Unveiling the basis of antiretroviral therapy-induced osteopenia: the effects of Dolutegravir, Darunavir and Atazanavir on osteogenesis.

Osteopenia is frequent in HIV-infected patients treated with antiretroviral therapy (ART) and has been linked to increased osteoclastogenesis. Little is known about the effects of ART on osteogenesis. We investigated the effect on human mesenchymal stem cells (hMSC) and osteoblasts of Darunavir and Dolutegravir, the most highly used as anchor drugs within a three-drug regimen, and Atazanavir, which was widely utilized in the past. We found that Atazanavir and Dolutegravir delay the osteogenic differentiation of hMSC, impair the activity of osteoblasts and inhibit their conversion into osteocytes, whereas Darunavir exerts no effect. Atazanavir and Dolutegravir impair osteogenesis. It is essential to diagnose impaired osteogenesis early and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients, putting it in the context of a correct antiretroviral combination.

Cazzaniga A ，Scrimieri R ，Galli M ，Maier J ，Rusconi S ... -  《-》

Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States.

Data on the effectiveness and safety of dolutegravir-based antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1) infection in pregnancy as compared with other ART regimens commonly used in the United States and Europe, particularly when initiated before conception, are limited. We conducted a study involving pregnancies in persons with HIV-1 infection in the Pediatric HIV/AIDS Cohort Study whose initial ART in pregnancy included dolutegravir, atazanavir-ritonavir, darunavir-ritonavir, oral rilpivirine, raltegravir, or elvitegravir-cobicistat. Viral suppression at delivery and the risks of infants being born preterm, having low birth weight, and being small for gestational age were compared between each non-dolutegravir-based ART regimen and dolutegravir-based ART. Supplementary analyses that included participants in the Swiss Mother and Child HIV Cohort Study were conducted to improve the precision of our results. Of the pregnancies in the study, 120 were in participants who received dolutegravir, 464 in those who received atazanavir-ritonavir, 185 in those who received darunavir-ritonavir, 243 in those who received rilpivirine, 86 in those who received raltegravir, and 159 in those who received elvitegravir-cobicistat. The median age at conception was 29 years; 51% of the pregnancies were in participants who started ART before conception. Viral suppression was present at delivery in 96.7% of the pregnancies in participants who received dolutegravir; corresponding percentages were 84.0% for atazanavir-ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir-cobicistat (adjusted risk differences vs. dolutegravir, -13.0 percentage points [95% confidence interval {CI}, -17.0 to -6.1], -17.0 percentage points [95% CI, -27.0 to -2.4], and -7.0 percentage points [95% CI, -13.3 to -0.0], respectively). The observed risks of preterm birth were 13.6 to 17.6%. Adjusted risks of infants being born preterm, having low birth weight, or being small for gestational age did not differ substantially between non-dolutegravir-based ART and dolutegravir. Results of supplementary analyses were similar. Atazanavir-ritonavir and raltegravir were associated with less frequent viral suppression at delivery than dolutegravir. No clear differences in adverse birth outcomes were observed with dolutegravir-based ART as compared with non-dolutegravir-based ART, although samples were small. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Patel K ，Huo Y ，Jao J ，Powis KM ，Williams PL ，Kacanek D ，Yee LM ，Chadwick EG ，Shiau S ，Jacobson DL ，Brummel SS ，Sultan-Beyer L ，Kahlert CR ，Zash R ，Seage GR 3rd ，Pediatric HIV/AIDS Cohort Study ，Swiss Mother and Child HIV Cohort Study ... -  《-》

Efficacy and tolerability of lamivudine plus dolutegravir compared with lamivudine plus boosted PIs in HIV-1 positive individuals with virologic suppression: a retrospective study from the clinical practice.

Borghetti A ，Lombardi F ，Gagliardini R ，Baldin G ，Ciccullo A ，Moschese D ，Emiliozzi A ，Belmonti S ，Lamonica S ，Montagnani F ，Visconti E ，De Luca A ，Di Giambenedetto S ... -  《BMC INFECTIOUS DISEASES》

HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells.

Auclair M ，Guénantin AC ，Fellahi S ，Garcia M ，Capeau J ... -  《PLoS One》

Short-cycle therapy (5 days on/2 days off) with a lamivudine + dolutegravir regimen in a cohort of virologically suppressed patients with HIV infection.

Lanzafame M ，Lattuada E ，Gottardo R ，Piacentini D ，Be G ，Razzaboni E ，Cattaneo P ，Luise D ，Vento S ... -  《-》