Prevention of HSV-2/HIV-1 Transmission Trial: Research or Death Trap?

By Dr. Givans Kay Ateka, MBChB, MPhil, MPH, DrPH

The article titled “Regional Differences in Prevalence of HIV-1 Discordance in Africa and Enrollment of HIV-1 Discordant Couples into an HIV-1 Prevention Trial”, which appeared in your January 2008 issue reports preliminary results of an ongoing study whose justification should be scrutinized. Although details on the study methodology and end points are scanty, the study objective was to assess the impact of HSV-2 suppression with acyclovir compared to placebo in reducing HIV-1 transmission between discordant couples not eligible for antiretrovirals.

The authors state that prevention trials, which recruit and follow HIV-1 discordant couples, are of particular importance in evaluating interventions for reducing HIV infectiousness while also permitting evaluation of biologic and behavioral factors, which modulate the risk of HIV transmission. Follow up of the enrolled couples is scheduled to run through May 2008; essentially presiding over HIV transmission. There are two ethical issues that this study raises:

1. A basic criterion for research is existence of a significant degree of uncertainty, which a given study aims to settle. That other sexually transmitted infections (particularly ulcerative ones like HSV-2) increase the risk of HIV transmission is a matter of general knowledge. If the researchers undertook the study only to document the magnitude to which HSV-2 suppression reduces the risk of HIV transmission, then this study does not measure up to the ethical principle of beneficence; the obligation to protect persons from harm by maximizing anticipated benefits and minimizing possible risk of harm [1].

2. Although two USA institutions (University of Washington and Emory University) collaborated in the study, no study participants were recruited from the USA. The ethical principle of justice dictates that benefits and burdens of research be distributed equitably. In this case, the stark risk of HIV transmission between discordant couples was wholly shouldered by African study participants.

Though not stated, it could be argued that the study participants provided informed consent and therefore knew the risks they were taking. However, the fact that no study participant was recruited from the USA where people are generally more informed, more aware of their rights and with more options for accessing care suggests that the recruitment was deliberately targeted.

In a paper on factors influencing HIV transmission in Africa [2], I argue that complete lack of or minimal education undermines HIV prevention efforts, which entail discussion of the concept of immunosuppression with people who might not be aware that an immune system exists. Our efforts as researchers, to elicit an informed consent are similarly hampered depending on the complexity of the study in question.

In addition, the prevalent health seeking behavior in most parts of Africa is the expectation of some kind of medication whenever one visits a health facility. For study participants who might not have been on any treatment previously on account of eligibility, the promise of acyclovir or whatever placebo that was used would have been enough to sway them into giving consent in the mistaken belief that they were finally being put on HIV therapy.

It is true that HIV discordance is a public health dilemma [3] but we should not complicate the situation further by facilitating transmission between such couples under the guise of research. With the advent of humanized mice models [4] such studies should take a step back and use the mice models that are likely to provide the relatively academic answers the study seeks without countering the public health core business of prevention. This is a study that should be discontinued on ethical grounds.

REFERENCES

1. The Belmont Report. Ethical Principles and Guidelines for the protection of Human Subjects of Research. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. April 18, 1979.
2. Ateka GK. Factors in HIV/AIDS transmission in sub-Saharan Africa. Bulletin of the World Health Organization. 79(12): 1168, 2001
3. Ateka GK. HIV status disclosure and partner discordance: A Public Health dilemma. Journal of the Royal Institute of Public Health (2006) 120, 493-496. Available online at www.sciencedirect.com
4. Denton PW; Estes JD; Sun Z; Othieno FA; Wei BL; Wege AK; et al. Antiretroviral Pre-exposure Prophylaxis Prevents Vaginal Transmission of HIV-1 in Humanized BLT Mice. PLoS Medicine. January 2008| Volume 5| Issue 1.


The author is the Manager for Enhancing Children’s HIV Outcomes (ECHO) Project in Limpopo Province of South Africa. The opinions expressed in this commentary are his own and do not represent the UK Department for International Development (DFID), which funds his Project.

Contact details:

Dr. Givans Kay Ateka
Provincial Hospital
Department of Pediatrics and Child Health
Private Bag X9316
Polokwane 0700
Republic of South Africa
E-mail: Dr.GivansAteka@kecile.org