Phylogenetic analysis of the source of HIV infections in Dutch gay men over more than a decade shows that 71% acquired HIV from a man who was himself not yet diagnosed and only 6% from a man who was taking treatment, Oliver Ratmann and colleagues report in this week’s issue of Science Translational Medicine.
Examining what could have been different if prevention activities were scaled up, the researchers estimate that a combination of annual HIV testing, PrEP for half of all HIV-negative gay men and immediate HIV treatment for those testing positive could have averted two thirds of these transmissions. They say the results highlight the importance of combining the interventions – singular approaches would have much less impact.
Understanding which interventions could make a difference to the Dutch gay epidemic is an important case study, they say. The substantial scale-up of HIV treatment there has not stemmed new HIV infections. Although 90% of diagnosed men are on treatment, 91% of those on treatment are undetectable and 95% of diagnosed men are retained in care, HIV incidence is stable or increasing. Other developed countries, including the UK, have a similar problem.
Sources of HIV transmission
The researchers analysed the genetic characteristics of stored blood samples obtained from Dutch patients living with HIV. Using a technique called phylogenetic analysis, they looked for infections with similar genetic profiles which were likely to constitute transmission events.
They first identified gay men who were diagnosed with HIV between 1996 and 2010 who probably acquired HIV less than a year before their diagnosis. They then attempted to pair their blood samples with those of other men who had HIV at the time the transmission is likely to have occurred and who may have been responsible for it. This entailed looking at blood samples of men who were already diagnosed at the time and also of men who were only diagnosed (and provided a blood sample) some years later. Since most people living with HIV in the Netherlands have samples in the database analysed, a significant proportion of transmission pairs could be identified.
Of 1045 recently diagnosed gay men who had a blood sample available for analysis, 617 could be paired with one or more probable transmitters. In total there were 903 probable transmitters and 2343 pairs. The researchers determined whether a probable transmitter was diagnosed and taking treatment at the time of suspected transmission.
This showed that:
- 71% of transmissions originated in undiagnosed men
- 22% originated in men who were diagnosed and not yet taking treatment
- 6% originated in men were taking treatment
- 1% originated in men who had dropped out of medical care.
Moreover, 43% of those transmitting HIV had themselves only had it for less than a year.
The researchers note the very limited number of transmitters who were taking HIV treatment, confirming that treatment is highly effective in preventing transmission. Similarly, only 1% of transmissions came from men who were lost to follow-up.
“The lack of substantial reductions in incidence among Dutch MSM is not a result of ineffective ART provision or inadequate retention in care,” they comment.
While a fifth of transmissions did come from diagnosed men who were not yet on treatment, this is a historical sample (up to 2010) and HIV treatment has been scaled up since then. It is likely that data for more recent years would show fewer transmissions from this group.
The researchers then modelled the proportions of transmissions that could have been avoided if various health interventions had been available. They looked specifically at the period 2008 to 2010, considering these possible interventions:
- Immediate HIV treatment for all men diagnosed with HIV
- PrEP for half the HIV-negative gay men aged under 30
- Annual HIV testing for half the gay men who transmit HIV.
The researchers comment on the difficulty of achieving high rates of HIV testing in those most likely to be involved in transmission. Their data suggest that these men test less frequently than other gay men, but it is not clear how health services can reach these individuals or identify them.
If only immediate treatment had been offered, 19% of infections could have been averted. Combining immediate treatment and PrEP would have prevented 30% of infections. The greatest results would be seen by combining these with annual testing, averting 45% of infections.
Expanding PrEP access to half of all gay men (rather than just those under the age of 30) would prevent 66% of infections.
“This study indicates that substantial reductions in HIV incidence among MSM could have been realized with a combination approach that includes – critically – increased annual testing, with uptake of PrEP by young MSM testing negative and provision of immediate ART to those testing positive,” the authors say.
They believe that the most important implications for prevention programmes are for a scale-up of HIV testing and of PrEP. As coverage of HIV treatment has already been considerably expanded since the period of study, there is limited potential in making further changes to treatment guidelines. The focus must therefore be on intensifying prevention interventions for HIV-negative people.
“Increased annual testing and uptake of PrEP by men at high risk of infection have a key role to send the HIV epidemic among MSM into a decisive decline,” they conclude.
Ratmann O et al. Sources of HIV infection among men having sex with men and implications for prevention. Science Translational Medicine 8: 320ra2, 2016. (Abstract).