| Summary: | This thesis aims to investigate immunological and virological markers of HIV infection during pregnancy and to inform understanding of the impact of antenatal antiretroviral therapy (ART) regimens on such markers, using data from the European Collaborative Study (ECS). Since 1986, over 7,000 HIV infected pregnant women have been enrolled from 23 centres in 10 countries. Maternal information collected included timing and type of treatment regimen, repeated measurements on maternal CD4 counts and viral load (since 1987) and socio-demographic variables. Repeated HIV RNA measurements over pregnancy in over 300 untreated women were examined using linear mixed effects (LME) models. Immunological (CD4) and virological changes over pregnancy in 162 women receiving highly-active ART (HAART) at conception and throughout pregnancy were examined with a piecewise LME model, using a conditional likelihood approach to account for left-censored measurements. A bivariate LME model was used to assess the correlation between the two markers. Viral response to initial HAART regimens in 240 ART-naive pregnant women was determined using interval censored regression, with a propensity score to reduce treatment allocation bias. A Cox regression model was used to assess the effect of HAART on risk of premature delivery, treating elective caesarean section deliveries as right-censored outcomes. HIV RNA viral load was estimated to decrease over the second and third trimesters of pregnancy in untreated and treated women. Differences in levels of HIV RNA viral load and CD4 count by race and history of injecting drug use were identified. The rate of achieving undetectable viral load was greater for women initiating on nevirapine- containing HAART than for women on protease inhibitor-based HAART. There was no evidence of an increased risk of birth defects or prematurity associated with type or timing of HAART. These findings contribute to the evidence-base for management and understanding of HIV infection in pregnancy.
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