Sex, Aging and Antiretroviral Pharmacokinetics

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Kristine Patterson, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00666055
First received: April 22, 2008
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention
HIV Infections
Drug: ARV regimen chosen by treating physician

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: CID 0708 - Sex, Aging and Antiretroviral Pharmacokinetics

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • To measure and compare steady state blood plasma pharmacokinetics of antiretroviral therapies in post- and pre-menopausal HIV-infected women. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To longitudinally quantify and compare genital tract antiretroviral drug exposure in post- and pre-menopausal HIV-infected women [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood; genital secretions; genital tissue


Enrollment: 11
Study Start Date: March 2008
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Group 1
30 post-menopausal HIV-infected women
Drug: ARV regimen chosen by treating physician

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).

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).

Other Names:
  • Zidovudine: ZDV, Retrovir, Retrovis, AZT (Azidothymidine)
  • Lamivudine: 3TC, Zeffix, Epivir, Epivir-HBV
  • Emtricitabine: FTC, Emtriva
  • Abacivir: Ziagen
  • Tenofovir: TDF, Viread
  • Efavirenz: Sustiva, Stocrin
  • Lopinavir/Ritonavir: Kaletra, Aluvia
  • Atazanavir: Reyataz
  • Ritonavir: Norvir
  • Maraviroc: Selzentry
  • Raltegravir: MK-0518, Isentress
  • Etravirine: TMC-125, Intelence
Group 2
12 pre-menopausal HIV-infected women
Drug: ARV regimen chosen by treating physician

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).

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).

Other Names:
  • Zidovudine: ZDV, Retrovir, Retrovis, AZT (Azidothymidine)
  • Lamivudine: 3TC, Zeffix, Epivir, Epivir-HBV
  • Emtricitabine: FTC, Emtriva
  • Abacivir: Ziagen
  • Tenofovir: TDF, Viread
  • Efavirenz: Sustiva, Stocrin
  • Lopinavir/Ritonavir: Kaletra, Aluvia
  • Atazanavir: Reyataz
  • Ritonavir: Norvir
  • Maraviroc: Selzentry
  • Raltegravir: MK-0518, Isentress
  • Etravirine: TMC-125, Intelence

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

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects will primarily be recruited from the UNC Infectious Disease Clinic and the Wake County HIV Clinic.

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00666055

Locations
United States, North Carolina
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7215
Sponsors and Collaborators
Kristine Patterson, MD
Investigators
Principal Investigator: Kristine B Patterson, MD University of North Carolina, Chapel Hill
  More Information

Publications:
Gruber CJ, Tschugguel W, Schneeberger C, Huber JC. Production and actions of estrogens. N Engl J Med. Jan 31 2002;346(5):340-352.
Royce RA, Sena A, Cates W, Jr., Cohen MS. Sexual transmission of HIV. N Engl J Med. Apr 10 1997;336(15):1072-1078.
Bebell L, Passmore J, Williamson C, et al. Clincial correlations of inflammatory cytokines in the female genital tract during acute HIV-1 infection. Paper presented at: 16th International AIDS Conference, 2006; Toronto, Canada.
Gleiter CH, Gundert-Remy U. Gender differences in pharmacokinetics. Eur J Drug Metab Pharmacokinet. Apr-Jun 1996;21(2):123-128.
Columbo S, Buclin T, Decosterd L, al. e. Orosmucoid plasma concentrations and genetic variants: effects on protease inhibitor clearance and cellular accumulation ratio. Paper presented at: 7th International Workshop on Clinical Pharmacology of HIV Therapy; April 20-22, 2006, 2006; Lisbon, Portugal.
Gatti G, dePascalis C, deLucca A. Predictors of amprenavir parameters of drug exposure in heavily pretreated HIV positive patients. Paper presented at: Proceedings on the 6th International Congress on Drug therapy in HIV infection, 2002; Glasgow, Scotland.
Umeh O, Currier J, Park J, et al. Sex differences in lopinavir/ritonavir soft gel capsule pharmacokinetics among HIV-infected females and males. Paper presented at: 14th Conference on Retroviruses and Opportunistic Infections, 2007; Los Angelos, CA.
Vernazza PL, Kashuba AD, Cohen MS. Biological Correlates of Sexual Transmission of HIV Practical Consequences and Potential Targets for Public Health. Reviews in Medical Microbiology. July 2001;12(3):131-142.
Dumond J, Yeh R, Patterson K, et al. First Dose and Steady-state Genital Tract Pharmacokinetics of Ten Antiretroviral Drugs in HIV-infected Women: Implications for Pre- and Post- Exposure Prophylaxis. Paper presented at: 13th Conference on Retroviruses and Opportunistic Infections, 2006; Denver, CO.
Reddy S, Troiani L, Pereira A, et al. Zidovudine and Lamivudine (ZDV/3TC) Seminal Plasma:Blood Plasma (SP:BP) Concentration (CONC) Ratios Do Not Predict Total SP Exposure. Paper presented at: World AIDS Conference, 2002; Barcelona, Sapin.
Jung B, Rezk N, Bridges A, Kashuba A. Simultaneous determination of 16 antiretroviral drugs in human plasma for quantitative analysis with liquid chromatography-tandem mass spectrometry. Biomedical Chromatography. 2007;In press.

Responsible Party: Kristine Patterson, MD, Clinical Associate Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00666055     History of Changes
Other Study ID Numbers: CID 0708, 1K23AI077355-01
Study First Received: April 22, 2008
Last Updated: September 18, 2012
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by University of North Carolina, Chapel Hill:
Sex
Aging
Antiretroviral
Pharmacokinetics
post-menopausal women with HIV infection
pre-menopausal women with HIV infection

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Lamivudine
Tenofovir
Efavirenz
Ritonavir
Lopinavir
Atazanavir
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 15, 2014