Clinical trial NCT00666055: Sex, Aging and Antiretroviral Pharmacokinetics
Official title: CID 0708 - Sex, Aging and Antiretroviral Pharmacokinetics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Sex
Aging
Antiretroviral
Pharmacokinetics
post-menopausal women with HIV infection
pre-menopausal women with HIV infection
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2008-04-24
Enrollment: 11
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will primarily be recruited from the UNC Infectious Disease Clinic and the Wake County HIV Clinic.

Brief summary: The purpose of this research study is to learn about levels of antiretroviral drug levels and response to HIV virus in the genital tract of women who are post-menopausal. The investigators in this study think that the levels of hormones post-menopausal HIV-infected women may have in their bodies may affect the levels of antiretroviral drug, and therefore affect how much HIV virus they have in their bodies. Since women who have already gone through menopause have different levels of hormones, such as estrogen, than women who are pre-menopausal, the investigators would like to check the levels of antiretroviral drugs in their blood, their genital secretions, and their genital tissue.

Detailed description: Purpose: To longitudinally quantify systemic and genital tract antiretroviral pharmacokinetics and viral responses in HIV-infected post-menopausal women. These parameters will be compared to pre-menopausal women to determine if the absence or presence of estrogen influences treatment responses and infectiousness of HIV.

Participants: 30 post-menopausal and 12 pre-menopausal HIV-infected women Procedures (methods): First dose, steady state, and longitudinal pharmacokinetics of the most commonly prescribed antiretroviral agents will be assessed in the systemic and genital tract compartments in a cohort of post- and pre-menopausal HIV-infected women. Concurrent blood plasma and genital secretions HIV RNA will be measured. Systemic and genital tract virologic responses will be correlated with antiretroviral concentrations and with each other.

Eligibility criteria: Inclusion Criteria:

1. HIV-infected women \>18 years of age
2. There are no specific entry criteria for CD4+ T-cell counts and plasma HIV RNA.
3. Menopause status will be determined at screening.

   1. Post-menopausal will be defined as the cessation of menses for \>12 months (or undergone a bilateral oophorectomy with or without a hysterectomy) AND a FSH \>25 miu/mL and estradiol level \<20 pg/mL establishing both physiological and biochemical evidence of menopause.
   2. Pre-menopausal women must have regular cycles without peri-menopausal vasomotor symptoms and not receiving exogenous hormones.
4. Women may be changing to a new regimen because of virologic failure or intolerability. Women in whom resistance testing is available, two or more drugs to which the virus is susceptible needs to be included in the proposed treatment regimen.
5. Women may also be naïve to either NNRTI or PIs and initiating their first, second or third HAART regimen (ARVs to be investigated: zidovudine, lamivudine, emtricitabine, abacavir, tenofovir, efavirenz, lopinavir/ritonavir, atazanavir with or without ritonavir).
6. Provided the ARV regimens contain one or more of the agents under study they may also include new agents such as maraviroc (CCR5 inhibitor), raltegravir (integrase inhibitor) and/or etravirine (NNRTI). Samples will be stored so that the pharmacokinetics of these agents can be evaluated in future studies once the assays are available in our lab.
7. Women must be free from sexually transmitted infections (STI's) at the time of enrollment.
8. Women must be able to abstain from douching and sexual activity for 72 hours prior to all study visits.
9. Subjects must be willing to have genital tract samples taken.

Exclusion Criteria:

1. Women currently receiving medication with known drug-drug interaction with the ARVs under study.
2. Women currently receiving any exogenous hormone therapy (contraception, estrogen replacement therapy or androgen supplements). Women must be off all exogenous hormone therapy for \> 16 weeks prior to enrollment.
3. Women who are pregnant or breast-feeding.
4. Women with a hemoglobin \<9.0g/dL and/or hematocrit \<28%.
5. Women unable to complete, or have a caretaker complete, a dose administration card.
6. Women who, in the judgement of the investigator, are unable to comply with the protocol requirements.
7. Women who are unable to give written informed consent.
8. Women who cannot comply with abstaining from intercourse or douching 48 hours prior to study examination.
9. Male or transgender individuals.

Primary outcomes:
measure: To measure and compare steady state blood plasma pharmacokinetics of antiretroviral therapies in post- and pre-menopausal HIV-infected women.
timeFrame: 6 months
Secondary outcomes:
measure: To longitudinally quantify and compare genital tract antiretroviral drug exposure in post- and pre-menopausal HIV-infected women
timeFrame: 6 months
measure: To determine and compare sexual HIV infectivity in post- and pre-menopausal HIV-infected women by measuring HIV RNA dynamics in blood plasma and genital tract secretions before and after the initiation of highly active antiretroviral therapy.
timeFrame: 6 months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Kristine B Patterson, MD
role: PRINCIPAL_INVESTIGATOR
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