Safer Conception Strategies for HIV-Serodiscordant Couples: How Safe Is Safe Enough?

With access to antiretroviral therapy (ART), human immunodeficiency virus (HIV)–infected men and women are living longer and healthier lives and have childbearing desires similar to those of HIV-unaffected individuals [1]. Many are in HIV-serodiscordant sexual partnerships (with an HIV-uninfected partner), and attempts at conception confer sexual HIV transmission risk [2]. HIV risk reduction strategies are available for HIV-serodiscordant couples, in which the male is infected, who want to conceive (Table 1), but there are limited data to inform which or how many concurrent methods a couple should adopt. ART for the HIV-infected male partner is recommended regardless of conception plans, to reduce HIV transmission risk to partners and improve the man’s own health [11, 12]. Because adherence to ART is imperfect and genital shedding of HIV may occur even in the presence of suppressed plasma viral load, couples may seek additional methods to reduce transmission risk. For an uninfected woman wishing to conceive with an infected male partner who is receiving ART, oral preexposure prophylaxis (PrEP) may be a valuable option, particularly if use of ART or ART adherence by the male partner is limited. Combining PrEP for the female partner (oral tenofovir/emtricitabine, or TDF/ FTC) – with ART administration to the male partner for safer conception has been acceptable in observational studies [13–15]. Because PrEP trials were conducted without receipt of ART by the infected partner and ART trials were conducted without receipt of PrEP by the uninfected partner, there are no direct clinical data to estimate the benefit of using PrEP and ART together to decrease periconception HIV transmission risk, compared with either intervention alone. In this issue of The Journal of Infectious Diseases, Hoffman et al use a thoughtfully designed simulation model to investigate the role of PrEP, ART, or both in male-infected, HIV-serodiscordant couples who are attempting to conceive. When clinical data are limited, simulation models can help to inform decision-making. If multiple studies provide partial information, a single model can integrate available data. When data are equivocal or missing, investigators make explicit assumptions about which values to use in a model and then vary these values in sensitivity analyses to identify the thresholds at which decisions would change; this allows readers to understand whether more data are needed to accurately inform clinical choices [16]. Here, Hoffman et al combine transmission risks from separate PrEP trials, ART-as-prevention trials, and observational studies of age-stratified pregnancy rates, and conduct extensive sensitivity analyses on key model parameters. They focus this analysis on couples who maintain the high rates of ART-mediated viral suppression and PrEP adherence seen in the HPTN 052 and Partners PrEP trials [3 ,5, 17, 18]. They also assume that both partners are aware of each others’ HIV status, have been screened and treated for sexually transmitted infections (STIs), and have completed normal fertility evaluations. There are 3 primary messages from their analysis. First, if couples limit condomless sex to the 2 days before and the day of ovulation, and if the male partner is receiving virally suppressive ART, PrEP for the female partner provides little additional benefit. The authors define a “successful” outcome as one in which the female partner remains uninfected and a full-term pregnancy occurs. With ART alone, the yearly chance of this successful outcome is 29.1%; with ART plus PrEP, this chance is 29.2%, which is essentially equivalent within the margin of error of the model results. Second, if couples choose a single intervention, ART for the male partner is projected to be more effective in reducing transmission than PrEP for the female Received and accepted 5 May 2015; electronically published 19 June 2015. Correspondence: Andrea L. Ciaranello, MD, MPH, Division of Infectious Diseases, Massachusetts General Hospital, 50 Staniford St, Rm 936, Boston, MA 02114 (aciaranello@ partners.org). The Journal of Infectious Diseases 2015;212:1525–8 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of thework, in anymedium, provided theoriginalwork is not altered or transformed in anyway, and that thework is properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/infdis/jiv275