The Debate Continues: Does "Undetectable" Mean "Uninfectious"?

One of the most provocative sessions of the XVII International AIDS Conference (AIDS 2008) likely took place before the conference even officially began. In a charged satellite event, a panel of researchers and a huge audience took part in a debate over whether it's safe for an HIV-infected person in a monogamous relationship to have unprotected sex with an HIV-uninfected partner, provided the HIV-infected person has an undetectable viral load, is on stable antiretroviral therapy (ART) and has no sexually transmitted diseases (STDs).

In this summary at the end of the satellite event, Bernard Hirschel, M.D., of the University Hospital in Geneva, recaps the major points. Dr. Hirschel is one of the physicians who inadvertently ignited this controversy in February 2008 by helping author the now-infamous "Swiss statement," which you'll read about in a moment.

Bernard Hirschel, M.D.

[In addition to Dr. Hirschel's talk, you should also read the transcript of this lengthy, but fascinating, question-and-answer session with the audience.]

I'm not a member of the [Swiss] Federal Commission [for AIDS-related Issues]. I'm guilty by association. I have for a long time been a fan of Julio [Montaner]'s, particularly since his talk at the Toronto [International AIDS] Conference.¹ What we need are new methods for prevention. Vaccines are a pie in the sky. Microbicides have not worked so far. We have circumcision; that's partly effective.^2,3 We do have treatment, and we need treatment for prevention.

Pietro Vernazza explained to you what the Swiss statement is.⁴ It's directed at physicians. It is of help in counseling. It evaluates the relative risks of sex on HAART [highly active antiretroviral therapy] without condoms versus sex off HAART with condoms.⁵ And it is very tightly qualified: on HAART for at least six months, consistently undetectable viral load, no STDs, and perfect adherence. The Swiss statement does not advise against condoms and does not condone unsafe sex.

Behind the Swiss statement is the general idea that all risks are created equal, and that there is a problem when equal risks are unequally treated. Because how can one permit sex with condoms, untreated, while prescribing sex without condoms, treated, when the latter is equally or less risky than the former? I have not yet found an answer to this question.

Myron Cohen pointed out the great biological plausibility and that certainty is very difficult to come by.⁶ Events are rare and there are many confounding influences, such as the pharmacology of ARVs [antiretrovirals]. His pioneering study of discordant couples will give us some of the numbers we need, but will take a long time.⁷

Nancy Padian looked at the Swiss statement from the women's standpoint.⁸ She finds pros and cons, states that compliance with condoms is disappointing, and points out the issues related to power and gender.

Nikos [Dedes], from the standpoint of the people living with HIV and AIDS, states that⁹ the conscience of being infectious is a heavy burden to carry, and lifting it off is taking a load off of HIV-positive people. There are other issues: regaining the right to uninhibited intimacy, procreation, and -- a fact that I very strongly believe myself -- that being less infectious will reduce stigma and discrimination.

Catherine Hankins points out that first-world views are called the truth,¹⁰ and that most HIV-infected patients have no access to viral load testing and to diagnose STDs. It is therefore doubly difficult to, quote-unquote, be sure about ends of risk in less developed countries. The Swiss statement will find its first application in pregnancy planning, perhaps complemented by pre-exposure prophylaxis, but has little applicability to other situations where condom promotion, in combination with treatment and circumcision, must remain the rule.

Let me now hazard into the difficult fields of politics and philosophy. What do we do when we, as a panel, make recommendations? Well, we have to cope with what I would call the asymmetry of risk. To say that something is dangerous while in reality it is not has no consequences for the politician or the panel member who says so. The opposite, however, to say that something is not dangerous and then something bad happens is, at times, career-ending. Therefore, there is a natural tendency of panels and commissions to, first and foremost, protect themselves.

One way of protecting themselves is to ask for more evidence. But the time it takes to obtain perfect evidence has a great cost. Remember that for circumcision, between good circumstantial evidence^11,12 that it worked and the acceptance through a randomized controlled trial,³ 17 years elapsed. No offense meant to my attractive fellow panelists, but there is one sure thing at every World AIDS conference, and that is that the panelists are two years older. Of course, I'm part of them. And their sex lives are largely behind them. So I think we should take heed from that venerable institution, the Catholic Church, and make a second Swiss statement: Let us not be AIDS cardinals.

This transcript has been lightly edited for clarity.

References

1. Montaner J. Re-evaluating the cost-effectiveness of HAART -- the case for expanding treatment access to curb the growth of the epidemic. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract WEPL01.
   View slides: Download PowerPoint

2. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 trial. PLoS Med. November 2005;2(11):e298.

3. Quinn TC. Circumcision and HIV transmission. Curr Opin Infect Dis. February 2007;20(1):33-38.

4. Vernazza P. Summary of the Geneva's closed hearing on HIV transmission under ART. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract SUSAT4104.
   View slides: Download PowerPoint

5. Vernazza P, Hirschel B, Bernasconi E, Flepp M. Les personnes séropositives ne souffrant d'aucune autre MST et suivant un traitement antirétroviral efficace ne transmettent pas le VIH par voie sexuelle. Bulletin des Médecins Suisses. 2008;89(5):165-169. (PDF in French)
   An unofficial English translation of the statement is available.

6. Cohen M. HIV transmission risk under ART. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract SUSAT4102.

7. HPTN 052: a randomized trial to evaluate the effectiveness of antiretroviral therapy plus HIV primary care versus HIV primary care alone to prevent the sexual transmission of HIV-1 in serodiscordant couples. HIV Prevention Trials Network Web site. Accessed August 5, 2008.

8. Padian NS. Prevention implications. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract SUSAT4107.

9. Dedes N. The view of the civil society. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract SUSAT4103.

10. Hankins C. What are the consequences of the Swiss statement for the rest of the world? In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract SUSAT4105.
    View slides: Download PowerPoint

11. Bongaarts J, Reining P, Way P, Conant F. The relationship between male circumcision and HIV infection in African populations. AIDS. June 1989;3(6):373-378.

12. Moses S, Bradley JE, Nagelkerke NJD, Ronald AR, Ndinya-Achola JO, Plummer FA. Geographical patterns of male circumcision practices in Africa: association with HIV seroprevalence. Int J Epidemiol. September 1990;19(3):693-697.