In the Journals

Isentress effectively prevents vertical transmission of HIV

The use of Isentress in HIV-infected pregnant women was well tolerated and effective in preventing mother-to-child HIV transmission, according to recent findings.

“In current U.S. and European treatment guidelines for HIV-1 infection in pregnancy, preferred combined antiretroviral agents include two nucleoside/nucleotide reverse transcriptase inhibitors in combination with the protease inhibitors lopinavir or atazanavir boosted with ritonavir or the non-nucleoside reverse transcriptase inhibitor nevirapine,” researchers wrote in Clinical Infectious Diseases. “Regimens including the HIV-1 integrase inhibitor [Isentress (raltegravir, Merck)] can be considered for use in special circumstances because information on the pharmacokinetics and the safety of raltegravir in pregnancy is limited.”

In an open-label, multicenter phase 4 study, researchers enrolled 22 HIV-infected pregnant women at 10 European hospitals who underwent treatment with 400 mg raltegravir twice daily. Fifteen patients initiated raltegravir during pregnancy. The study’s efficacy outcomes were undetectable HIV RNA load (< 50 copies/mL), assessed before or at delivery, and HIV infection status of the infant as determined by PCR. The researchers evaluated pharmacokinetic activity of raltegravir at roughly week 33 and around 4 to 6 weeks postpartum. They measured levels of raltegravir in plasma utilizing validated reversed phase high-pressure liquid chromatography.

The researchers found that as delivery neared, 86% of the patients had undetectable viral load, and none of the children was born with HIV. Raltegravir exposure was found to be highly variable, however. Overall, the mean area under the curve (AUC) plasma levels in the third trimester were 29% lower than the postpartum levels, and the third-trimester C12H plasma concentrations of raltegravir were 36% lower than the postpartum levels. The geometric mean ratio for AUC0-12h was 0.71 (90% CI, 0.54-0.96), and the geometric mean ratio for C12H was 0.64 (90% CI, 0.34-1.22). The median interquartile range ratio of raltegravir cord/maternal blood in nine patients was 1.21 (90% CI, 1.02-2.17).

According to the researchers, these findings support the utility of raltegravir as a means of preventing mother-to-child HIV transmission.

“Raltegravir in combination with other antiretroviral agents was effective in preventing mother-to-child transmission by reducing and/or maintaining HIV RNA viral load at an undetectable or low level,” the researchers wrote. “Our data support the use of raltegravir in standard dosages in HIV-infected pregnant women for the prevention of mother-to-child transmission.”

Disclosure: Blonk reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.

The use of Isentress in HIV-infected pregnant women was well tolerated and effective in preventing mother-to-child HIV transmission, according to recent findings.

“In current U.S. and European treatment guidelines for HIV-1 infection in pregnancy, preferred combined antiretroviral agents include two nucleoside/nucleotide reverse transcriptase inhibitors in combination with the protease inhibitors lopinavir or atazanavir boosted with ritonavir or the non-nucleoside reverse transcriptase inhibitor nevirapine,” researchers wrote in Clinical Infectious Diseases. “Regimens including the HIV-1 integrase inhibitor [Isentress (raltegravir, Merck)] can be considered for use in special circumstances because information on the pharmacokinetics and the safety of raltegravir in pregnancy is limited.”

In an open-label, multicenter phase 4 study, researchers enrolled 22 HIV-infected pregnant women at 10 European hospitals who underwent treatment with 400 mg raltegravir twice daily. Fifteen patients initiated raltegravir during pregnancy. The study’s efficacy outcomes were undetectable HIV RNA load (< 50 copies/mL), assessed before or at delivery, and HIV infection status of the infant as determined by PCR. The researchers evaluated pharmacokinetic activity of raltegravir at roughly week 33 and around 4 to 6 weeks postpartum. They measured levels of raltegravir in plasma utilizing validated reversed phase high-pressure liquid chromatography.

The researchers found that as delivery neared, 86% of the patients had undetectable viral load, and none of the children was born with HIV. Raltegravir exposure was found to be highly variable, however. Overall, the mean area under the curve (AUC) plasma levels in the third trimester were 29% lower than the postpartum levels, and the third-trimester C12H plasma concentrations of raltegravir were 36% lower than the postpartum levels. The geometric mean ratio for AUC0-12h was 0.71 (90% CI, 0.54-0.96), and the geometric mean ratio for C12H was 0.64 (90% CI, 0.34-1.22). The median interquartile range ratio of raltegravir cord/maternal blood in nine patients was 1.21 (90% CI, 1.02-2.17).

According to the researchers, these findings support the utility of raltegravir as a means of preventing mother-to-child HIV transmission.

“Raltegravir in combination with other antiretroviral agents was effective in preventing mother-to-child transmission by reducing and/or maintaining HIV RNA viral load at an undetectable or low level,” the researchers wrote. “Our data support the use of raltegravir in standard dosages in HIV-infected pregnant women for the prevention of mother-to-child transmission.”

Disclosure: Blonk reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.