Presentation

Human immunodeficiency virus (HIV) infects individuals of any age. In 2017, men and women of reproductive age (13–44 years) comprised the largest group living with HIV; 19% of those infected with HIV were women. With early diagnosis and improved treatment, HIV has changed from a terminal, life-threatening condition to a chronic, manageable disease with an overall good prognosis for many individuals.

Many men and women with HIV infection desire biological children, justifying the need for appropriate and timely preconception counseling. This counseling must include discussion of methods to minimize risk of seroconversion in uninfected partners while optimizing chances of conception.

A critical part of counseling is a review of the risks of HIV transmission. The baseline risk of HIV transmission in male-positive serodiscordant couples has been estimated to be 1 in 500–1000 episodes of condomless intercourse. Risk factors for seroconversion of an uninfected partner include higher viral load, genital infection, inflammation, or abrasions. One large randomized controlled trial demonstrated a seroconversion risk of 1.2 per 100 person-years, with a decrease in seroconversion with early initiation of antiretroviral therapy by the person living with HIV. A meta-analysis estimated a seroconversion risk of 0.03–0.06 per 10,000 episodes of intercourse, with the use of antiretroviral therapy and condoms .

Preexposure prophylaxis (PrEP) use by the uninfected partner has also been shown to minimize the risk of seroconversion. In one study of male-positive serodiscordant couples using antiretroviral therapy and PrEP combined with condomless intercourse timed to ovulation, no seroconversions were noted and the pregnancy rate was 75%, demonstrating the benefit of the combination of antiretroviral therapy and PrEP with condomless timed intercourse in minimizing HIV infection rates.

One large, prospective, multicenter observational study included 888 HIV serodiscordant couples having condomless intercourse on antiretroviral therapy. No HIV transmissions were noted within the couples. Another large study from Kenya including 4747 HIV serodiscordant couples demonstrated no HIV transmission after 6 months of antiretroviral therapy. Of note, greater than 80% of persons with HIV receiving treatment have undetectable viral loads.

Based on these data, the Centers for Disease Control and Prevention (CDC) released a memo stating there was “effectively no risk” of HIV transmission to an HIV-negative partner if the HIV positive patient was virally suppressed, defined as less than 200 copies/mL or undetectable. This furthered the Prevention Access Campaign’s undetectable equals untransmittable (U = U) initiative, encouraging use of antiretroviral therapy, and improving the quality of life and health care for HIV patients. Providers of preconception care may use this reassuring data to discuss intercourse timed to the fertile window as an option for conception for couples with low suspicion for infertility, thereby reducing the barriers to reproductive care previously encountered by these patients.

Historical context

The new recommendations endorsing condomless intercourse in serodiscordant HIV couples are a large shift from prior recommendations. In 1988, the CDC recommendations stated that donation of any specimen from an HIV-positive person was not endorsed unless needed in an emergent situation without alternatives; these initial recommendations were interpreted as forbidding intrauterine insemination (IUI) with sperm from a person infected with HIV, given the fear of seroconversions in uninfected partners.

Subsequently in 1994, the American Society of Reproductive Medicine (ASRM) encouraged providers to review the consequences of infected sperm and discuss the limited options available, including use of donor sperm, adoption, or not having children. These recommendations created challenges for persons living with HIV who desire future childbearing because American practitioners could cite the recommendations against timed intercourse and assisted reproductive technology, thus limiting treatment options.

Over the following years, as HIV care was improving, patients were experiencing improvement in overall health, turning HIV into a manageable, chronic condition with early antiretroviral treatment extending life expectancy. At the same time, a decline in the rates of vertical transmission was seen, largely because of early antenatal initiation of antiretroviral therapy. Other key contributing factors include cesarean delivery for patients with an elevated viral load, administration of neonatal antiretroviral therapy for those at highest risk, and elimination of breastfeeding postpartum. Despite the improvement in overall health and reduced perinatal transmission risks, barriers to reproductive care for persons living with HIV persisted.

As technology improved, sperm-washing techniques with assisted reproductive technology became a viable option for HIV male-positive serodiscordant couples. The swim-up and density gradient centrifugation techniques for sperm washing were used to remove the virus from the semen specimen and consequently concentrate live, motile sperm for IUI or in vitro fertilization (IVF).

Restricted by the CDC and ASRM guidelines, the reproductive care for HIV patients in the United States focused on IVF with intracytoplasmic sperm injection after sperm-washing techniques for male-positive serodiscordant couples. A 10 year single-center, retrospective study included 420 IVF cycles after sperm washing, resulting in 116 deliveries; no maternal or neonatal HIV infections were reported.

Meanwhile, in Europe, intrauterine insemination of prepared sperm using similar washing techniques was the preferred method of conception for HIV male-positive serodiscordant couples. One small Italian study including 29 male positive serodiscordant couples assessing the efficacy of IUI following these sperm preparation techniques demonstrated no female seroconversions; also notably, of the 10 live births, no perinatal infections were diagnosed. These studies supported sperm washing with IUI and IVF as safe and effective methods for conception, but access to care and high costs limited their availability to many HIV serodiscordant couples.

In 2015, the ASRM updated its guidelines to encourage providers to evaluate HIV serodiscordant couples and offer fertility treatment to persons living with HIV. ASRM guidelines specifically recommended IUI or IVF to avoid seroconversion in uninfected partners and offspring. The guidelines also discussed timed intercourse with use of antiretroviral therapy but reported “this practice is not recommended.” Even with the 2015 ASRM guidelines, reproductive care has been limited to expensive assisted reproductive technology options for persons living with HIV, especially for male-positive serodiscordant couples.

Current recommendations

In 2017, nearly 30 years since its initial recommendations, the CDC published updated recommendations. These new CDC guidelines endorse sperm preparation techniques followed by IUI or IVF/intracytoplasmic sperm injection for persons infected with HIV, in conjunction with antiretroviral and PrEP therapies. The CDC also clearly stated new recommendations to support condomless intercourse timed to ovulation as an option in individuals suppressed on antiretroviral therapies.

The U = U campaign and CDC memo support condomless intercourse for couples in whom the HIV infected individual has undetectable viral loads. These encouraging new recommendations will further the initiative to expand reproductive options available to HIV serodiscordant couples; these options include counseling on condomless intercourse timed to a window of peak fecundability occurring 1–2 days prior to ovulation.

Following a discussion regarding risks of HIV transmission, providers should counsel male-positive HIV serodiscordant couples on the following options: (1) intercourse timed to ovulation or (2) sperm washing followed by either IUI or IVF. The U = U initiative would also support condomless intercourse for female-positive HIV serodiscordant couples as a method to conceive a pregnancy if the viral load is undetectable on treatment to minimize infection of the partner and pregnancy. Other options include insemination, with either washed sperm in an office setting or unprepared sperm in a home setting.

Discussion of antiretroviral therapy for the person with HIV and PrEP for the uninfected partner is a critical piece of counseling. Although sperm washing followed by either IUI or IVF is also part of the current CDC recommendations, for many HIV serodiscordant couples, we should not prioritize these approaches for initial attempts at conception.

In conclusion, women and men living with HIV who desire biological offspring must be educated and counseled on all available reproductive options. For most couples for whom the concern for infertility is low, optimization of HIV care and other medical conditions in addition to a thorough review of medications should be completed with the patient’s HIV provider.

Preconception counseling must include discussion of the risks of HIV transmission to the uninfected partner and pregnancy, followed by counseling on condomless intercourse restricted to the fertile window. This counseling may be provided, without the assistance of a reproductive endocrinology and infertility specialist. If concern for infertility is present, however, then referral to a reproductive endocrinology and infertility provider would be necessary to complete the evaluation and discuss options, which may include assisted reproductive technology techniques.

For individuals who are unwilling to accept any, even if minimal, risk of viral transmission to an uninfected partner, the options include use of donor gametes and possibly a gestational carrier, adoption, or having no children.

On a final note, it is our duty as women’s health providers to assist in breaking down barriers to reproductive health care for this vulnerable population and provide all reproductive options available to optimize the chance of family building to meet our patient’s goals.