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Many HIV-discordant couples express a strong wish to conceive a child. Insemination with processed semen is offered to these couples in many countries. Given the very low level of transmission risk during fully suppressive antiretroviral therapy, we offered timed intercourse combined with preexposure prophylaxis to further reduce the transmission risk. In 53 cases, natural conception was attempted using the proposed method. Pregnancy rates were high and reached a plateau of 75% after six cycles. Advanced age in the female partner was a predictor for infertility in these couples.