CROI: Saquinavir-based combination prevents mother-to-child HIV transmission

Short-term anti-HIV drug combinations including ritonavir (Norvir)-boosted saquinavir (Invirase) are more effective at reducing viral loads in the third trimester of pregnancy than nelfinavir (Viracept)-based combinations, according to an Irish study presented earlier this month at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver.

This may make saquinavir-based treatment a viable option for the prevention of HIV transmission to babies during childbirth.

The levels of protease inhibitors in the blood are often low in pregnant women. These low levels can put the mothers at risk of drug resistance and treatment failure, as well as an increased risk of HIV transmission rates when used to prevent mother-to-child HIV transmission.

To assess the usefulness of drug combinations including ritonavir-boosted saquinavir, investigators from Dublin treated 17 HIV-positive women with these drugs plus a combination of 3TC and AZT as Combivir for at least six weeks, starting in the third trimester of pregnancy. The women received the standard dose of two 500mg tablets of saquinavir plus 100mg ritonavir and one Combivir tablet twice a day.

At week 36 of pregnancy, 14 (88%) of the women had viral loads below 50 copies/ml, while two (12%) had viral loads between 50 and 1000 copies/ml. One woman switched from ritonavir-boosted saquinavir to nelfinavir after ten days due to severe vomiting.

The investigators compared these findings to a cohort of 47 women treated with 1250mg nelfinavir and Combivir twice a day for the same period.

Only 27 (56%) of these women had viral loads below 50 copies/ml at week 36, while 18 (38%) had viral loads between 50 and 1000 copies/ml and three (6%) had viral loads above 1000 copies/ml. These values were significantly different from the saquinavir-treated group (p

There was one HIV transmission during the study. This occurred in the nelfinavir group in a woman whose viral load was below 50 copies/ml, but whose waters broke more than 24 hours before delivery. This is a known risk factor for HIV transmission during childbirth.

Problems with treatment adherence were found in six of the nelfinavir-treated women, although four of these had viral loads below 50 copies/ml. No adherence issues were seen in the saquinavir group.

The investigators conclude that the superior outcome in the saquinavir-treated women was due to saquinavir being more likely to produce adequate drug levels in pregnant women. This was supported by the observation that blood levels of saquinavir were over 100ng/ml in six women.

All of the women stopped treatment after they had given birth, after a median of eleven weeks of treatment. No primary protease inhibitor resistance mutations were seen in samples taken from 41 women six weeks after delivery.

The investigators concluded: “The absence of protease inhibitor mutations in either group post-treatment suggests that short-term treatment with either protease inhibitor has no apparent detrimental effect on future antiretroviral therapy options.”