Pre-Exposure Prophylaxis and Timed Intercourse for HIV-Discordant Couples

Human immunodeficiency virus (HIV) infection has now become a treatable disease and many
infected individuals are interested in having a family. Couples in which the man is infected
but the woman is HIV-negative (hereafter referred to as HIV-discordant) require medical
intervention during procreation to prevent HIV transmission to the female and her child. The
current view is that reducing the number of infections involving unprotected intercourse in
HIV-discordant couples is a public health issue in the U.S.

The risk of HIV transmission by regular intercourse in HIV-discordant couples in a stable
relationship is about 1 case for every 1000 sexual acts. However, the risk is extremely low
if 1) the couple is monogamous; 2) there is no intravenous (IV) drug use; 3) the man has low
HIV viral load, a high CD4 count (CD4 cells are white blood cells that are attacked by HIV),
and no symptoms of the disease; 4) the couple is free of other sexually transmitted
infections; 5) the male and female genital tracts are free of sores; 6) the man is
circumcised; and 7) the man is taking antiretroviral treatment (ART). In fact, studies in
African HIV-discordant couples have found no transmission of HIV if patients either have low
blood levels of HIV, no symptoms of HIV infection or are taking ART.

The safest methods for HIV-discordant couples are insemination using a sperm donor, adoption
and remaining childless. However, some couples strongly desire a biologically related child.
Fertility clinics in the U.S. have been resistant to treating HIV-discordant couples.
Generally, the available treatment in the U.S. involves in vitro fertilization (IVF), which
involves collecting sperm and eggs from the couple and allowing fertilization to occur in the
laboratory, with intracytoplasmic sperm injection (ICSI), in which a single sperm is injected
directly into the egg. One cycle of treatment costs more than 20% of the median annual income
in the U.S., and the birth rate with this method is approximately 35% per cycle of treatment.
These factors significantly reduce access to care, and studies have shown that when access to
care is low, many couples will choose to use unprotected intercourse, even if counseled on
the risks involved. Without appropriate screening and counseling, unprotected intercourse is
risky, with 4% of women becoming infected in one study

Pre-exposure prophylaxis (PrEP) is a treatment taken by the woman before having unprotected
intercourse with an infected man. The U.S. Food and Drug Administration (FDA) has approved
the drug Truvada (Tenofovir/emtricitabine) for use by HIV-discordant couples. Whereas IVF and
ICSI are invasive techniques that breach the natural barriers to infection in the female
reproductive tract, intercourse preserves these protective mechanisms. The goals of treating
HIV-discordant couples are to reduce the infectivity of the male and the susceptibility of
the female to infection. Trials carried out primarily in Africa looking at HIV transmission
in HIV-discordant couples have shown that use of PrEP significantly reduces the risk of
transmission. Based on these results, the U.S. Centers for Disease Control and prevention
(CDC) has recommended that serodiscordant patients who wish to have a child be counseled on
the availability of PrEP. When risks of transmission are minimized, including undetectable
HIV in blood and the use of PrEP, unprotected intercourse during the fertile period is likely
to be a safe option for conceiving a child.

An ongoing Swiss trial, started in 2004, has had no infection of the female in 53 couples,
and has had an overall pregnancy rate of 75% after 6 cycles of treatment. Preliminary data
from a United Kingdom trial reports 13 couples with 11 pregnancies and no female infection.
An Italian trial has been initiated recently. Treatment of HIV-discordant couples with PrEP
and timed, unprotected intercourse remains experimental.

The investigators propose to enroll HIV-discordant couples who have been counseled on the
safer alternatives of donor insemination, adoption and remaining childless; have been offered
referral to a clinic offering sperm washing with insemination or ICSI; have been apprised of
the risks of using PrEP and one timed intercourse per cycle; and decide to proceed with this
method. Couples will be from the population of HIV-discordant patients with a minimal risk of
disease transmission as described above. After evaluation for normal fertility and low
potential for disease transmission, the couple will receive instruction on timing of the most
fertile day of the cycle, and the woman will be given a prescription for the PrEP medication.
The woman and any offspring will be followed for 6 months using blood tests to check for
evidence of HIV infection.

Inclusion Criteria:

Woman:

- 18-40 years of age

- not pregnant

- BMI 18.5-30

- nonsmoker

- no use of IV drugs

- seronegative for HIV

- negative tests for hepatitis C and hepatitis B, human T-lymphotropic virus (HTLV
I&II), syphilis, Chlamydia trachomatis and Neisseria gonorrhea

- normal fertility examination

- normal PAP smear and HPV screen

Man:

- 18-50 years of age

- nonsmoker

- no use of IV drugs

- HIV-seropositive

- under the care of an infectious disease specialist

- without evidence of acquired immunodeficiency syndrome (AIDS)

- HIV viral load <50,000 copies/mL and CD4 count > 250 cells/mL for the preceding 6
month period

- taking anti-retroviral medication

- must be circumcised

- have 2 normal semen analyses

Couple:

- must be informed of safer choices (donor insemination, adoption, remaining childless)

- must attest to safe sexual practices.

Exclusion Criteria:

- either man or woman is incarcerated

- either man or woman is unable to provide informed consent

- woman is unable to take Truvada (tenofovir/emtricitabine) medication due to
contraindications or adverse reaction