Pharmacokinetic Interactions Between DMPA and LPV/r Among HIV-Infected Women

The primary study objective was addressed by calculating the Area Under the
Concentration-Time Curve (AUC) from week 0 (prior to DMPA injection) to week 12 (twelve
weeks after DMPA injection) in our study participants.

DMPA was supplied and administered as part of the protocol, however Kaletra was not. It was
required that participants already be on a Kaletra based regimen prior to entering the
study, as described in the eligibility criteria.

Arm A of AIDS Clinical Trial Group (ACTG) A5093, which consisted of 14 participants who were
administered DMPA without Kaletra, was used as reference data.

Inclusion Criteria:

- HIV-1 infection

- Documentation of plasma HIV-1 RNA entry.

- Last menstrual period
- If last menstrual period >35 days prior to study entry, serum follicle-stimulating
hormone (FSH) must be
- Stable anti-retroviral (ARV) regimen consisting of BID LPV/r plus 2 or more
nucleoside reverse transcriptase inhibitors (NRTIs) for at least 30 days if
postpartum or for at least the previous 14 days if on a previously stable
antiretroviral regimen without modifications prior to study entry

- Cluster of Differentiation 4 (CD4+) cell count ≥200 cells/mm^3 within 30 days prior
to study entry

- Certain laboratory values within 30 days prior to study entry

- Premenopausal females with normal ovarian function

- Negative serum or urine-Human Chorionic Gonadotropin (HCG) pregnancy test within 72
hours prior to study entry

- All subjects must agree not to participate in a conception process (e.g., active
attempt to become pregnant or in vitro fertilization) for the duration of the
study.Subjects of reproductive potential, who are participating in sexual activity
that could lead to pregnancy, must agree to use an additional reliable method of
contraception while in the study.

- Ability and willingness to give written informed consent

- Documentation of Pap smear within one year prior to study entry.

- Documentation of hepatitis B (surface antigen) and hepatitis B (core antibody) and
hepatitis C (antibody) status prior to study entry.

- Documentation of varicella-zoster virus (VZV) status by history of varicella or
herpes zoster, or history of varicella or herpes zoster vaccination or documentation
of anti-VZV antibodies.

- Willingness to abstain from alcohol 24 hours prior to and during the 10-hour
pharmacokinetic (PK) specimen draws.

- Willingness to abstain from any grapefruit product or supplement for 24 hours prior
to entry and for the duration of the study.

Exclusion Criteria:

- Received DMPA within 180 days prior to study entry.

- Received other hormonal therapies within the 30 days prior to study entry.

- Concurrent dual nucleoside therapy of zidovudine (ZDV) and stavudine (d4T) within 30
days prior to study entry.

- Use of any prohibited medications within 30 days prior to study entry. Prohibited
Medications were:

- amiodarone (Cordarone)

- astemizole (Hismanal)

- bepridil (Vascor)

- carbamazepine (Tegretol)

- cisapride (Propulsid)

- clarithromycin (Biaxin)

- cyclosporine (Sandimmune, Neoral)

- dihydroergotamine (Migranal and others)

- ergotamine (Ergostat, Gotamine, and others)

- erythromycin (E-mycin, erythromycin ethylsuccinate (EES) and others)

- flecainide (Tambocor)

- glucocorticoids

- Hypericum perforatum (St. John's wort)

- itraconazole (Sporanox)

- ketoconazole (Nizoral)

- lovastatin (Mevacor)

- midazolam (Versed)

- nefazadone (Serzone)

- phenobarbital (Luminal)

- phenytoin (Dilantin)

- pimozide (Orap)

- pioglitazone (Actos)

- propafenone (Rythmol)

- propofol (Diprivan)

- quinidine (Quinidex)

- rifabutin (Mycobutin)

- rifampin (Rifadin, Rifamate, Rifater, Rimactane)

- rosiglitazone (Avandia)

- simvastatin (Zocor)

- tacrolimus (Prograf)

- terfenadine

- ticlopidine (Ticlid), and

- triazolam (Halcion)

- Breastfeeding.

- Less than 30 days postpartum at study entry.

- Bilateral oophorectomy.

- Hypersensitivity to DMPA, MPA, or any of the other ingredients in DMPA.

- More than a 50% change in tobacco smoking within the 30 days prior to study entry or
plans to significantly change tobacco use during the study.

- Invasive cancer of the reproductive tract; known or suspected malignancy of the
breast, or known increased risk for breast cancer; undiagnosed vaginal bleeding;
liver tumors; or serious ocular disorders at any time prior to study entry.

- Uncontrolled hypothyroidism or hyperthyroidism within 30 days of study entry.

- Acute infections or other opportunistic diseases requiring medication within 14 days
prior to study entry.

- Receipt of any immunizations within 2 weeks prior to enrollment.

- Use of any immunosuppressant medication including systemic corticosteroids within 30
days prior to study entry.

- Chronic immunosuppressive conditions other than HIV.

- Initiated, discontinued, or changed doses of drugs that are cytochrome P450 3A4
(CYP3A4) substrates within 30 days of study entry.

- History of deep venous thrombosis or pulmonary emboli.