Research focus: spotlight on a recent publication involving SHM data

Daniela Bezemer.jpgDaniela Bezemer is an evolutionary epidemiologist working at Stichting HIV Monitoring. Recent work resulting from a long-standing collaboration with the infectious disease modelling group of Christophe Fraser at Imperial College London, and Anne Cori in particular, on HIV transmission among men who have sex with men (MSM) in the Netherlands has just been published in PLOS Medicine. Building on previous work in which they found that there was a resurgent HIV-1 subtype B epidemic among MSM in the Netherlands, they now sought to identify whether this resurgent epidemic was due to newly-introduced strains or already circulating strains. To this end, they performed a combined phylogenetic and mathematical analysis using HIV sequence data. These data are collected for many patients to screen for resistance mutations and thereby ensure optimal combination therapy. Here, Daniela describes the highlights of the paper and what her plans are for future research.

Could you briefly summarise the main findings of your paper?

The study provides insight into the different sub-epidemics  that have contributed to the ongoing resurgent HIV epidemic amongst MSM in the Netherlands. We found that several sub-epidemics that started spreading before the introduction of cART in 1996 still constitute the main source for new HIV-1 subtype B infections. When we calculated the reproduction number (average number of new infections per infection) separately for each sub-epidemic, we found that, although the epidemic diminished at the population level during the 1990s, most of these sub-epidemics continued spreading. There is little indication that any of the sub-epidemics will stop in the near future, as these are shifting towards new generations of MSM, and continue despite many MSM being diagnosed early in infection.

Conceptually it is interesting to see the whole HIV-1 subtype B epidemic disaggregated in a single figure. For example, this illustrated the tight links between clusters on Curaçao and people from the same region living in the Netherlands. It also showed that the largest transmission cluster, which is dominated by people who injected drugs, has links to heterosexual transmission, but is an almost entirely separate epidemic from that seen amongst MSM.

What is new about your study?

We found that the resurgent epidemic is the result of several sub-epidemics, many of which started since the early epidemic, and to which new sub-epidemics are being added. There seems to be a high and continued rate of infections introduced from abroad, but with only a small minority of these going on to establish new epidemics. This is in line with expectations from epidemiological theory: self-sustaining sub-epidemics are hard to establish, but, once initiated, are difficult to stop. This study, combining phylogenetic methods with mathematical modeling to analyse extensive HIV-1 subtype B sequence data, helps to understand how different sub-epidemics together contribute to the resurgent HIV epidemic in the Netherlands. The analysis suggests that the epidemic amongst MSM is dispersed amongst a large number of sub-epidemics, many of which persisted throughout the 1990s, before increases in risk behaviour became widespread.

What are your plans for future research?

We have started an analysis that should provide insight into the level of transmission of the non-B subtypes in the Netherlands. Non-B infections are largely found among heterosexuals from Sub-Saharan Africa, but we also found sub-clusters amongst MSM with Dutch origin. The more difficult question that we would like to answer is to what extent heterosexuals with Sub-Saharan African origin become infected within the Netherlands.

Bezemer D, Cori A, Ratmann O, van Sighem A, Hermanides HS, Dutilh BE et al. (2015). Dispersion of the HIV-1 epidemic in men who have sex with men in the Netherlands: A combined mathematical model and phylogenetic analysis. PLoS Med 12 (11):e1001898.doi10.1371/journal.pmed.1001898