John and Sally (not their real names) were married 2 years ago and were recently referred to me when John found out that he was HIV positive. He had a plasma HIV-1 RNA of 91,000 copies/mL and CD4+ cell count of 631 cells/mm3. John has been asymptomatic and Sally has been repeatedly HIV antibody negative. To their knowledge, there have been no high-risk exposures during the past 6 months, although they admit that condom use has not been 100%.
They were referred to me to address their seemingly simple questions regarding Sally’s risks of acquiring HIV from John, how they can minimize the risks, and whether they will ever be able to safely have a child together.
Starting Antiretroviral Therapy
I always start with the easy question, so I suggested latex condoms for all sexual episodes and reminded Sally to avoid contact with John’s blood. I further discussed with them the data from HPTN 052, explaining that among the serodiscordant couples in this trial, treating the infected partner with antiretrovirals in conjunction with standard safe sex practices resulted in a 96% reduction in risk of their partner becoming infected with HIV. These data, along with the benefits of antiretroviral therapy for John, made it by far my preferred option among any treatment choices.
Role of PrEP
However, to provide the complete picture, I thought it important to also describe the recent US Food and Drug Administration approval and interim Centers for Disease Control and Prevention guidelines for use of tenofovir/emtricitabine for pre-exposure prophylaxis (PrEP). After considering this information, they wondered whether it might be a better option to have Sally take PrEP rather than rushing John into treatment, or to have Sally take PrEP along with John taking antiretroviral therapy.
I responded that treating John is good for both of them. In addition, I explained that treating Sally with PrEP alone will reduce her acquisition risk but probably to a lesser extent than will treating John (there was a relative reduction of 75% in the overall population in the incidence of HIV infection with tenofovir/emtricitabine in the Partners PrEP trial; 66% in women). In addition, PrEP will not address John’s health risks from untreated HIV and puts Sally at real risk for short-term and long-term toxicity (that could include gastrointestinal effects and fatigue[3-5] and decline in bone mineral density.) Finally, I shared with them that we simply have no data to inform us how much additional protection Sally will derive from receiving PrEP if John’s viral load is suppressed on an antiretroviral regimen. In summary, I told them that my personal view is that as long as John’s viral load is well controlled on treatment, I am not convinced that the theoretical benefits of adding continuous PrEP outweigh the potential risks.
Strategies for Conception
John and Sally were also very focused on whether they would be able to have children. We discussed using donor sperm, and that was not an acceptable option for them. I also explained the concept of sperm washing with or without intracytoplasmic sperm injection, but financially these procedures were out of their reach. Finally we talked about alternative strategies that—although not as carefully studied—would likely be associated with low risk of transmission, recognizing that there may be some small but residual risk. We discussed the strategy of Sally taking PrEP and selectively discontinuing condom use during specific periods when they were trying to conceive. I explained that the risk of HIV transmission would be small if John’s viral load were suppressed on antiretroviral therapy before they attempted pregnancy and perhaps further reduced if Sally were also receiving PrEP. In this scenario, the combination prevention strategy of PrEP and antiretroviral therapy might provide additional protection for Sally while limiting her exposure to PrEP to the weeks or months that they are trying to conceive. So that they could think about this at greater length and further discuss the possibilities, I reprinted the discussion on this topic that has been recently added to the Department of Health and Human Services Perinatal Guidelines.
Although I wish I had all of the answers for couples such as John and Sally, I do feel that I have a lot more data to share today than I did even 6 months ago. How would you have advised them? Do you see a role for the combination of antiretroviral therapy and PrEP in serodiscordant couples? Please share your perspectives by leaving a comment below.
Eric S. Daar, MD, is Chief, Division of HIV Medicine at Harbor-UCLA Medical Center, and Professor of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
Dr. Daar has disclosed that he has received funds for research support from Abbott, Gilead Sciences, Merck, Pfizer, and ViiV and consulting fees from Bristol-Myers Squibb, Gilead Sciences, Merck, and ViiV.
1. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505.
2. Centers for Disease Control and Prevention. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb Mortal Wkly Rep. 2012;61:586-589
3. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399-410.
4. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention. N Engl J Med. 2011;364:1373.
5. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423-434.
6. Quinn TC, Wawer JW, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med. 2000;342:921-929.
7. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1- infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed September 24, 2012.