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Title: HIV infection in pregnant women : consequences for the child
Author: Ndirangu, J. N.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Currently, globally more than 3 million children under 15 years are living with HIV, 90% of whom live in sub-Saharan Africa (SSA); nearly all acquired infection through mother-to-child transmission. This thesis describes adverse pregnancy outcomes by maternal HIV status, the role of cell-associated and cell-free virus in postnatal mother-to-child transmission (MTCT) rates and the risk of not-breastfeeding on infant morbidity and mortality comparing infants of HIV infected and uninfected mothers. In infected children, the burden of HIV on hospitalization is evaluated. The last chapter quantifies the effect of prevention of MTCT (PMTCT) and maternal antiretroviral therapy (ART) on child mortality at population level. The data was from the Vertical Transmission Study (VTS) and the local district hospital database of admission and discharge diagnosis in rural northern KwaZulu-Natal, South Africa, an area with high HIV prevalence (40% in pregnant women). Additionally, a cohort of children on ART in the Hlabisa HIV treatment programme was used and linked to the Africa Centre demographic surveillance data which collects socio-demographic information tri-annually from approximately 90,000 people registered in 11,000 households since 2000. In the VTS of 2368 live births, 21.4% of infants were born preterm and 16.6% small-for-gestational age (SGA). HIV infected women were more likely to have SGA-infants than HIV uninfected women, but preterm delivery rates did not differ significantly by maternal HIV infection. Infant mortality increased with severity of SGA, but was similar for term and preterm infants. Exclusively-breastfed infants had lower incidences of diarrhoea and pneumonia events and days than infants who were not breastfed; a 2.4-fold increased risk of mortality was shown in infants who received no breastmilk compared to those who were ever breastfed. In a cohort nested in the VTS, cell-free (RNA) and cell-associated (DNA) virus levels in breastmilk were shown to be significantly associated with postnatal transmission; with cell-associated virus levels especially important in early (6 weeks) and cell-free virus levels in late (6 months) transmission. In a cohort of 660 HIV-positive children on ART, one in three children were hospitalised with TB after ART initiation. Additionally, TB was the main cause of hospital admissions in HIV-positive children (with or without ART) in this setting. In the surveillance area of 12,052 live births, under-5 mortality declined substantially, particularly infant mortality, which declined by 49% from 69 deaths per 1000 person-years of observation in 2000, to 35.5 in 2006. The, under-5 mortality decline coincided with ART scale-up: children born after the HIV programme was implemented had a 34-54% reduced risk of death compared to those born when there was no ART. Further, mortality in children of HIV-infected mothers on ART did not differ significantly from that of children of HIV-negative mothers (aHR 1.29; p=0.572). This work provides an extension of previous knowledge and understanding of the role of maternal HIV infection in child health in the early years of life and the recommendations will inform clinical management policy and practice in this and similar settings in SSA.
Supervisor: Newell, M. L. ; Thorne, C. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available