Preconception use of cART by HIV-positive pregnant women increases the risk of infants being born small for gestational age.

BACKGROUND: The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands. MATERIALS AND METHODS: We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery. RESULTS: A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03-1.77, p = 0.03). The risk for SGA was highest in women who started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with women who initiated PI-based cART during pregnancy. While the association of preterm delivery and preconception cART was significant in univariate analysis, on multivariate analysis only a non-significant trend was observed (OR 1.39, 95% CI 0.94-1.92, p = 0.06) in women who had started cART before compared to after conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95% CI 0.94-1.92, p = 0.11) was not significantly increased in women who had started cART prior to conception compared to after conception. CONCLUSION: In our cohort of pregnant HIV-positive women, the use of cART prior to conception, most notably a PI-based regimen, was associated with intrauterine growth restriction resulting in SGA. Data showed a non-significant trend in the risk of PTD associated with preconception use of cART compared to its use after conception. More studies are needed with regard to the mechanisms taking place in the placenta during fetal growth in pregnant HIV-positive women using cART. It will only be with this knowledge that we can begin to understand the potential impact of HIV and cART on the fetus, in order to be able to determine the optimal individualised drug regimen for HIV-infected women of childbearing age.

[Late diagnosis of HIV positive patients in Rotterdam, the Netherlands: risk factors and missed opportunities]. / Late diagnose van hiv-patiënten in Rotterdam: risicofactoren en gemiste kansen.

OBJECTIVE: To determine the percentage of patients in whom the diagnosis 'HIV infection' was made late, which factors are associated with an increased risk of a late HIV diagnosis, and if there are opportunities for an earlier diagnosis. DESIGN: Retrospective analysis. METHOD: We included all HIV positive patients who were treated at the Erasmus Medical Center Rotterdam in the period January 1996-March 2012. We divided these patients into two groups: patients with a timely diagnosis and patients with a late diagnosis (CD4+ T cell count < 350/mm3). We performed a structured interview in patients who were diagnosed in the period January 2009-March 2012. To determine possible risk factors for a late diagnosis we used univariate and multivariate analyses. RESULTS: A late diagnosis 'HIV infection' was made in 59% of the 2256 patients. Independent patient characteristics associated with a late diagnosis were heterosexual transmission (odds ratio (OR): 1.87; 95% CI: 1.44-2.43; p < 0.001), age > 50 years (OR: 1.73; 95% CI: 1.28-2.34; p < 0.001), and a Sub-Saharan African (OR: 1.66; 95% CI: 1.02-2.71; p = 0.043) or Asian origin (OR: 2.31; 95% CI: 1.20-4.43; p = 0.012). The interviews showed that more than 75% of patients with a late HIV diagnosis were already known with a risk factor for HIV, according to the STD practice guideline from the Dutch College of General Practitioners. CONCLUSION: In the past 15 years, 59% of HIV positive patients in Rotterdam presented late. This mainly concerned patients older than 50 years and immigrants originating from HIV endemic areas. It is important to prevent a late diagnosis, as this can lead to poorer response to combination antiretroviral therapy and higher mortality.

Hcv coinfection, an important risk factor for hepatotoxicity in pregnant women starting antiretroviral therapy.

OBJECTIVES: This retrospective cohort study evaluated the risk of hepatotoxicity in HIV-1 positive pregnant and non-pregnant women starting combined ART. METHODS: Data were used from the ATHENA observational cohort. The study population consisted of HIV-1 infected, therapy naïve, pregnant and non-pregnant women, followed between January 1997 and February 2008. Demographic, treatment and pregnancy related data were collected. Risk of hepatotoxicity was determined using univariate and multivariate logistic regression. Analyses were adjusted for age, region of origin, baseline HIV-RNA levels and CD4 cell counts, cART regimen and hepatitis B and C coinfection. ALT and AST values of more than 5 times ULN were considered as hepatotoxicity. RESULTS: Four-hundred and twenty-five pregnant and 1121 non-pregnant women were included. Independent risk factors of hepatotoxicity in all women were the presence of detectable HCV RNA (OR 5.48, 95% CI 2.25-13.38, p<0.001) and NVP use (OR 2.63, 95% CI 1.54-4.55, p<0.001). Stratified for pregnancy, the adjusted risk of hepatotoxicity was significantly associated with HCV coinfection only during pregnancy (OR 23.53, 95% CI 4.69-118.01, p<0.001). NVP use is related to hepatotoxicity in pregnant (OR 5.26, 95% CI 1.61-16.67, p<0.005) as well as in non-pregnant women (OR 2.13, 95% CI 1.11-4.00, p=0.02). CONCLUSION: HCV coinfection and NVP use are associated with a higher risk of cART induced hepatotoxicity in pregnant women.

Current and future applications of dried blood spots in viral disease management.

Almost five decades after their first application in diagnostics, dried blood spot (DBS) cards remain to be of key interest in many research areas and clinical applications. The advantages of sample stability during transport and storage, can now be combined with the high sensitivity of novel diagnostic techniques for the measurement and analysis of nucleic acids, proteins and small molecules which may overcome the limitations of the small samples sizes in DBS cards. Here we present a survey of the literature on the use of DBS cards for diagnosis, monitoring and epidemiological studies of virus infections other than HIV, including CMV, HBV, HCV, HAV, HEV, HTLV, EBV, HSV, measles-, rubella- and dengue-virus. The minimal invasiveness of sampling and the relative ease of handling and storing DBS cards is expected to offer additional opportunities to measure and analyze biomarkers of viral disease in resource poor settings or when limited amount of blood can be obtained. Large retrospective studies of virus infections in newborns using stored DBS cards have already been undertaken for screening of congenital infections. In addition, DBS cards have been used prospectively for prevalence studies, outbreak surveillance, mass screening for viral infections, follow-up of chronic infection and its treatment in resource-limited areas. We do not expect that current wet sampling techniques of plasma or serum will be replaced by DBS sampling but it allows extension of sampling in persons and settings that are currently difficult to access or that lack suitable storage facilities. In conclusion, DBS card sampling and storage will aid adequate outbreak management of existing and emerging viral diseases.