Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
In which countries is HIV most prevalent?
The epicentre of the HIV pandemic is in sub-Saharan Africa, though prevalence of infection varies dramatically between countries for reasons not completely understood.
According to UNAIDS estimates, the four countries with the most severe epidemics are Botswana, Lesotho, South Africa, and Swaziland. In these countries, HIV prevalence ranges from 13-21% and 23-30% in adult males and females, respectively.
Until recently, we have had surprisingly poor estimates of country-wide HIV prevalence. For a long time, all country estimates of HIV prevalence were based on anonymous testing of pregnant woman at antenatal clinics. This has been the best available data, but sexually active women are hardly a representative sample of the whole population.
Only with the start of more representative surveys that included HIV testing in the mid 2000’s (such as the Demographic and Health Surveys that we analysed) did we really begin to understand exactly how severe the epidemics were.
Please can you explain how your research into HIV and extra-couple relationships originated?
Along with two of the co-authors (Jonathan Dushoff and Brian Williams) and several other colleagues, I teach an annual two-week workshop on mathematical modelling of infectious diseases at the African Institute for Mathematical Sciences outside of Cape Town, South Africa. Part of the workshop involves participants and faculty working together on group projects.
In 2011, Brian proposed applying a previously published analysis—that assessed how much HIV transmission in couples came from inside versus outside their relationships—to new data for a group project. This project seemed to have huge potential, but it became apparent that there were some major flaws with the original analysis.
After the workshop, the analysis was put on hold for half a year simply because it didn’t seem possible to do it well. I was also busy finishing up my PhD at the University of California, Berkeley. Until this project my research had been mainly focused on investigating anthrax outbreaks in zebra in a Namibian national park so this project seemed like a potentially unfruitful distraction.
Finally, largely because of the persistence of Kathryn Fiorella (a workshop participant and also a co-author) in pushing for the continuation of this project, I spent a week on this project last February to see if we could rescue it. Once we realized that we could use data on how long individuals were sexually active before entering relationships to fix the problems with the original analysis, things happened very quickly. I took a break from my other research and started working on this full-time.
What did your research involve?
We analysed Demographic and Health Survey data acquired from interviews and HIV tests of 27,000 stable, cohabiting couples from across 18 African countries. We wanted to figure out what proportion of infected individuals were infected before even entering their current relationship, by their current partner, or by extra-couple intercourse (i.e., sex with someone outside the relationship but while there with their current partner).
The key to our approach was to use data that we could be reasonably sure was accurate (i.e., rather than self-reported behavioural data on infidelity). The only survey data we used was when each member of a couple first became sexually active, when they entered their current relationship, and their HIV test results.
These data were enough to help us estimate the probability that HIV-positive partners were infected before or during their current relationship in three different ways. First, infected partners who reported not having been sexually active before their current relationship must have been infected during their current relationship.
Second, HIV-positive partners in couples formed early on in the HIV epidemic are very likely to have been infected during their current relationship because there were so few individuals to infect them beforehand.
Third, because untreated HIV-infected individuals generally do not survive much beyond about 10 years after being infected, all observed HIV-positive individuals were likely to have been infected in the past 10 years (most of the couples analysed did not have access to life-prolonging antiretroviral treatment until very recently). So infected partners in couples formed more than about decade ago were likely to have been infected during their current relationship.
For infected individuals whose partners are HIV-negative (i.e., so-called serodiscordant couples), knowing whether an individual was infected during their current relationship is the same as knowing whether he or she was infected by an extra-couple intercourse, because such individuals could not have been infected by their partners (who are uninfected).
By formalizing these ideas into a mathematical model, we were able to estimate the overall proportion of observed infections that were due to transmission before individuals’ current relationships, by their partners, or from extra-couple intercourse.
What did your research find?
We found that extra-couple transmission has been and continues to be a relatively common contributor to new HIV infections. We estimate that, of new HIV infections in 2011 within stable, cohabiting couples, 30-65% and 10-47% (depending on the country) were due to extra-couple transmission in men and women, respectively.
We also found that within couples transmission occurs more from man to woman than vice versa, although both directions are frequent. Finally, we confirmed the conclusions of other studies that women appear to be at exceptionally high risk to infection whilst single before their first stable, cohabiting relationship.
What impact do you think your research will have?
HIV/AIDS policy is currently at a crossroads. There have been several exciting developments in the past two years. Most notably, we now know that antiretroviral treatment, by reducing the amount of virus circulating within HIV-positive individuals, also dramatically reduces how infectious they are to their sexual partners. This means that we can use treatment not only to keep infected individuals healthy, but also to prevent new infections.
The logical conclusion is that infected individuals should start receiving treatment early, even before they get sick or their immune system begins to fail. Consequently, the World Health Organization issued new guidelines last April recommending that HIV-positive individuals with known HIV-negative partners should be given treatment immediately instead of waiting until they become sick or show signs of being immunocompromised.
This is a commendable major step forward. Further, a new strategy of offering couples the opportunity to test, receive their results and mutually disclose their status in a supportive counseling environment will be key to the success of couples-based treatment as prevention.
However, our research points out that a large proportion of transmission does not occur between the members of stable, serodiscordant couples. A lot of infections occur while individuals are single or from extra-couple intercourse. This means that infected individuals should be given early treatment regardless of whether they are in a stable relationship with an uninfected individual.
Even though their sexual partners are not easily identifiable and have not been tested with them, they are still at risk. Thus, while serodiscordant couples are a good and relatively easily targeted sub-group to target at first, we propose expanding treatment as prevention.
We are by no means the first to propose the idea of putting all infected individuals on treatment immediately. The concept, known as ‘test and treat’, has received quite a lot of consideration in recent years and there are several large intervention trials being designed to see how it works. Our research suggests that it is likely to have a much greater effect on curbing the epidemic than the current more limited focus on stable, serodiscordant couples.
Why do you think transmission in couples occurs more from men to women than vice versa?
Firstly, this directional trend is only very slight. We found that women also infect their male partners quite often too.
Many factors determine who infects whom. Men tend to have been sexually active for much longer than women before they enter a stable relationship, and thus have more time to accumulate infection risk.
However, the fact that women are only sexually active for much shorter periods before entering a relationship is largely compensated by a much higher risk of infection during this time (potentially because they are having intercourse with older men who have a higher HIV prevalence) compared to men.
Men also appear to have a slightly higher extra-couple transmission rate, which we suspect is due to behavioural differences. These two reasons make men more likely to introduce the infection into a couple first.
How do you think the future of HIV epidemics will develop?
I think we are all optimistic now that we now know that treatment can not only prolong lives, but also prevent new infections. The future lies in the details, however.
Not everyone who should be on antiretroviral treatment under current guidelines is receiving it, so ramping up treatment to everyone who is infected at countrywide or continental scales is no small task. This will take a lot of sustained commitment of funding and other resources, logistical savvy, as well as careful monitoring of drug resistance.
We will know a lot more in the coming years once the results of planned communitywide intervention trials are available.
Do you have any plans for further research into this field?
Yes, very much so. This is a very important field and things are changing very quickly right now so there are a lot of open questions that policymakers need answered.
Where can readers find more information?
About Steve Bellan
Dr. Steve Bellan is a postdoctoral researcher at the Center for Computational Biology and Bioinformatics at the University of Texas at Austin.
Originally trained as an ecologist and applied mathematician, he began his interest in infectious disease epidemiology while completing his PhD at the University of California at Berkeley. His PhD research focused primarily on better understanding the causes and consequences of anthrax, rabies, and canine distemper outbreaks in the herbivores and carnivores of Etosha National Park, Namibia.
His research now spans multiple infectious diseases in humans and animals, but is united under an overarching theme: the integration of mathematical and statistical models with empirical data to better understand infectious disease processes and how to control them.
For more information on Steve, please visit: http://www.bio.utexas.edu/research/meyers/steve_bellan/