Atazanavir and darunavir in pregnant women with HIV: Evaluation of laboratory and clinical outcomes from an observational national study

Background: Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparativedata in pregnant women are limited.We assessed the safety and activity profile of these two drugs in pregnancyusing data from a national observational study.Methods: Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measuresand main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatalgestational age-adjusted birthweight Z-score).Results: Final analysis included 500 pregnancies with either atazanavir (n"409) or darunavir (n"91) exposure.No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA,haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the twogroups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides(median 235.5 versus 179 mg/dL; P"0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03versus 3.27; P"0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54versus 0.32 mg/dL; P<0.001).Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelinesshowed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in termsof main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribingphysicians might prefer either drug in some particular situations where the different impacts of treatment onlipid profile and bilirubin may have clinical relevance

Continuum of care among HIV-1 positive patients in a single center in Italy (2007–2017)

Filippo Lagi,1 Seble Tekle Kiros,1 Irene Campolmi,1 Susanna Giachè,1 Pier Giorgio Rogasi,2 Marcello Mazzetti,2 Filippo Bartalesi,2 Michele Trotta,2 Patrizia Nizzoli,3 Alessandro Bartoloni,1,2 Gaetana Sterrantino2 1Infectious Disease Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 2Infectious and Tropical Disease Unit, Azienda Ospedaliero – Universitaria Careggi, Florence, Italy; 3Department of Pharmaceuticals, USL Toscana Centro, Florence, Italy Aim: This study aimed to determine rates of retention in care, viral suppression, and use of antiretroviral therapy (ART) and identify risk factors for loss to follow-up (FU) in an adult cohort from a tertiary teaching hospital in Florence, Italy. Methods: We included all newly diagnosed HIV-infected patients aged >18 years who were linked to our clinic from July 2007 to December 2015. On July 31, 2017, we evaluated the proportion of patients retained in care, on ART, and having HIV RNA <50 copies/mL. We assessed predictors of loss to FU through univariate and multivariate analyses. Results: We included 423 patients. By July 2017, 23 (5.5%) patients died, 25 (5.9%) moved to a different center, and 64 (15.1%) were lost to follow-up. Among the remaining 311 patients (73.5%), 96.5% were on ART and 95% had HIV RNA <50 copies/mL. After adjustment for sex, age at diagnosis, origin, and risk of transmission, our results showed a lower retention rate in those not on ART at the end of the follow-up (adjusted HR [aHR]: 10.33, 95% CI 5.80–18.40, P<0.001), non-Italians (aHR: 1.69, 95% CI: 0.99–2.89, P=0.054) and <35 years old (aHR: 1.85; 95% CI 1.04–3.30, P=0.037). Conclusion: In our hospital in Florence, we found a gap in retention in care among foreigners, people <35 years old, and those who were not in treatment at the end of the follow-up. The results of this study may help to identify opportunities for appropriate future interventions. Keywords: HIV-1, continuum of care, retention in care, Italy, 90-90-90 target, predictors associated to loss to follow-u

Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir?

Background: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options. Objectives: The aim of this article was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease. Sources: Two databases (PubMed and ClinicalTrial.gov) were reviewed. Content: Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort. Implications: Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the 'off label' use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study

Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir?

Background: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options. Objectives: The aim of this article was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease. Sources: Two databases (PubMed and ClinicalTrial.gov) were reviewed. Content: Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort. Implications: Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the ‘off label’ use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study