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 men who have sex with men. The evidence base includes both male-infected and female-infected heterosexual partnerships 2, 3

Answer D is incorrect because U=U specifically applies to sexual transmission prevention. While vertical transmission prevention requires additional interventions, the U=U principle was established primarily through studies of sexual transmission 1, 2

Practical Recommendations for This Couple

Prerequisites for Safe Conception

Before attempting natural conception, ensure the following conditions are met:

• The HIV-positive partner must have sustained viral suppression (undetectable HIV RNA) for at least 6 months 1, 3
• ART adherence must exceed 95% 3
• The HIV-positive partner should have preserved immune status 3
• Both partners should be screened and treated for sexually transmitted infections to minimize genital tract HIV load 1
• For male HIV-positive partners, confirm undetectable HIV viral and proviral load in semen 3
• Assess for fertility problems in both partners 3

Conception Strategies Based on Partner Status

If the male partner is HIV-positive:

• Natural conception with timed intercourse during peak fertility is safe when viral suppression criteria are met 1, 3
• Use ovulation predictors to optimize timing and limit unprotected intercourse to fertile periods 1
• Consider pre-exposure prophylaxis (PrEP) for the female partner as an additional layer of protection during the conception period 4, 5

If the female partner is HIV-positive:

• Home artificial insemination (vaginal insertion of ejaculate with a syringe) effectively avoids any risk to the uninfected male partner 1, 6
• Natural conception is also safe when viral suppression criteria are met 3

Monitoring During Conception Attempts

• Continue regular viral load monitoring every 3-6 months to ensure sustained suppression 1
• Maintain ART adherence throughout conception attempts and pregnancy 1
• The HIV-negative partner should undergo HIV testing every 3-6 months 2

Important Caveats

Do not discontinue condoms prematurely: While U=U eliminates HIV transmission risk, condoms provide protection against other sexually transmitted infections, which can increase HIV transmission risk if they occur 1, 2

Viral suppression must be sustained: A single undetectable viral load is insufficient. The 6-month threshold ensures durable suppression and minimizes risk of viral rebound 1, 3

Medication adherence is critical: Inconsistent ART adherence can lead to viral rebound and restore transmission risk 3, 5

Avoid certain medications if pregnancy is possible: Efavirenz has been associated with teratogenic effects and should be avoided in women trying to conceive 1

Spermicides are contraindicated: These have been associated with increased HIV transmission risk and should never be recommended 1, 6