Meeting NewsPerspective

Studies support use of integrase inhibitors in pregnant women with HIV

SEATTLE — Study data presented at CROI supported the use of integrase inhibitors in pregnant women with HIV. Both studies compared integrase inhibitors with efavirenz-based ART.

In a phase 4 multicenter, randomized, open-label trial, Mark H. Mirochnick, MD, professor of pediatrics and chief of the division of neonatology at Boston University, and colleagues compared the HIV virologic response, tolerability and safety of raltegravir- and efavirenz-based ART regimens when initiated during pregnancy.

From September 2013 through February 2018, they enrolled 408 pregnant women from sites in South America, Africa, Thailand and the United States, including 206 who received raltegravir (RAL) and 202 who received efavirenz (EFV), and followed them through 24 weeks post-delivery. Results showed that a larger proportion of women in the RAL group — mainly those enrolled at 28 weeks’ gestation or later — had a viral load of less than 200 copies/mL at delivery compared with those in the EFV group, 94% vs. 84% (P = .001). Additionally, a larger proportion of women in the RAL arm achieved a rapid and sustained reduction in viral load while staying on study drug through delivery, the researchers reported.

“What we found was consistent with what’s seen in nonpregnant adults: The HIV viral load went down more quickly with [raltegravir] than with [efavirenz] and for the women who enrolled later, that meant more of them had a lower viral load at the time of delivery in the [raltegravir] group,” Mirochnick said during a news conference at CROI.

“In both groups we had excellent tolerance with 97-plus percent continuing in assigned treatment until delivery. We learned that it’s safe to use an integrase inhibitor in pregnant women and that these drugs bring down the viral load.”

A second study by Saye Khoo, MBBS, MRCP, DTM&H, MD, professor of molecular and clinical pharmacology at the University of Liverpool, and colleagues found that dolutegravir (DTG) is well-tolerated and, compared with EFV, leads to more rapid virologic suppression before delivery when initiated in late pregnancy.

In the open-label trial, DolPHIN-2, Khoo and colleagues randomly assigned 268 pregnant women to DTG or EFV plus two nucleoside reverse-transcriptase inhibitors and measured viral load at baseline, 1 week and 4 weeks after initiation, then again at 36 weeks’ gestation and delivery, and 6 weeks post-partum to determine efficacy and occurrence of drug toxicity in mothers and infants.

According to the findings, a viral load of less than 50 copies/mL at delivery was significantly more likely in the DTG arm compared with the EFV arm, recorded in 74% vs. 43% of participants (adjusted RR = 1.66; 95% CI, 1.32-2.09). Khoo and colleagues reported that the trend was consistent across subgroups of baseline viral load, CD4 cell count, gestation at initiation, and other characteristics.

According to researchers, there were no significant differences between DTG and EFV groups in median gestational age at delivery — 39.9 weeks for both arms — or births at before 34 weeks (4.76% vs. 5.13%) or 37 weeks (16.67% vs. 15.38%) gestation.

“We were also able to learn about adverse outcomes,” Khoo said, noting four stillbirths, eight infant deaths (occurring in both arms) and three infant transmissions, all in the DTG arm. “Stillbirths related to maternal infections and obstetric complications. For transmissions, the speed at which the babies were tested, and low viral load pointed to these being in-utero transmissions.”

The researchers deduced that late presentation in pregnancy is associated with poor outcomes regardless of the drug.

“We did not think these bad outcomes were related to the drugs,” Khoo said. “They were related to the population we were seeing. Dolutegravir should be considered in these high-risk scenarios.” – by Caitlyn Stulpin

References:

Mirochnick M, et al. Abstract 39. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.

Kintu K, et al. Abstract 40. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.

Disclosures: Khoo reports receiving consulting or advisor fees from ViiV Healthcare and a research grant/grant pending from ViiV paid to his institution; Mirochnick reports receiving research grants/grants pending from Gilead Sciences, Merck and ViiV Healthcare.

SEATTLE — Study data presented at CROI supported the use of integrase inhibitors in pregnant women with HIV. Both studies compared integrase inhibitors with efavirenz-based ART.

In a phase 4 multicenter, randomized, open-label trial, Mark H. Mirochnick, MD, professor of pediatrics and chief of the division of neonatology at Boston University, and colleagues compared the HIV virologic response, tolerability and safety of raltegravir- and efavirenz-based ART regimens when initiated during pregnancy.

From September 2013 through February 2018, they enrolled 408 pregnant women from sites in South America, Africa, Thailand and the United States, including 206 who received raltegravir (RAL) and 202 who received efavirenz (EFV), and followed them through 24 weeks post-delivery. Results showed that a larger proportion of women in the RAL group — mainly those enrolled at 28 weeks’ gestation or later — had a viral load of less than 200 copies/mL at delivery compared with those in the EFV group, 94% vs. 84% (P = .001). Additionally, a larger proportion of women in the RAL arm achieved a rapid and sustained reduction in viral load while staying on study drug through delivery, the researchers reported.

“What we found was consistent with what’s seen in nonpregnant adults: The HIV viral load went down more quickly with [raltegravir] than with [efavirenz] and for the women who enrolled later, that meant more of them had a lower viral load at the time of delivery in the [raltegravir] group,” Mirochnick said during a news conference at CROI.

“In both groups we had excellent tolerance with 97-plus percent continuing in assigned treatment until delivery. We learned that it’s safe to use an integrase inhibitor in pregnant women and that these drugs bring down the viral load.”

A second study by Saye Khoo, MBBS, MRCP, DTM&H, MD, professor of molecular and clinical pharmacology at the University of Liverpool, and colleagues found that dolutegravir (DTG) is well-tolerated and, compared with EFV, leads to more rapid virologic suppression before delivery when initiated in late pregnancy.

In the open-label trial, DolPHIN-2, Khoo and colleagues randomly assigned 268 pregnant women to DTG or EFV plus two nucleoside reverse-transcriptase inhibitors and measured viral load at baseline, 1 week and 4 weeks after initiation, then again at 36 weeks’ gestation and delivery, and 6 weeks post-partum to determine efficacy and occurrence of drug toxicity in mothers and infants.

According to the findings, a viral load of less than 50 copies/mL at delivery was significantly more likely in the DTG arm compared with the EFV arm, recorded in 74% vs. 43% of participants (adjusted RR = 1.66; 95% CI, 1.32-2.09). Khoo and colleagues reported that the trend was consistent across subgroups of baseline viral load, CD4 cell count, gestation at initiation, and other characteristics.

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According to researchers, there were no significant differences between DTG and EFV groups in median gestational age at delivery — 39.9 weeks for both arms — or births at before 34 weeks (4.76% vs. 5.13%) or 37 weeks (16.67% vs. 15.38%) gestation.

“We were also able to learn about adverse outcomes,” Khoo said, noting four stillbirths, eight infant deaths (occurring in both arms) and three infant transmissions, all in the DTG arm. “Stillbirths related to maternal infections and obstetric complications. For transmissions, the speed at which the babies were tested, and low viral load pointed to these being in-utero transmissions.”

The researchers deduced that late presentation in pregnancy is associated with poor outcomes regardless of the drug.

“We did not think these bad outcomes were related to the drugs,” Khoo said. “They were related to the population we were seeing. Dolutegravir should be considered in these high-risk scenarios.” – by Caitlyn Stulpin

References:

Mirochnick M, et al. Abstract 39. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.

Kintu K, et al. Abstract 40. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.

Disclosures: Khoo reports receiving consulting or advisor fees from ViiV Healthcare and a research grant/grant pending from ViiV paid to his institution; Mirochnick reports receiving research grants/grants pending from Gilead Sciences, Merck and ViiV Healthcare.

    Perspective
    Elaine J. Abrams

    Elaine J. Abrams

    These two studies have parallels. They both evaluated integrase inhibitor regimens compared with what is the standard of care in most post parts of the world, an efavirenz-based treatment, in women who start treatment in late in pregnancy. These are women who often come in with more advanced disease or have been late to diagnoses and there is an urgency to rapidly reduce their viral load because we want to see an undetectable viral load at delivery, as that is correlated with risk of transmission to the baby. One study looked at dolutegravir and one looked at raltegravir with integrase inhibitors, which have been demonstrated to have a more rapid rate of viral decline with other similar treatments. As one expected, the integrase inhibitors were superior in both studies when compared with the standard of care. We have not had much research around integrase inhibitors during pregnancy, so these studies were quite important for giving us safety as well as efficacy data for this class of drugs in pregnancy. We must note, however, that drugs were not started until generally the second or third trimester, so it does not give us any information on exposure during the first trimester or conception.

    • Elaine J. Abrams, MD
    • Professor of epidemiology and pediatrics
      Columbia University

    Disclosures: Abrams reports no relevant financial disclosures.

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