title: HIV-serodiscordant couples desiring a child: 'treatment as prevention,' preexposure prophylaxis, or medically assisted procreation?
abstract: OBJECTIVE
  We sought to assess the residual risk of HIV transmission, cost, and cost-effectiveness of various strategies that can help fertile HIV-uninfected female/HIV-1-infected male on combination antiretroviral therapy with plasma HIV RNA <50 copies/mL couples to have a child: (1) unprotected sexual intercourse (treatment as prevention); (2) treatment as prevention limited to fertile days (targeting fertile days); (3) treatment as prevention with preexposure prophylaxis (tenofovir/emtricitabine); (4) treatment as prevention and preexposure prophylaxis limited to fertile days; or (5) medically assisted procreation (MAP).
  
  
  METHODS
  This was a model-based, cost-effectiveness analysis performed from a French societal perspective. Input parameters derived from international literature included: 85% probability of live births in different strategies, 0.0083%/mo HIV transmission risk with unprotected vaginal intercourse, 1% HIV mother-to-child transmission rate, and 4.4% birth defect risk related to combination antiretroviral therapy when the mother is infected at conception. Targeting fertile days and preexposure prophylaxis were estimated to decrease the risk of HIV transmission by 80% and 67%, respectively, and by 93.4% for preexposure prophylaxis limited to fertile days (the relative risk of transmission considering the combination of both strategies assuming to be (1-80%)*(1-67%) = 16.6% in basecase). Tenofovir/emtricitabine monthly cost was set at €540.
  
  
  RESULTS
  The HIV transmission risk was highest with treatment as prevention and lowest for MAP (5.4 and 0.0 HIV-infected women/10,000 pregnancies, respectively). Targeting fertile days was more effective than preexposure prophylaxis (0.9 vs 1.8) and associated with lowest costs. Preexposure prophylaxis limited to fertile days was more effective than targeting fertile days (0.3 vs 0.9) with a cost-effectiveness ratio of €1,130,000/life year saved; MAP cost-effectiveness ratio when compared with preexposure prophylaxis limited to fertile days was €3,600,000/life year saved. Results were robust to multiple sensitivity analyses.
  
  
  CONCLUSIONS
  Targeting fertile days is associated with a low risk of HIV transmission in fertile HIV-uninfected female/male with controlled HIV-1 infection couples. The risk is lower with preexposure prophylaxis limited to fertile days, or MAP, but these strategies are associated with unfavorable cost-effectiveness ratios under their current costs.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Infection Antimicrobials Modelling & Evolution (IAME), unity 1137, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France. Electronic address: guillaume.mabileau@inserm.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mabileau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Infection Antimicrobials Modelling & Evolution (IAME), unity 1137, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzinger
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Infection Antimicrobials Modelling & Evolution (IAME), unity 1137, Paris, France; Mailman School of Public Health, Columbia University, New York, NY.
authors.forename: Juan
authors.initials: J
authors.lastname: Flores
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Reproductive Biology, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Patrat
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Obstetrics and Gynecology, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Departement Hospitalo-Universitaire Risk and Pregnancy, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Luton
authors.affiliation: Department of Obstetrics and Gynecology, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Epelboin
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Departement Hospitalo-Universitaire Risk and Pregnancy, Paris, France; Department of Obstetrics and Gynecology, Louis Mourier Hospital, AP-HP, Colombes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Infection Antimicrobials Modelling & Evolution (IAME), unity 1137, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Infectious Diseases, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Matheron
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Infection Antimicrobials Modelling & Evolution (IAME), unity 1137, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Infectious Diseases, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D046910:Fertile Period; D005602:France; D015658:HIV Infections / Q000191:economics / Q000517:prevention & control* / Q000635:transmission; D017048:Health Care Costs; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000191:economics / Q000517:prevention & control*; D007315:Insemination, Artificial; D008297:Male; D018803:Models, Economic; D063065:Organophosphonates / Q000191:economics / Q000627:therapeutic use; D065129:Pre-Exposure Prophylaxis / Q000191:economics*; D011247:Pregnancy; D027724:Reproductive Techniques, Assisted / Q000191:economics*; D012661:Semen / Q000821:virology; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
keywords: HIV; cost-effectiveness; postexposure prophylaxis; pregnancy; reproductive techniques; transmission