Depot Contraception With and Without Lopinavir/Ritonavir
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01231451|
Recruitment Status : Withdrawn (Ethics board said the study could not be fully justified.)
First Posted : November 1, 2010
Last Update Posted : November 29, 2010
DMPA (depot medroxyprogesterone acetate or the 'depot' injection) is a widely used contraception. It is popular in woman with HIV as it probably still works when you take HIV drugs. HIV drugs can increase or decrease the level of other drugs (e.g. contraceptives) in your bloodstream which may make them work less well or increase side effects. It is assumed that DMPA can be given with HIV drugs there are no studies proving this.
The purpose of the study is to investigate whether an HIV drug combination containing lopinavir/ritonavir affects DMPA when they are taken at the same time.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection||Drug: DMPA||Phase 1|
Lopinavir/ritonavir (LPV/r) is licensed for use in combination with other antiretrovirals for the treatment of HIV infection. Like other agents from the protease inhibitor class, LPV/r inhibits the 3A isoenzyme of the hepatic cytochrome P450 system and may increase the levels of drugs metabolised via this route. However, LPV/r has also been shown in vivo to induce its own metabolism and to increase the biotransformation of some drugs metabolized by P450 enzymes and by glucuronidation.
Women account for an increasing proportion of the HIV epidemic in the UK. The huge reductions in HIV-related mortality and morbidity associated with the use of effective combination antiretroviral therapy have led to a shift in focus to longer term issues, including reproductive health and contraception. The impact of a variety of antiretrovirals on the plasma pharmacokinetics of oral oestrogen and progesterone preparations have been investigated and in general NNRTIs and boosted PIs cause a reduction in levels of both, particularly oral oestrogen preparations. Most package inserts for combined (oestrogen and progestogen) and progestogen-only oral contraceptives recommend that additional contraceptive methods be employed with concomitant use of enzyme-inducing agents.
Injectable contraception provides highly effective contraception without the need for daily pill taking, an important factor to consider for individuals already taking regular medication. Depot medroxyprogesterone acetate (DMPA) is the most frequently prescribed injectable method. DMPA, like other progestogens, is metabolised by the cytochrome P450 system but interaction studies in women on antiretrovirals are limited. A study of 59 women on DMPA contraception plus an unboosted PI (nelfinavir) or an NNRTI (efavirenz or nevirapine) measured DMPA levels and compared them with 16 women on either no therapy or NRTIs only (no potential for drug interaction). DMPA levels were similar in all groups and suppression of ovulation over a 12 week period was also similar in all groups.
Although the high levels of DMPA achieved over the dosing interval make any pharmacokinetic interaction unlikely to be clinically significant, some clinicians advise a reduction in the interval between DMPA injections from 12 to 10 weeks in patients on an NNRTI or boosted PI; there is no clear evidence to support this approach. Although the described study supports normal dosing intervals for women on an NNRTI, the unboosted PI nelfinavir is not recommended as standard of care and the impact of ritonavir-boosted PIs is unclear. The summary of product characteristics for DMPA advises a normal dosing interval even when using a potent enzyme inducers, suggesting no additional intervention is required when prescribing a boosted PI. Formal pharmacokinetic data is crucial to clarify this important area.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Pharmacokinetics of Depot Medroxyprogesterone Acetate (DMPA) in the Absence and Presence of Lopinavir/Ritonavir in HIV-1 Infected Women|
|Study Start Date :||December 2010|
|Estimated Primary Completion Date :||June 2011|
|Estimated Study Completion Date :||June 2011|
Experimental: All Subjects
All Subjects will receive the same intervention
All subjects will take DMPA
- pharmacokinetics of depot medroxyprogesterone acetate (DMPA) [ Time Frame: week 1 - week 24 ]
To investigate the pharmacokinetics of depot medroxyprogesterone acetate (DMPA) in the absence and presence of lopinavir/ritonavir in HIV-
1 infected women
- Impact of co-administration of DMPA and lopinavir/ritonavir [ Time Frame: Week 1 - week 24 ]To investigate the impact of co-administration of DMPA and lopinavir/ritonavir on surrogate markers of contraceptive efficacy (LH, FSH, oestradiol)
- Safety of DMPA [ Time Frame: Week 1 - week 24 ]To investigate the safety of DMPA in HIV infected women on lopinavir/ritonavir
- Impact of DMPA on lopinavir/ritonavir plasma concentrations [ Time Frame: week 1 - week 24 ]To investigate the impact of DMPA on lopinavir/ritonavir plasma concentrations compared with historical controls
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01231451
|St Stephen's Centre|
|London, United Kingdom, SW10 9NH|