TY - JOUR
T1 - HIV-exposed uninfected infants in Zimbabwe
T2 - Insights into health outcomes in the pre-antiretroviral therapy era
AU - Evans, Ceri
AU - Humphrey, Jean H.
AU - Ntozini, Robert
AU - Prendergast, Andrew J.
N1 - Publisher Copyright:
© 2016 Evans, Humphrey, Ntozini and Prendergast.
PY - 2016/6/6
Y1 - 2016/6/6
N2 - The ZVITAMBO trial recruited 14,110 mother-infant pairs to a randomized controlled trial of vitamin A between 1997 and 2000, before the availability of antiretroviral therapy for HIV prophylaxis or treatment in Zimbabwe. The HIV status of mothers and infants was well characterized through 1-2 years of follow-up, leading to the largest cohort to date of HIV-exposed uninfected (HEU) infants (n = 3135), with a suitable comparison group of HIV-unexposed infants (n = 9510). Here, we draw on 10 years of published findings from the ZVITAMBO trial. HEU infants had increased morbidity compared to HIV-unexposed infants, with 50% more hospitalizations in the neonatal period and 30% more sick clinic visits during infancy, particularly for skin infections, lower respiratory tract infections, and oral thrush. HEU children had 3.9-fold and 2.0-fold higher mortality than HIV-unexposed children during the first and second years of life, respectively, most commonly due to acute respiratory infections, diarrhea/dysentery, malnutrition, sepsis, and meningitis. Infant morbidity and mortality were strongly related to maternal HIV disease severity, and increased morbidity remained until maternal CD4 counts were > 800 cells/μL. HEU infants were more likely to be premature and small-for-gestational age than HIV-unexposed infants, and had more postnatal growth failure. Here, we propose a conceptual framework to explain the increased risk of infectious morbidity, mortality, and growth failure among HEU infants, hypothesizing that immune activation and inflammation are key drivers of both infection susceptibility and growth failure. Future studies should further dissect the causes of infection susceptibility and growth failure anddetermine the impact of ART and cotrimoxazole on outcomes of this vulnerable group of infants in the current era.
AB - The ZVITAMBO trial recruited 14,110 mother-infant pairs to a randomized controlled trial of vitamin A between 1997 and 2000, before the availability of antiretroviral therapy for HIV prophylaxis or treatment in Zimbabwe. The HIV status of mothers and infants was well characterized through 1-2 years of follow-up, leading to the largest cohort to date of HIV-exposed uninfected (HEU) infants (n = 3135), with a suitable comparison group of HIV-unexposed infants (n = 9510). Here, we draw on 10 years of published findings from the ZVITAMBO trial. HEU infants had increased morbidity compared to HIV-unexposed infants, with 50% more hospitalizations in the neonatal period and 30% more sick clinic visits during infancy, particularly for skin infections, lower respiratory tract infections, and oral thrush. HEU children had 3.9-fold and 2.0-fold higher mortality than HIV-unexposed children during the first and second years of life, respectively, most commonly due to acute respiratory infections, diarrhea/dysentery, malnutrition, sepsis, and meningitis. Infant morbidity and mortality were strongly related to maternal HIV disease severity, and increased morbidity remained until maternal CD4 counts were > 800 cells/μL. HEU infants were more likely to be premature and small-for-gestational age than HIV-unexposed infants, and had more postnatal growth failure. Here, we propose a conceptual framework to explain the increased risk of infectious morbidity, mortality, and growth failure among HEU infants, hypothesizing that immune activation and inflammation are key drivers of both infection susceptibility and growth failure. Future studies should further dissect the causes of infection susceptibility and growth failure anddetermine the impact of ART and cotrimoxazole on outcomes of this vulnerable group of infants in the current era.
KW - Africa
KW - Breast-feeding
KW - HIV exposure
KW - Immune activation
KW - Infant
KW - Inflammation
KW - Zimbabwe
UR - http://www.scopus.com/inward/record.url?scp=84977516762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84977516762&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2016.00190
DO - 10.3389/fimmu.2016.00190
M3 - Article
C2 - 27375613
AN - SCOPUS:84977516762
SN - 1664-3224
VL - 7
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JUN
M1 - 190
ER -