Intrauterine Insemination In HIV-Discordant Couples

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.

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