Denmark shows first clear evidence of the success of treatment as prevention in gay men in a high income country

A study by the University of California, Los Angeles, and Copenhagen University Hospital provides the first unambiguous evidence of a link between high rates of viral suppression in gay men and falling HIV incidence (the proportion of men who catch HIV each year).

The researchers say that HIV incidence among gay men, at a rate of 0.14% a year or one in 700 gay men infected annually, is now so low that it approaches the one per 1000 annual incidence rate that the World Health Organization has set as the threshold for eventually eliminating the HIV epidemic.

They estimate that the percentage of gay men and other men who have sex with men (MSM) in Denmark who have HIV and an undetectable viral load on treatment is now 72.1% – very close to the 72.9% that UNAIDS’ 90/90/90 target sets for ending the HIV epidemic.

Denmark’s HIV epidemic has long been concentrated in MSM and in particular has had very low HIV prevalence in people who inject drugs due to harm reduction programmes being available for decades. Reducing HIV in MSM would therefore reduce it in the whole country.

The researchers find that the reduction in HIV incidence was not driven by changes in the CD4 count threshold for starting treatment, as it started falling before guidelines were changed. Instead, increased rates of testing drew more people into medical care directly and so they were diagnosed earlier, at higher CD4 cell counts.

They also find that despite the falling incidence, the transmission rate – the number of people infected on average by each virally unsuppressed man – almost doubled during the period of the study. They comment that this is probably due to increased risk behaviour, but that increasing the number of people on antiretroviral therapy (ART) has nonetheless more than compensated for this. They add, however, that it will be essential to use other interventions with proven efficacy such as pre-exposure prophylaxis (PrEP) in order to reduce transmission and infection rates among the undiagnosed and those at high risk of HIV.

Results in detail

Denmark has had a national HIV database since 1995 that includes every person diagnosed with HIV in the country, and a national cohort study that included the majority of those diagnosed since 1991.

This records that the number of new HIV diagnoses per year in MSM fell from 152 in 1991 to 68 in 2000. It then rose again to a peak of 139 in 2007.

Since then, however, it has declined again, to 76 diagnoses in 2013 - and only 58 in the previous year, 2012.

Denmark instituted ART rapidly and nearly three-quarters of its diagnosed MSM were on ART by 1998; more than 50% of diagnosed MSM had achieved undetectable viral loads by 2001.

Increased testing led to a rapid fall in the proportion of MSM diagnosed with CD4 counts below 200 cells/mm³, from about 40% before 2000 to less than 20% after 2003. The proportion diagnosed with CD4 counts over 500 cells/mm³ increased alongside this, though slightly more gradually, from about 20% pre-2000 to about 40% post-2005.

2002 was the crucial year after which more MSM were diagnosed with high rather than low CD4 counts and this coincides with a sudden jump in the average CD4 count on diagnosis from roughly 230 cells/mm³ before then to roughly 400 cells/mm³ since then (it was 560 cells/mm³ in 2012).

Taking as a denominator an estimate of the MSM population in Denmark of 55,000, the researchers estimated that the number of MSM with HIV who are undiagnosed fell from about 1400 in 1995 to only just over 600 in 2013, and the number with CD4 counts below 200 cells/mm³ from 190 to only 40.

The researcher calculated that the number of gay men in the population who, during the course of any one year, are HIV-positive and are not completely virally suppressed and therefore infectious, has declined from just over 2200 in 1996 to just over 800 now. In 1996 half of these potential transmitters were diagnosed, but either not on treatment or on failing treatment. In 2013 only a third (about 230 men) are in that category and a tiny number – only about 35 men – were on failing ART.

The figures given so far refer to annual diagnoses rather than true incidence; other factors such as increases in testing rates also influence diagnoses. However by making a rough estimate (back-calculation) of the time since infection, based on the average CD4 count at diagnosis, the researchers were able to calculate that the absolute number of MSM infected in Denmark per year declined from 117 in 1994 to 70 in 2013 (the number diagnosed that year was 76).

The researchers noticed at least one threshold effect. They note that incidence only started decreasing when the proportion of all HIV-positive MSM on treatment (including the undiagnosed) rose to more than 35%.

One important finding is that though incidence fell, it did not fall by as much as diagnoses. And the transmission rate – the number of times each virally unsuppressed MSM transmits HIV – rose. In 1996, the researchers calculated, just over five in every 100 virally-unsuppressed MSM transmitted HIV to another partner each year. By 2012 this had nearly doubled to nine in every 100 per year. This is probably due to increased levels of risk behaviour, and also a concentration of that risk behaviour into a shrinking pool of high-incidence gay men.

Implications

This may be the explanation for another threshold the researchers show in a graph but do not refer to. Incidence stayed flat at 80 infections a year once the proportion on treatment rose above 55%. It then started to decrease further when the proportion rose above 70%. We have noted already that diagnoses increased temporarily between 2000 and 2007 before falling again. This could show that a greater proportion of people in a population with a high level of HIV risk behaviour and biological vulnerability needs to be virally suppressed before incidence starts falling than in a population with lower levels of risk behaviour.

This could explain why, in KwaZulu Natal, in one of the few other studies to show a direct correlation between the proportion of people virally suppressed and HIV incidence, incidence started falling when treatment coverage reached 30%, but that incidence is still increasing in countries like the UK that have the same viral suppression rates as Denmark. Some researchers have calculated that it could take viral suppression rates of as high as 90% to started bringing incidence down in the UK, in the absence of PrEP or positive behaviour change.

The researchers stress that this has only been achievable in Denmark because “notably, there is universal access to health care in Denmark, with free HIV treatment and many easily-accessible walk-in clinics that provide HIV testing and linkage to care.”