Rapid HIV-RNA decline following addition of raltegravir and tenofovir to ongoing highly active antiretroviral therapy in a woman presenting with high-level HIV viraemia at week 38 of pregnancy

Pinnetti, Carmela; Baroncelli, Silvia; Villani, Paola; Fantoni, Massimo; Tozzi, Valerio; Luca, Andrea De; Cauda, Roberto; Anzidei, Gianfranco; Cusato, Maria; Regazzi, Mario; Floridia, Marco; Tamburrini, Enrica

doi:10.1093/jac/dkq264

Cited by 33 publications

(25 citation statements)

References 4 publications

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“…As shown in other previous reports [4][5][6] our data revealed that raltegravir is effectively transferred across the placenta barrier with an optimal concentration in the neonatal plasma. This effect could be due to the low molecular weight of the drug and its smaller protein-bound (approximately 80% [7]) than protease inhibitors.…”

Section: Dear Sirssupporting

confidence: 88%

“…In conclusion, this and other previous reports [4][5][6] suggest that the standard dose of raltegravir appears to be appropriate during pregnancy, the exposure was not altered during the third trimester and the drug easily crossed the placenta barrier. Even if in this case it cannot be excluded that the newborn low birth weight is unrelated to exposure to raltegravir [5], this case report represents preliminary data on the safety of raltegravir use in pregnancy, which would be a valid option in the management of pregnant women who have been treated with multiple drugs.…”

Section: Dear Sirssupporting

confidence: 79%

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Pharmacokinetic and safety of raltegravir in pregnancy

Croci

Trezzi

Allegri

et al. 2012

Eur J Clin Pharmacol

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Dear Sirs:The aim of anti-HIV treatment in pregnancy is the suppression of the HIV-1 RNA viral load in the plasma before delivery [1] to prevent mother-to-child transmission of the infection. The achievement of this outcome may be complicated in pregnant women who have been treated with multiple drugs by the lack of active drugs available. Although there are limited data on the use of the integrase inhibitor raltegravir in pregnancy, the availability of this drug is important in the management of multidrug-resistant virus in pregnant women.We describe a case of a 22-year-old woman who acquired the infection via vertical transmission and who has been followed up at our Centre since March 2009. Past antiretroviral treatments include numerous drugs; the historical genotypic resistance test showed mutations in the regions of reverse transcriptase (41L, 74V, 101Q, 103N, 103S, 108I, 115F, 179I, 184V, 215D, 215N, 215S, 215Y) and protease (36I, 63P). These mutations confer resistance or poor efficacy to all the nucleoside/nucleotide reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors except etravirine.Since April 2009 the patient has received treatment with tenofovir/emtricitabine (fixed dose combination) plus darunavir/ritonavir (600/100 mg twice daily) plus raltegravir (400 mg twice daily). At the time of conception she presented HIV-RNA <20 cp/mL. Despite safety and pharmacokinetics data of raltegravir in pregnancy being insufficient to recommend its use during pregnancy, it was decided to continue the treatment with tenofovir/emtricitabine (fixed dose combination) plus raltegravir (400 mg twice daily); only darunavir/ ritonavir had been discontinued since the 4th week of pregnancy and substituted with lopinavir/ritonavir (400/100 mg twice daily), the gold standard for protease inhibitors in pregnant women [2]. Therapeutic drug monitoring was performed by a validated HPLC-UV method [3] in the third trimester, which demonstrated good adherence; at that time lopinavir, ritonavir and raltegravir plasma levels were 9.59 μg/mL (minimum target trough concentration 1 μg/mL) [3], 0.81 μg/mL and 0.21 μg/mL (median trough concentration from clinical trials 0.029-0.118 μg/mL) [2].At 39 weeks' gestation a 2.4-kg neonate was delivered by elective caesarean section without complications; at the time of delivery the HIV-RNA viral load in plasma was <20 cp/mL. Despite the low birth weight the infant was healthy; the Apgar scores were 9 and 10 at 1 and 5 min respectively. The mother received zidovudine intravenous prophylaxis during labour and the newborn received 4 weeks of oral zidovudine; the HIV-RNA was undetectable at birth and at 1 and 3 months of age. At delivery the raltegravir level in cord and in maternal plasma was the same (0.19 μg/mL) with a cord/maternal plasma ratio of 1. The lopinavir levels were 1.3 μg/mL and 8.05 μg/mL and the ritonavir levels were 0.26 μg/mL and 0.94 μg/mL, corresponding to a ratio of 0.16 and 0.28 respectively.The low plasma cord concentration of lopinavir can be ex...

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Section: Dear Sirssupporting

confidence: 88%

Section: Dear Sirssupporting

confidence: 79%

Pharmacokinetic and safety of raltegravir in pregnancy

Croci

Trezzi

Allegri

et al. 2012

Eur J Clin Pharmacol

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“…13 In 2010, Pinnetti et al found that adding RGV plus tenofovir to a regimen containing ZDV + lamivudine + darunavir/r resulted in a 2.4 log viral load decline in maternal VL in only 9 days. 20 The mean viral load decline of 2.6 log observed after approximately 17 days of RGV use in our report is consistent with these results. In another small case series, Westling et al showed that adding RGV to four late-presenting, HIV-1-infected pregnant women induced a rapid decay of plasma VL, with no adverse event, and no MTCT.…”

supporting

confidence: 91%

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

Nóbrega¹,

Travassos²,

Haguihara³

et al. 2013

AIDS Research and Human Retroviruses

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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.

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“…Their study was conducted in the Lake Zone area of Northern Tanzania where Schistosoma haematobium and Schistosoma mansoni are endemic [2][3][4]. There is evidence in both animal studies and human studies that show association between schistosomiasis infection and renal diseases ranging from cystitis to immune-mediated glomerulonephropathy [5][6][7][8][9]. There is also evidence showing high prevalence of HIV and schistosomiasis coinfection in their study area [10][11][12].…”

mentioning

confidence: 99%

“…Investigators found that the prevalence of renal disease -particularly albuminuria -is higher in regions in which S. haematobium infection is endemic [6]. Importantly, similar data from adults are lacking.…”

mentioning

confidence: 99%

Renal dysfunction among HIV-infected patients starting antiretroviral therapy in Mwanza, Tanzania

Mpondo

2015

Aids

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Rapid HIV-RNA decline following addition of raltegravir and tenofovir to ongoing highly active antiretroviral therapy in a woman presenting with high-level HIV viraemia at week 38 of pregnancy

Cited by 33 publications

References 4 publications

Pharmacokinetic and safety of raltegravir in pregnancy

Pharmacokinetic and safety of raltegravir in pregnancy

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

Renal dysfunction among HIV-infected patients starting antiretroviral therapy in Mwanza, Tanzania

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