Denmark: Late HIV diagnosis not a major factor in continued spread of HIV

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Individuals whose HIV infection is diagnosed late are making only a minimal contribution to the HIV epidemic, Danish investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Using phylogenetic anaylsis, researchers were able to trace transmission clusters. Only 20% of people diagnosed late were located within such a cluster.

However, the study’s findings provide further evidence that people who have only recently been infected with HIV are largely sustaining the spread of HIV. Almost all the transmission clusters identified by the investigators involved young gay men, many of whom had primary HIV infection.

HIV incidence has been stable in Denmark over the past 20 years. There are approximately 300 new infections each year in the country. Several studies have now shown that the majority of onward HIV transmissions originate in individuals with undiagnosed infection. However, the contribution of individuals whose HIV is diagnosed late (with a CD4 cell count below 200 cells/mm3) is currently unknown.


transmission cluster

By comparing the genetic sequence of the virus in different individuals, scientists can identify viruses that are closely related. A transmission cluster is a group of people who have similar strains of the virus, which suggests (but does not prove) HIV transmission between those individuals.


A person who has never taken treatment for a condition.

primary infection

In HIV, usually defined as the first six months of infection.


In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

phylogenetic analysis

The comparison of the genetic sequence of the virus in different individuals in order to determine the likelihood that two or more samples are related. This involves creating a hypothetical diagram (known as a phylogenetic tree) that estimates how closely related the samples of HIV taken from different individuals are. Phylogenetic analysis is not a reliable way to prove that one individual has infected another, but may identify transmission clusters, which can be useful for public health interventions.

Investigators therefore conducted a study involving the 1515 people newly diagnosed with HIV in Denmark after 2001. Using a technique called phylogenetic analysis, the authors looked at networks and clusters of HIV transmissions to see if they could identify the factors that are driving the HIV epidemic in the country.

Approximately a fifth (260) of people were found to have primary HIV infection and 460 individuals were diagnosed late. A total of 696 infections involved gay men.

The investigators identified a total of 46 transmission clusters involving 502 people.

“We found one third of the sequences from newly diagnosed, treatment naïve patients formed 46 different phylogenetic clusters visualising potential local epidemics,” comment the authors.

People within transmission clusters had a significantly higher CD4 cell count (402 vs 287 cells/mm3, p < 0.001) and higher viral loads (63,000 vs 25,000 copies/ml, p < 0.05) than individuals who could not be placed within transmission networks.

Half of all people with primary HIV infection could be placed within a cluster, compared to only 22% of people whose HIV was diagnosed late.

“Individuals presenting with low CD4 T-cell counts contribute less to the epidemic than individuals with higher CD4 T-cell counts,” observe the researchers.

Age under 30, injecting drug use, primary infection and sex between men were all significantly associated with being in a cluster (p < 0.001).

Some 40 clusters involved gay men, and the two largest transmission networks involved half of all people with primary infection.

“Within 46 clusters we found primary HIV sequences more frequently in larger clusters,” comment the investigators. They believe this is “compatible with the increased infectiousness and transmission potential….ascribed to primary HIV infection”.

Several of the clusters spanned the full study period, “an explanation for the constant level of HIV diagnoses in Denmark”.

The study’s findings have implications for HIV prevention. The authors recommend that efforts should be targeted at younger gay men, especially those at risk of having primary infection. “Very late presenters do not seem to be of significant importance from the transmission standpoint. Efforts to identify very late presenters should be enhanced for the benefit of the individual patient.”


Audelin AM et al. Phylogenetics of the Danish HIV epidemic: the role of very late presenters in sustaining the epidemic. J Acquir Immune Defic Syndr, online edition, DOI: 10.1097/QAI.0b013e318276becc, 2012.