Sero discordant HIV infected couples …discussion for Pre Exposure Prophylaxis (PrEP)for an uninfected partner, Anti Retroviral Therapy (ART) for infected partner or both

PrEP, ART, or Both? How I Advised a Serodiscordant Couple

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.[1] 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).[2] 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).[3] 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.[5]) 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[6] 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.[7]

Your Thoughts?
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: Accessed September 24, 2012.


I take 6 months approximately to treat male HIV-positive man with ART. And once he is investigated and treated for other sexually transmitted diseases, I prescribe TDF + FTC combination pill before and after Intra Uterine Insemination (IUI) to uninfected partner. Results are promising after 3 IUI.
Dr Raj Harjani Mumbai INDIA – 2/3/2013 
Responses (1)


Cool. Did we get the confimation levels of viral loads before IUI?
Dr Adegboye, NIGERIA – 2/17/2013 
Responses (1)


We confirm with plasma viral load. once undetectable for at least 2 months, then we consider person fit for sperm wash. Generally all male serodiscordant couples achieve undetectable levels by 4 months.
Dr Raj Harjani Mumbai INDIA – 2/25/2013


In my practice, I have several times come across discordant couples. But the difference with John and Sally’s case is that over 90% of my cases have been HIV advanced with children and irregularly practicing protected sex. We are living in a gender inequality culture where sex practice is male initiative, while woman, regardless her HIV status has no power to oppose her partners choice in term of safer sex practice. In our experience, women are more adherent to treatment than men. At our ARTClinic, discordant couples coming together for review can be estimated as less than 5%, among them those preoccupied about having safely children. We attempt to encourage them to report for routine review visits at ART clinic as a couple for proper IEC (information, education and communication) more especially for discordant couples. The concept of PrEP for uninfected HIV partner is not yet in practice in our ART clinic. We need to start now this important program targeting the concerned couples.
muhemedi – 1/17/2013 


I love Joels categorization of the 3 approaches and will quote it widely.
David A. Wohl, MD – 11/11/2012 


This question just came up with a male patient of mine who is suppressed and wants to have a child with his HIV-negative wife. They have been scrupulous about using condoms. I described 3 approaches, which I called “safe,” “extremely safe,” and “ridiculously safe.” The “safe” approach is to have unprotected intercourse during times of maximum fertility (determined by home ovulation monitoring), based on the fact that suppressive ART was 96% effective in HPTN 052 (and having an undetectable viral load was 100% effective, something that is less often mentioned). The “extremely safe” approach is to add courses of PrEP for his wife during times of attempted conception. The “ridiculously safe” approach is to use sperm washing. My patient and his wife are inclined to take the middle approach, which seems like a good choice to me. Some have also suggested conceiving by home artificial insemination with a syringe rather than actual intercourse to reduce vaginal trauma, though this seems unnecessary if you’re combining ART and PrEP.
Joel E. Gallant, MD, MPH – 10/29/2012 


This is an interesting clinical scenario encountered frequently, and providing concrete answers through data support and clinical trials will definitely help couples to make decisions, and help consulting and treating physicians to provide more precise data for that purpose.
Doctor “T” – 10/24/2012 
Responses (1)


I agree with Dr T. One question is whether the belt and suspenders approach of ART for him and PrEP for her would offer anything more than ART for John alone? The calculus gets more complex when adding in potential toxicity of tenofovir in Sally (reduced BMD, for instance) and financial cost of PrEP. Short term use during attempts at conception may be more feasible. For the couples I have seen (most often an HIV+ patient of mine and his uninfected partner), the major issue has been access as these folks have no insurance.
David A. Wohl, MD – 10/28/2012 


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