番茄社区

The combination of contraceptive implants and new antiretroviral combination therapy being rolled out in Africa do not appear to have drug-drug interactions with treatment for HIV infection, researchers reported here.

In a pharmacokinetic study, women of child-bearing potential who were using a contraceptive implant had slightly higher levels of etonogestrel when they took dolutegravir-containing antiretroviral therapy relative to HIV-negative women using the implant, reported Rena Patel, MD, MPH, of the University of Washington in Seattle.

"At all time points, the plasma levels of etonogestrel are higher in the dolutegravir patients than in the HIV-negative group curve," she illustrated in a presentation at the virtual Conference on Retroviruses and Opportunistic Infections.

"Higher etonogestrel concentrations in the dolutegravir group are of no safety concerns" she said. "These are the most reassuring data to date."

Patel and colleagues performed the study because more women opt for the long-term etonogestrel implants in Africa as a birth control method. Patel said an estimated 18% of married women in Kenya now use them.

"Concomitant use of efavirenz-containing antiretroviral therapy is known to reduce etonogestrel concentrations, leading to reduced contraceptive effectiveness of subdermal implants," she said. "Dolutegravir-containing antiretroviral therapy is now the preferred first-line regimen for women of reproductive potential. However, dolutegravir's drug-drug interactions with hormonal contraceptives have been narrowly evaluated thus far, and understanding any potential for interactions between subdermal implants and dolutegravir is important as countries pursue national roll-out of dolutegravir-containing antiretroviral therapy."

Before the current study called PARVI was performed, the only other study looking at dolutegravir and hormonal birth control was a 16-woman crossover trial with oral contraceptives. That study showed no differences in pharmacokinetics with or without dolutegravir on board.

Patel said the implants are placed under the skin and are expected to last 3 or 5 years. They begin to work immediately, but their effects can be reversed by removing the implant, she said. She noted that the implants usually yield lower blood progestin concentrations compared with other contraception methods including vaginal rings.

Her group enrolled 195 women in Kisumu, Kenya, from April 2017 to November 2019. Participants were ages 18 to 45 who had initiated birth control with subdermal 68-mg implants in the previous 2 weeks and who planned to use the implant for at least the next 6 months. The 146 HIV-positive women were required to have been on the antiretroviral therapy for at least 30 days and to have achieved viral suppression. Fifty of the HIV-positive women were on efavirenz therapy, and about half were using levonorgestrel implants, but those analyses are still being reviewed, Patel said.

Blood samples were taken at baseline and at weeks 2, 4, 8, 12, 20, 21, 22, 23 and 24. At baseline and at week 4, 8, 12, 16 and 24, hair samples were also collected to check on antiretroviral drug concentrations.

Median age of participants on dolutegravir was 35, versus 25 among the HIV-negative women. The women on dolutegravir had been on their antiretroviral regimens for a median of 6.7 months. The HIV-positive women had a median of 4 children; the HIV-negative women had a median of 3 children.

The only significant difference in adverse events was headaches. About 10% of women on dolutegravir complained of headache compared with 49% of HIV-negative women (P<0.05).

Co-moderator of the oral presentations, Elaine Abrams, MD, of Columbia University in New York City, told 番茄社区, "The study demonstrated that you don't see any important changes in drug levels of either drug when used together. Since the drug levels are unchanged we would not anticipate any change in efficacy."