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Intrauterine Insemination In HIV-Discordant Couples (ARTEMIS)

Primary Purpose

HIV-1, Fertility, Infertility

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Sperm Washing with Intrauterine Insemination (IUI)

About this trial

This is an interventional treatment trial for HIV-1 focused on measuring Acquired Immune Deficiency Syndrome, Assisted Reproductive Technology, Fertility, HIV, HIV Discordant, Infertility, Intrauterine Insemination, Sexually Transmitted Diseases, Sperm Washing

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Couples with HIV discordance with an HIV seronegative female partner and HIV seropositive male partner
Men must be HIV positive with an undetectable viral load (<75 copies/ml)
Men must be clinical stable on antiretroviral therapy for 6 months
Men must have a CD4 count > 250 at screening
Men must be between 18-50 years of age
Men must have a baseline test sperm preparation demonstrating at least 10 million motile sperm per sample
Men must have a letter of medical clearance specific for this procedure from primary care physician stating that subject is in good health and psychologically stable
Men must be willing to have constituent follow-up of HIV care throughout study participation
Women must have an HIV-1/HIV-2 negative serology at screening
Women must be between 18-40 years of age
Women must have a body mass index (BMI) less than 30
Women must be a non-smoker
Women must be ovulatory (as determined by LH tracking)
Women must have normal uterine cavity with at least one documented patent fallopian tube (as determined by hysterosalpingogram)
Women must have adequate day 3 ovarian reserves: FSH,12 mlU/ml and estradiol<80pg/ml
Women must have no evidence of active urogenital infection at screening
Women must have a normal PAP smear and GC/Chlamydia at screening
Women must have a letter of medical clearance specific to this procedure from subject's primary care physician stating that subject is in good health and psychological stable.

Exclusion Criteria:

Subjects with untreated sexually transmitted diseases (syphilis, GC, CT)
Men with detectable viral load (>75) at screening
Subjects with any condition (including, but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the subject's safety or adherence to the protocol
Subjects with any uncontrollable medical or psychiatric condition that,in the opinion of the investigator, cannot be adequately stabilized and could be considered a contraindication to participation

Sites / Locations

Boston Medical Center

Outcomes

Primary Outcome Measures

Pregnancy

A serum pregnancy test will be performed 16 days after IUI if menses is missed.

Secondary Outcome Measures

Post-IUI HIV Infection of Female Subject

The female subject will be tested for HIV by branch-DNA (b-DNA) test four weeks after each insemination.

Female Subject HIV-1/HIV-2 Serology

If the female subject does not become pregnant, she will be tested for HIV-1/HIV-2 serology at 3 months, 6 months and 12 months after the insemination. If repeat inseminations are performed, the above-stated timeline will be followed based on the last insemination performed. If the female subject does become pregnant, she will be tested for HIV-1/HIV-2 serology at 3 months, 6 months and 9 months after the insemination, and again at 3 months postpartum.

Infant HIV-1/HIV-2 Serology

For a successful birth, the infant will undergo an HIV-1/HIV-2 serology test at three months of age.

Full Information

NCT ID

NCT01173276

First Posted

July 28, 2010

Last Updated

February 19, 2016

Sponsor

Boston Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01173276

Brief Title

Intrauterine Insemination In HIV-Discordant Couples

Acronym

ARTEMIS

Official Title

Intrauterine Insemination In HIV-Discordant Couples

Study Type

Interventional

2. Study Status

Record Verification Date

January 2012

Overall Recruitment Status

Terminated

Why Stopped

The field has changed, and we have decided to develop a PrEP program.

Study Start Date

September 2009 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boston Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Detailed Description

This study aims to assess the feasibility of a novel standard of care technique for intrauterine insemination (IUI) in HIV-discordant couples in the United States. This study will involve couples in which the male partner is HIV positive, but the female partner is negative. The investigators will institute a protocol similar to those used presently throughout Europe with good success. To date, no HIV seroconversions have occurred in over 4000 inseminations performed in HIV serodiscordant couples. All male subjects will be on stable HAART and have undetectable serum viral loads prior to insemination. For semen samples, seminal fluid will be separated from sperm using a density gradient/swim-up separation technique. The purified sperm sample will be washed, and screened for HIV RNA using sensitive real-time RT-PCR. Samples with detectable traces of HIV RNA will not be used for insemination. Samples with no detectable traces of HIV RNA will be used for a standard intrauterine insemination of the female partner. Female subjects will be followed post-insemination for seroconversion and pregnancy. Infants will be followed for seroconversion at birth through 3 months of age. The data being collected in this pilot feasibility study will be mostly descriptive, lacking sample size to achieve statistical power for testing. However, the investigators will use case-control analysis to compare couples who achieve pregnancy with those who do not across demographics and markers of HIV disease progression. Additionally, the investigators have developed a 14 item, 5-point Likert scale to assesses the psychosocial impact of reproductive health issues stemming from HIV-discordance in both the female and male participants. The expected duration for any unique subject couple is 3 to 12 months, depending on pregnancy. It is expected that the interventional portion of this study will continue for up to 2 years, depending on pregnancies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV-1, Fertility, Infertility

Keywords

Acquired Immune Deficiency Syndrome, Assisted Reproductive Technology, Fertility, HIV, HIV Discordant, Infertility, Intrauterine Insemination, Sexually Transmitted Diseases, Sperm Washing

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Other

Intervention Name(s)

Sperm Washing with Intrauterine Insemination (IUI)

Intervention Description

For semen samples, seminal fluid will be separated from sperm using a density gradient/swim-up separation technique. The purified sperm sample will be washed, and screened for HIV RNA using sensitive real-time RT-PCR. Samples with detectable traces of HIV RNA will not be used for insemination. Samples with no detectable traces of HIV RNA will be used for a standard intrauterine insemination of the female partner.

Primary Outcome Measure Information:

Title

Pregnancy

Description

A serum pregnancy test will be performed 16 days after IUI if menses is missed.

Time Frame

Sixteen days after IUI

Secondary Outcome Measure Information:

Title

Post-IUI HIV Infection of Female Subject

Description

The female subject will be tested for HIV by branch-DNA (b-DNA) test four weeks after each insemination.

Time Frame

Four weeks after IUI

Title

Female Subject HIV-1/HIV-2 Serology

Description

Time Frame

Three, six, nine (pregnant only) and twelve months after insemination

Title

Infant HIV-1/HIV-2 Serology

Description

For a successful birth, the infant will undergo an HIV-1/HIV-2 serology test at three months of age.

Time Frame

Three months of age

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Couples with HIV discordance with an HIV seronegative female partner and HIV seropositive male partner Men must be HIV positive with an undetectable viral load (<75 copies/ml) Men must be clinical stable on antiretroviral therapy for 6 months Men must have a CD4 count > 250 at screening Men must be between 18-50 years of age Men must have a baseline test sperm preparation demonstrating at least 10 million motile sperm per sample Men must have a letter of medical clearance specific for this procedure from primary care physician stating that subject is in good health and psychologically stable Men must be willing to have constituent follow-up of HIV care throughout study participation Women must have an HIV-1/HIV-2 negative serology at screening Women must be between 18-40 years of age Women must have a body mass index (BMI) less than 30 Women must be a non-smoker Women must be ovulatory (as determined by LH tracking) Women must have normal uterine cavity with at least one documented patent fallopian tube (as determined by hysterosalpingogram) Women must have adequate day 3 ovarian reserves: FSH,12 mlU/ml and estradiol<80pg/ml Women must have no evidence of active urogenital infection at screening Women must have a normal PAP smear and GC/Chlamydia at screening Women must have a letter of medical clearance specific to this procedure from subject's primary care physician stating that subject is in good health and psychological stable. Exclusion Criteria: Subjects with untreated sexually transmitted diseases (syphilis, GC, CT) Men with detectable viral load (>75) at screening Subjects with any condition (including, but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the subject's safety or adherence to the protocol Subjects with any uncontrollable medical or psychiatric condition that,in the opinion of the investigator, cannot be adequately stabilized and could be considered a contraindication to participation

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Margaret M Sullivan, MD

Organizational Affiliation

Boston Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Boston Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

12859847

Citation

Anderson DJ, Politch JA. Providing fertility care to HIV-1 serodiscordant couples: a biologist's point of view. Am J Bioeth. 2003 Winter;3(1):47-9. doi: 10.1162/152651603321611980. No abstract available.

Results Reference

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PubMed Identifier

17721098

Citation

Bujan L, Hollander L, Coudert M, Gilling-Smith C, Vucetich A, Guibert J, Vernazza P, Ohl J, Weigel M, Englert Y, Semprini AE; CREAThE network. Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: results from the European CREAThE network. AIDS. 2007 Sep 12;21(14):1909-14. doi: 10.1097/QAD.0b013e3282703879.

Results Reference

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PubMed Identifier

15482760

Citation

Bujan L, Pasquier C, Labeyrie E, Lanusse-Crousse P, Morucci M, Daudin M. Insemination with isolated and virologically tested spermatozoa is a safe way for human immunodeficiency type 1 virus-serodiscordant couples with an infected male partner to have a child. Fertil Steril. 2004 Oct;82(4):857-62. doi: 10.1016/j.fertnstert.2004.02.128.

Results Reference

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PubMed Identifier

3122014

Citation

Centers for Disease Control (CDC). Semen banking, organ and tissue transplantation, and HIV antibody testing. MMWR Morb Mortal Wkly Rep. 1988 Feb 5;37(4):57-8, 63. No abstract available.

Results Reference

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PubMed Identifier

2109169

Citation

Centers for Disease Control (CDC). HIV-1 infection and artificial insemination with processed semen. MMWR Morb Mortal Wkly Rep. 1990 Apr 20;39(15):249, 255-6. No abstract available.

Results Reference

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PubMed Identifier

11718472

Citation

Centers for Disease Control and Prevention. Revised guidelines for HIV counseling, testing, and referral. MMWR Recomm Rep. 2001 Nov 9;50(RR-19):1-57; quiz CE1-19a1-CE6-19a1.

Results Reference

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PubMed Identifier

11425804

Citation

Englert Y, Van Vooren JP, Place I, Liesnard C, Laruelle C, Delbaere A. ART in HIV-infected couples: has the time come for a change of attitude? Hum Reprod. 2001 Jul;16(7):1309-15. doi: 10.1093/humrep/16.7.1309.

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PubMed Identifier

11821074

Citation

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PubMed Identifier

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Citation

Gilling-Smith C, Nicopoullos JD, Semprini AE, Frodsham LC. HIV and reproductive care--a review of current practice. BJOG. 2006 Aug;113(8):869-78. doi: 10.1111/j.1471-0528.2006.00960.x. Epub 2006 Jun 2.

Results Reference

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PubMed Identifier

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Citation

Gilling-Smith C, Smith JR, Semprini AE. HIV and infertility: time to treat. There's no justification for denying treatment to parents who are HIV positive. BMJ. 2001 Mar 10;322(7286):566-7. doi: 10.1136/bmj.322.7286.566. No abstract available.

Results Reference

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PubMed Identifier

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Citation

Marina S, Marina F, Alcolea R, Exposito R, Huguet J, Nadal J, Verges A. Human immunodeficiency virus type 1--serodiscordant couples can bear healthy children after undergoing intrauterine insemination. Fertil Steril. 1998 Jul;70(1):35-9. doi: 10.1016/s0015-0282(98)00102-2.

Results Reference

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PubMed Identifier

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Citation

Pasquier C, Anderson D, Andreutti-Zaugg C, Baume-Berkenbosch R, Damond F, Devaux A, Englert Y, Galimand J, Gilling-Smith C, Guist'hau O, Hollander L, Leruez-Ville M, Lesage B, Maillard A, Marcelin AG, Schmitt MP, Semprini A, Vourliotis M, Xu C, Bujan L; CREAThE Network. Multicenter quality control of the detection of HIV-1 genome in semen before medically assisted procreation. J Med Virol. 2006 Jul;78(7):877-82. doi: 10.1002/jmv.20636.

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Citation

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Citation

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Citation

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Citation

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Results Reference

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Intrauterine Insemination In HIV-Discordant Couples

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