Can a serodifferent (HIV serodiscordant) couple in a mutually monogamous relationship safely conceive and stop using condoms if the partner with Human Immunodeficiency Virus (HIV) is on effective Antiretroviral Therapy (ART) and has an undetectable HIV Ribonucleic Acid (RNA) level?

U=U and Safe Conception for Serodiscordant Couples

If the partner with HIV is on antiretroviral treatment and their HIV RNA level has been undetectable for six months, there is effectively no risk of sexual transmission, making Answer A the correct advice for this couple. 1

Evidence Supporting U=U (Undetectable = Untransmittable)

The most robust evidence demonstrates that viral suppression eliminates sexual HIV transmission:

• Treatment as prevention with sustained viral suppression for 6 months eliminates sexual transmission risk when the HIV-positive partner maintains an undetectable viral load 1
• The PARTNER Study documented zero linked HIV transmissions over 894 couple-years of observation among serodiscordant couples engaging in condomless sex when the HIV-positive partner was virologically suppressed on ART 2
• The HPTN052 study demonstrated that ART reduced HIV transmission by more than 96% in serodiscordant couples 2
• More recent prospective cohort data from 161 HIV-serodiscordant couples attempting natural conception showed zero cases of sexual or vertical HIV transmission when the infected partner maintained viral suppression for at least 6 months 3

Why Answer A is Correct and Others Are Wrong

Answer B (3 months) is incorrect because guidelines consistently specify 6 months of sustained viral suppression as the threshold for eliminating transmission risk 1. The 3-month timeframe is insufficient to ensure durable suppression.

Answer C is incorrect because U=U has been extensively studied in heterosexual serodiscordant couples, not just MSM populations. The natural conception studies specifically involved heterosexual couples attempting pregnancy 3, 4

Answer D is incorrect because U=U was proven for sexual transmission prevention, not vertical transmission. The concept specifically addresses sexual transmission risk when viral suppression is achieved 1, 2

Practical Recommendations for This Couple

Prerequisites Before Attempting Natural Conception

The HIV-positive partner must meet these criteria before attempting conception 3, 4:

• On ART with persistent plasma viral suppression for at least 6 months 3
• ART adherence over 95% 3
• Preserved immune status 3
• If male is the infected partner: undetectable HIV viral and proviral load in semen 3
• Both partners screened and treated for any sexually transmitted infections 1
• Absence of fertility problems in both partners 3

Optimizing Conception Timing

For serodiscordant couples attempting natural conception 1, 3:

• Use ovulation predictors to limit unprotected intercourse to peak fertility periods 1
• The pregnancy rate averages 1.9 per 100 acts of vaginal intercourse with mean time to conception of 6.1 months 3
• Continue consistent condom use except during fertile window attempts 1

Additional Risk Reduction Strategies

If the male partner is HIV-positive and female is uninfected 1:

• Screen and treat both partners for STDs to minimize genital ulcers and genital tract HIV load 1
• Perform semen analysis to exclude abnormalities that might preclude conception 1
• Consider pre-exposure prophylaxis (PrEP) for the uninfected female partner during conception attempts 1, 5, 6

If the female partner is HIV-positive and male is uninfected 1:

• Home artificial insemination (vaginal insertion of ejaculate with a syringe) effectively avoids risk to the uninfected male partner 1
• Otherwise maintain consistent condom use 1

Critical Caveats and Monitoring

Ongoing Viral Suppression is Essential

• The HIV-positive partner must maintain undetectable viral loads throughout conception attempts and pregnancy 1, 3
• HIV RNA monitoring should occur every 3 months until suppressed for at least 1 year, then can be reduced to every 6 months if clinically stable 1
• Any detectable viral load requires immediate reassessment of adherence and repeat testing 1

Common Pitfalls to Avoid

• Do not assume zero risk exists if viral suppression has not been sustained for the full 6 months 1, 3
• Inconsistent ART adherence can lead to viral rebound and increased transmission risk 2, 3
• Do not recommend spermicides, as these increase HIV transmission risk 1, 7
• Avoid medications with reproductive toxicity during conception attempts, particularly efavirenz which has teratogenic effects 1

Pregnancy Considerations

Once pregnancy is achieved 1:

• Continue ART throughout pregnancy to prevent vertical transmission 1
• The HIV-infected mother should not breastfeed to minimize vertical transmission risk 1
• The infant should receive appropriate post-exposure prophylaxis 1