Short Communication: Use of Raltegravir in Late-Presenting HIV-Infected Pregnant Women

Abstract

The risk of HIV-1 mother-to-child transmission (MTCT) is clearly correlated with the maternal HIV cell-free viral load (VL) at delivery. Preventing MTCT in late-presenting (after 28 weeks) HIV-infected pregnant women remains a clinical challenge, and ensuring a rapid decrease of maternal VL is an important preventive strategy. Raltegravir (RGV) has a higher first and second phase viral decay rate, has a high placental transfer, with a potential preloading effect for neonate, and demonstrates effective accumulation in cervicovaginal secretions. We report 14 cases in which RGV was used late in pregnancy for HIV-1 MTCT prophylaxis. All women were RGV naive and the prophylaxis regimens included RGV plus at least two other antiretroviral agents. At RGV initiation, the median gestational age was 36 weeks (range 34-38) and the median maternal plasma HIV-1 RNA viral load was 35,364 copies/ml (range 636-391,535). At delivery, the median gestational age was 38 weeks (range 37-40). The median exposure time to RGV was 17 days (range 7-32), with a mean maternal VL decay of 2.6 log. At delivery, seven women had undetectable ( < 50 copies/ml) VL, four had between 64 and 457 copies/ml, and in three VL was not available. All but one infant's HIV-RNA tests were negative at 1 and 3 months (one case of in utero MTCT). Raltegravir-containing antiretroviral regimens induced a rapid HIV-RNA decline in maternal VL at delivery, and were safe and effective in preventing MTCT for late-presenting, HIV-infected women.

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

“…This study supports previously published case reports of rapid decline in HIV-1 viral load after treatment with INSTI-containing regimens. 8,9,11,12 All of the observed ART regimens were effective in decreasing HIV viral load in a relatively short time period, but the addition of an integrase inhibitor suppressed viral load more quickly. This is consistent with prior literature describing the effect of INSTI-based ART in pregnancy, however, a strength of our study is that we compared INSTI- and non-INSTI-containing ART directly.…”

“…This is consistent with prior literature describing the effect of INSTI-based ART in pregnancy, however, a strength of our study is that we compared INSTI- and non-INSTI-containing ART directly. 8,9,11–14 Additionally, we describe the clinical practice of using regimens that did not fall under 1 st line recommended maternal treatment at the time of the study. 1 According to these data, pregnant HIV-infected women are prescribed newer potent ART options or regimens that are convenient once-a-day options, likely in order to promote adherence.…”

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

“…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). In a second retrospective study of 14 women, raltegravir was either initiated as part of a cART regimen in nine antiretroviral‐naïve women or added to an existing antiretroviral regimen in five women who had conceived on cART but had persistent viraemia . Raltegravir was initiated at a gestational age of 34 weeks or later.…”

BritishHIVAssociation guidelines for the management ofHIVinfection in pregnant women 2012 (2014 interim review)

“…efavirenz) or in combination with other antiretrovirals . It is important to note that no adequate or well‐controlled studies of raltegravir have been conducted in pregnant women; however, case reports and small case series reporting rapid HIV decay with raltegravir‐based regimens are appearing in the medical literature [150–154]. Pharmacokinetic data presented in Recommendation 5.2.4 indicate that no dose change is required in the third trimester.…”