- To determine if doubling the dose of the LNG EC effectively overcomes the known drug-drug interaction (DDI) with EFV-based ART.
- To determine if doubling the dose of the LNG EC effectively overcomes the expected DDI with RIF-containing TB therapy.
- To estimate the difference in LNG pharmacokinetic (PK) exposure with double-dose LNG EC compared to standard-dose LNG EC in women receiving EFV-based ART.
- To estimate the difference in LNG PK exposure with standard-dose LNG EC in women receiving EFV-based ART compared to women receiving DTG-based ART.
- To verify the absence of significant DDI between LNG EC and DTG-based ART.
- To compare the safety of double-dose LNG EC compared to standard-dose LNG EC.
- To evaluate the relationship between baseline measures of body weight (body fat percentage, total weight, and body mass index [BMI]) and LNG PK exposure.
Study Design: A5375 is a phase II, open-label, four parallel group, partially randomized, pharmacokinetic (PK) study to evaluate if a double dose of levonorgestrel (LNG) emergency contraception (EC) overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based antiretroviral therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The safety of double-dose LNG EC versus standard-dose will also be compared.
Participants will be volunteers who do not currently require EC for contraception. Eligible participants will receive a single dose (1.5 mg) or a double dose (3.0 mg) of LNG EC based on their group assignment, which will be determined by their infection (HIV or TB; participants cannot be coinfected), and, for those who are living with HIV, by their ART regimen at enrolment. Women living with HIV who are taking EFV-based ART will be randomized to Group A or B (1:2 ratio). Women taking dolutegravir (DTG)-based ART will be assigned to Group C. Women who are HIV-negative and in the continuation phase of TB treatment taking RIF and isoniazid (INH) will be assigned to Group D.
Study Population: Women who are 18 years of age or older, and who are either HIV+ and on stable ART, or who are HIV- and in the continuation phase of anti-TB therapy on daily INH/RIF.
Study Duration: 4 weeks
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
A total of 122 persons participated in this study. Results from the 66 participants who were receiving rifampicin (RIF)-containing anti-TB therapy or dolutegravir (DTG)-containing ART for participants living with HIV were presented at CROI. The DTG-containing ART group was used as a control group, because it is known that DTG does not interact with LNG and can be used with the standard dose of LNG.
The results showed that the amount of LNG in the body (called LNG levels) were similar over the first 24 hours in participants receiving RIF plus a double-dose of LNG compared to participants on DTG plus a standard-dose LNG. Even though the LNG level were 27% higher in the double dose group compared to the standard dose group, we did not see more severe side effects in participants taking this double dose. These results are important and provide evidence that doubling the dose of LNG is needed when taken with RIF, since RIF speeds up the removal of LNG from the body when they are taken together. These results are in agreement with some clinical guidelines that suggest the need to take a double dose of LNG when it is taken with RIF.