolled were HIV-infected by the age of 30 months, but only about half of these children (2.6%; 95% CI 2.3–2.9) were diagnosed. Conclusions: Confirmed mother-to-child transmission rates were low, but due to poor retention only about half of HIV-infected children were diagnosed. Tracing of children lost to follow-up and HIV testing in outpatient clinics should be scaled up to ensure that all HIV-positive children have access to early ART.

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Section: Discussionmentioning

confidence: 99%

HIV transmission and retention in care among HIV‐exposed children enrolled in Malawi's prevention of mother‐to‐child transmission programme

Haas

Oosterhout

Tenthani

et al. 2017

Journal of the International AIDS Society

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“…Consequently, there is little focus within countries on measuring outcomes in HEU children beyond prevention of vertical HIV infection. While the bigger picture of improving health and well-being for all children must be kept in mind, and one group should not be prioritized to the detriment of the other, the evidence is mounting that HEU children experience excess morbidity and mortality (21, 22). There is a pressing need for clinicians, program implementers, researchers, policy makers, and HIV-affected families to form an organized community of HEU child advocates that can coordinate placing HEU children in a more prominent position on the global HIV research and monitoring agenda.…”

Section: Resultsmentioning

confidence: 99%

Optimizing Research Methods to Understand HIV-Exposed Uninfected Infant and Child Morbidity: Report of the Second HEU Infant and Child Workshop

2016

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“…Additionally, HEU children appear to experience immune system differences, an increase in infectious disease severity and greater mortality compared to HIV-unexposed children [69–71]. Early studies suggested an association with advanced maternal HIV disease [72, 73], however more recent evidence indicates that these findings persist despite improving maternal health and safer breastfeeding in the context of maternal ART [71, 74, 75].…”

Section: Considerations For In Utero Antiretroviral Exposed Childrenmentioning

confidence: 99%

“…Early studies suggested an association with advanced maternal HIV disease [72, 73], however more recent evidence indicates that these findings persist despite improving maternal health and safer breastfeeding in the context of maternal ART [71, 74, 75]. The role of specific ARVs or ART more generally in ameliorating or exacerbating this increased morbidity and mortality is unclear and further work to understand the risks to HEU child health in the current context of new ART regimens is required [76].…”

Section: Considerations For In Utero Antiretroviral Exposed Childrenmentioning

confidence: 99%

Toward a universal antiretroviral regimen

Slogrove

Clayden²,

Abrams

2017

Current Opinion in HIV and AIDS

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Purpose of review As optimized antiretroviral therapy (ART) regimens are prepared for introduction in low and middle income countries (LMIC), we consider the current evidence related to dosing, efficacy and safety during pregnancy and breastfeeding of next generation first- and second-line ART regimens proposed for imminent introduction in the global marketplace. Recent findings Pregnancy pharmacokinetic considerations include potentially insufficient efavirenz exposure if dosed at 400mg/day, the need for twice daily darunavir dosing and the paucity of data related to tenofovir alafenamide and dolutegravir dosing, safety and efficacy. Increasingly evidence suggests an association with adverse birth outcomes, particularly in women conceiving on ART, and with varying risk by drug and drug combination. Clinical trials and studies are in progress or planned that aim to determine dosing, safety and efficacy of several new antiretrovirals. Summary Having a universal, highly potent and safe ART regimen for all individuals living with HIV in LMIC including pregnant women is clearly the most beneficial strategy to keep mothers alive and healthy and to prevent transmission of HIV to their children. It will have to be determined whether use of this next generation of optimized antiretrovirals will also optimize health outcomes of pregnant women and their children.

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A meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children

Abstract: We show a consistent increase risk of mortality for HEU vs. HUU infants and children. Longitudinal research is needed to elucidate underlying mechanisms, such as maternal and infant health status and breast feeding practices, which may help explain these differences in mortality.

Cited by 123 publications

References 59 publications

HIV transmission and retention in care among HIV‐exposed children enrolled in Malawi's prevention of mother‐to‐child transmission programme

HIV transmission and retention in care among HIV‐exposed children enrolled in Malawi's prevention of mother‐to‐child transmission programme

Optimizing Research Methods to Understand HIV-Exposed Uninfected Infant and Child Morbidity: Report of the Second HEU Infant and Child Workshop

Toward a universal antiretroviral regimen

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