Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

Abstract

Background Minimizing time to Human Immunodeficiency Virus (HIV) viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV ribonucleic acid (RNA) in nonpregnant adults. There is limited data in pregnant women. Objective We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing ART options. Study Design We conducted a retrospective cohort study of pregnant HIV-infected women in the U.S. from 2009 to 2015. We included women who initiated antiretroviral therapy (ART), intensified their regimen or switched to a new regimen due to detectable viremia (HIV RNA > 40c/mL) at ≥ 20 weeks gestation. Among women with a baseline HIV RNA permitting one-log reduction, we estimated time to one-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen versus other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. Results This study describes 101 HIV-infected pregnant women from 11 U.S. clinics. Seventy-five percent (76/101) women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. Thirty-nine percent (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting one-log reduction, the median time to one-log RNA reduction was 8 days [Interquartile Range (IQR): 7, 14] in the INSTI group versus 35 days [IQR: 20, 53] in the non-INSTI ART group (p<0.01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to one-log reduction was 7 days [IQR: 6, 10] in the INSTI group versus 11 days [IQR: 10, 14] in the non-INSTI group (p<0.01). Conclusion ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV-RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

“…A retrospective cohort analysis of 92 pregnant women with HIV showed more rapid viral suppression in those patients on an integrase inhibitor‐containing regimen vs . women on ART without an integrase inhibitor . Median time to viral load reduction by greater than 1 log 10 unit was 7 days in the integrase inhibitor‐containing ART arm and 35 days in the non‐integrase inhibitor ART arm ( P < 0.01).…”

Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy

“…DTG has also been shown to readily cross the blood-placenta barrier (8). Limited data are available to assess the placental transfer of EVG (28). Given the paucity of data and the increasing use of EVG and DTG in clinical obstetrical practice, including the use of EVG-COBI-TDF-FTC as a single antiretroviral regimen (and now EVG-COBI-TAF-FTC [Stribild; Gilead], where TAF is tenofovir alafenamide), our study is helpful in understanding transplacental passage of INSTIs.…”

Exposure to dolutegravir in pregnant women living with HIV in Central and Eastern Europe and neighboring countries — data from the ECEE Network Group

“…DTG-based therapy proved to be effective in achieving rapid viral suppression in pregnant women, even in late presenters and those with highly resistant virus, and in preventing mother-to-child transmission. This makes it an attractive choice in many settings including pregnancy [12,[18][19][20][21]. DTG is becoming a preferred antiretroviral drug in the region and reliable data are required urgently for such settings.…”