Clinical trial NCT02572505: Pre-Exposure Prophylaxis and Timed Intercourse for HIV-Discordant Couples
Official title: Pre-Exposure Prophylaxis and Timed Intercourse for HIV-Discordant Couples
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: HIV
Infertility
Keywords: HIV-Discordant
Preexposure Prophylaxis
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
First posted: 2015-10-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 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 United States have been resistant to treating HIV-discordant couples, offering only expensive, invasive techniques. This reduces access to care, leading to couples choosing unprotected intercourse to conceive a child. Pre-exposure prophylaxis (PrEP) is a treatment taken by the woman before having unprotected intercourse with an infected man. Truvada has been approved by the Food and Drug Administration (FDA) to reduce the risk of HIV-discordant couples and the 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 use of PrEP, unprotected intercourse during the fertile period is likely to be a safe option for conceiving a child. 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 in vitro fertilization (IVF); 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of women remaining HIV-seronegative for 6 months after a treatment menstrual cycle
timeFrame: 6 months after each menstrual cycle in which HIV-discordant couple has one act of unprotected intercourse
Secondary outcomes:
measure: Proportion of couples achieving pregnancy after each treatment menstrual cycle.
timeFrame: Approximately one month after unprotected intercourse
Other outcomes:
Locations:
city: Columbia
country: United States
facility: Missouri Center for Reproductive Medicine & Fertility
state: Missouri
Study officials:
affiliation: University of Missouri-Columbia
name: Danny J Schust, M.D.
role: PRINCIPAL_INVESTIGATOR
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