HIV treatment and transmission in gay male serodiscordant relationships: The Opposites Attract Study

HIV Australia | Vol. 12 No. 1 | March 2014

By Benjamin Bavinton

BENJAMIN BAVINTON reports on research into ‘treatment as prevention’ among gay male serodiscordant couples.

HIV serodiscordant couples – where one partner is HIV-positive and the other is HIV-negative – are a key context of HIV transmission risk in both heterosexual and gay male populations.

Amongst gay men in Australia, for example, it has been estimated that up to nearly 30% of new HIV infections occur in the context of relationships.¹

While condom use typically tends to be higher in gay male serodiscordant couples than in seroconcordant couples,² it is clear that many gay male serodiscordant couples choose not to use condoms with each other, perhaps using other risk reduction strategies to prevent transmission.

One potential strategy is the use of antiretroviral treatments to prevent transmission.

This strategy of reducing HIV transmission risk by placing the HIV-positive partner on antiretroviral therapy (ART) irrespective of stage of HIV infection has become widely known as ‘treatment as prevention’.³ ⁴ ⁵

Studies in heterosexual HIV serodiscordant couples have provided critical evidence on the role of HIV treatments and undetectable viral load in reducing the risk of HIV transmission.

A number of observational studies, primarily in African heterosexual serodiscordant couples, have demonstrated a link between HIV treatment, undetectable viral load and reduced transmission risk.⁶

In 2011, the early results of a randomised clinical trial, HPTN 052, provided conclusive evidence that when the HIV-positive partner is on ART, transmission risk is dramatically reduced by 96% in heterosexual serodiscordant couples.⁷

We now know that ‘treatment as prevention’ is an effective means of reducing HIV risk for heterosexual serodiscordant couples. However, to date, there is no conclusive evidence on the relationship between ART and transmission in gay male serodiscordant couples.⁸

HPTN 052 did include 37 gay male couples, however there were no linked HIV transmissions within these couples and this number was too small to provide any meaningful evidence on HIV treatment and transmission risk in gay men.

Given that the risk of HIV transmission via anal intercourse is about 10 times greater than for vaginal intercourse,⁹it cannot be assumed that the effectiveness of ‘treatment as prevention’ will be identical for the two types of sex.

As anal intercourse is not uncommon among heterosexuals (for example, 20.9% of adult heterosexual men and 15.1% of adult heterosexual women in Australia report anal sex in their lifetime¹⁰), findings among gay men may also have broader relevance for the effectiveness of ‘treatment as prevention’ in heterosexuals.

While most scientists believe ‘treatment as prevention’ will result in a reduction in risk in gay men, it is not yet clear by how much.

Due to the size of the transmission risk reduction found in HPTN 052, it is likely there will never be another randomised clinical trial of ‘treatment as prevention’, as it would be unethical to place couples into a ‘no treatment’ arm in light of the immense protective effect of treatment.

This means that there is an important role to play by observational studies of HIV treatment and transmission to determine the effectiveness of ‘treatment as prevention’ in gay men.

Globally, there are currently two ongoing studies designed to explore the ‘treatment as prevention’ hypothesis in gay male serodiscordant couples.

First, the Opposites Attract Study is to our knowledge the only research study in the world exclusively examining the association between HIV treatment and HIV transmission within gay male serodiscordant couples.

It is a prospective longitudinal cohort study of such couples, running from early 2012 until the end of 2015.

While originally envisioned to be conducted in 14 Australian clinical sites in Sydney, Melbourne, Brisbane and Cairns, the study will be soon be expanding internationally to new sites in Brazil and Thailand.

The couples attend a participating clinic at least twice per year for blood tests and STI tests, and complete a detailed questionnaire after each clinic visit.

In cases of seroconversion in the initially HIV-negative partner, phylogenetic analysis will be used to determine whether the transmission was within the couple, or whether it was from an outside partner.

Additionally, for couples participating in Sydney, Bangkok and Rio de Janeiro, HIV-positive partners can also elect to join a sub-study looking at HIV viral load in semen.

Couples are eligible to participate if one partner is HIV-positive, the other partner HIV-negative, they have regular anal sex with each other, and still expect to be having sex with each other in three to six months’ time.

Previous research has demonstrated that HIV transmission is more likely in the early stages of relationships.¹¹

Consequently, the eligibility criteria were designed to ensure that couples in very new relationships – and indeed, sexual partners who do not consider themselves to be in relationships at all – are welcome to participate.

HIV-positive partners in the couples can be currently taking ART, not taking ART, or can start taking it at any point during the study.

Furthermore, the study is open to couples who always, sometimes or never use condoms when having anal sex with each other.

The second study of ‘treatment as prevention’ internationally is PARTNER (‘Partners of people on ART – a New Evaluation of the Risks’), which is being conducted in 72 clinics across the UK and Europe.¹²

PARTNER is open to both heterosexual and gay male serodiscordant couples and explores the absolute level of HIV transmission risk in serodiscordant couples where the HIV-positive partner is on ART and has undetectable viral load, in the absence of condom use.

It is also an observational cohort study where couples are followed up over time, and will also utilise phylogenetic analysis to determine if HIV transmissions are from within the couple or from outside partners.

The PARTNER Study focuses on measuring the HIV incidence in both heterosexual and homosexual serodiscordant couples having unprotected anal and/or vaginal intercourse, and is restricted to couples where the HIV-positive partner is receiving ART and has undetectable viral load at enrolment.

By contrast, Opposites Attract will allow the calculation of HIV incidence in couples where HIV-positive partners are on ART or not on ART, and with undetectable versus detectable viral load (and semen viral load in a subsample of couples).

Furthermore, the detailed behavioural and attitudinal data from the participant questionnaires will allow exploration of many contextual factors associated with HIV risk, behavioural risk compensation, and the negotiation of sexual practice within couples.

As governments and communities world-wide move forward with HIV prevention strategies incorporating ‘treatment as prevention’, it is critical that studies on HIV treatment and transmission specifically within gay male serodiscordant couples form part of the evidence-base guiding the response.

Opposites Attract is recruiting now. For more information on the Opposites Attract Study, please visit www.OppositesAttract.net.au

References

1 Volk, J., Prestage, G., Jin, F., Kaldor, J., Ellard, J., Kippax, S., et al. (2006). Risk factors for HIV seroconversion in homosexual men in Australia. Sexual Health, 3(1), 45–51.

2 Hull, P., Mao, L., Kao, S., Edwards, B., Prestage, G., Zablotska, I., et al. (2013). Gay Community Periodic Survey. National Centre in HIV Social Research (NCHSR), University of New South Wales, Sydney.

3 Montaner, J. (2011). Treatment as prevention—a double hat-trick. The Lancet, 378(9787), 208–209.

4 Smith, K., Powers, K., Kashuba, C., Cohena, M. (2011). HIV-1 treatment as prevention: the good, the bad, and the challenges. Current Opinion in HIV and AIDS, 6(4), 315.

5 Hammer, S. (2011). Antiretroviral treatment as prevention. New England Journal of Medicine. doi: 10.1056/NEJMe1107487

6 Attia, S., Egger, M., Müller, M., Zwahlen, M., Low, N. (2009). Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS, 23(11), 1397.

7 Cohen, M., Chen, Y., McCauley, M., Gamble, T., Hosseinipour, M., Kumarasamy, N., et al. (2011). Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine.

8 Muessig, K., Smith, M., Powers, K., Lo, Y-R., Burns, D., Grulich, A., et al. (2012). Does ART prevent HIV transmission among MSM? AIDS, 26(18), 2267.

9 Vittinghoff, E., Douglas, J., Judon, F., McKiman, D., MacQueen, K., Buchinder, S. (1999). Per-contact risk of Human Immunodificiency Virus tramnsmision between male sexual partners. American Journal of Epidemiology, 150(3), 306.

10 Visser, R., Smith, A., Rissel, C., Richters, J., Grulich A. (2003). Sex in Australia: heterosexual experience and recent heterosexual encounters among a representative sample of adults. Australian and New Zealand Journal of Public Health. 27(2), 146–154.

11 Bavinton, B., et al. (2012, 17 April). Exploring gay men’s serodiscordant relationships: Implications for future ‘treatment as prevention’ studies in gay men. Presentation delivered at M2012: International Microbicides Conference, Convention and Exhibition Centre, Sydney.

12 Rodger, A., Bruun, T., Weait, M., Vernazza, P., Collins, S., Estrada, V. (2012). Partners of people on ART – A New Evaluation of the Risks (The PARTNER study): design and methods. BMC Public Health. 12(1), 1–6.

Benjamin Bavinton is Project Leader for The Opposites Attract Study and Associate Lecturer at the Kirby Institute.