Effectiveness and safety of integrase inhibitors in HIV-infected pregnant women followed up in the Madrid Cohort

Background The risk of HIV-1 mother-to-child transmission (MTCT) is associated mainly with the gestational age at which antiretroviral therapy (AT) begins and HIV-1-RNA viral load (VL) at delivery. The importance of achieving virological supression during pregnancy, has led to an increased use of integrase inhibitors (INIs) in risky conditions. Our objective was to assess the safety and effectiveness in Madrid-Cohort of mothers-children exposed to INIs during pregnancy. Methods Retrospective, multicentric, observational, cohort study, of HIV-1-infected pregnant women exposed to INIs during pregnancy and their infants, from 2000 to 2017, from the nine public hospitals belonging to the Madrid Cohort. Maternal demographic characteristics, clinical data, HIV-1 infection features, AT regimens and changes of treatment during pregnancy were recorded. Blood count, biochemistry panel, HIV-1 VL and CD4+ lymphocyte counts/percentage at first trimester and at the last one near delivery were also collected. Results Sixty seven pregnant women exposed to INIs from the Madrid cohort (n: 1423) and their 68 children were identified (17.6% premature). Neonatal prophylaxis consited mostly on zidovudine (AZT) monotherapy, followed by combined prophylaxis with ‘triple therapy’. There were no cases of MTCT. Twenty women were diagnosed with HIV-1 in the current pregnancy. Of 43 women with AT before pregnancy, 65% received INI before conception. Raltegravir was the most commonly used (80.5%). The median lenght with INI at delivery was 148 days [interquartile rang (IR): 29-251]. Median CD4+ lymphocyte count increased from 428 cells/mL (IR: 310-642) in first trimester to 636 cells/mL (IR: 408-818) in the third. There was a statistically significant increase (p=0.02) of mothers with undetectable VL at delivery compared with first trimester. INIs were well tolerated, without any relevant adverse effect notification. There was no case of discontinued medication due to intolerance or toxicity. 11,7% of children had minor birth defects and one patient had ventricular septal defect without hemodynamic compromise. All of them evolved favourably. Conclusions INI seems safe and effective in prevention of MTCT. Antiretroviral regimens during pregnancy that include INI are increasingly being used. Our findings support the use of INI as intensification in pregnant women at high risk of MTCT.