People with HIV outside continuous care contribute disproportionately to viral load and infection potential, Canadian study finds

A study from Calgary in Canada has found that people who were in continuous care for a year, although representing nearly 80% of all people with diagnosed HIV, contributed less than 30% of the total viral load within the diagnosed HIV-positive community.

It found that while people who were newly diagnosed accounted for 37.5% of the total viral load, the other 33% was accounted for by a mix of people arriving from other areas, returning to care after an absence, moving away or being lost to care.

What the researchers in this study call ‘churn’ – a term used to mean patient movement in or out of a community – may therefore be contributing about a third of the total infection potential within that community, if conditions are similar to those in Calgary.

Given that absence from and loss to care are potentially modifiable, efforts to ensure that people living with HIV stay in care could form a significant part of efforts to use HIV therapy to reduce HIV incidence (so-called 'treatment as prevention' or TasP).

Background

One of the most frustrating modern problems in HIV prevention is that while successful HIV treatment that reduces a person’s HIV viral load to undetectability appears drastically to reduce the likelihood of their passing HIV on to others as individuals, this does not always translate into falls in the rate of new HIV infections (incidence) in the community. 

The UK is one example of a country where, despite the fact that HIV testing rates are improving and a majority of people with HIV are thought to be on antiretroviral therapy (ART) with undetectable viral loads, HIV infections in gay men and heterosexual people show no signs of declining.

Some epidemiologists have suggested that the majority of new infections within communities come from people who are undiagnosed; estimates of the proportion of HIV passed on by people who have themselves recently acquired HIV range from less than 10% to about 50%.

These have led to calls for regular HIV testing and referral to care to be given a high priority as the aim of HIV prevention campaigns. 

Getting people diagnosed may not be the only crucial step in what has been called the ‘HIV care cascade’. Supporting people to stay in care and on ART may be just as crucial.

This may particularly apply to countries without centralised healthcare systems such as the US, where the Centers for Disease Control estimate that less than 30% of the HIV-positive population is on ART with an undetectable viral load. 

It has been assumed that this is due to socioeconomic inequalities and high numbers of people with HIV in the US not having health insurance, and therefore being unable to access regular care. More recent US studies presented at this year’s Conference on Retroviruses and Opportunistic Infections (CROI), however, suggest that high levels of patient mobility, or too-strict definitions of what constitutes viral suppression, could be leading to overestimates of how many people are not in regular care.

The study

The Canadian study is the first to try to quantify viral load not only in the recently diagnosed and people in regular care, but also in people who leave or return to care.

It finds that while the newly diagnosed form a significant proportion of those likely to pass on HIV, people moving into or out of care also contribute a high proportion.

The study had a couple of advantages over US models. Firstly, being Canadian, it was able to study viral loads in people in a centralised and free healthcare system. Secondly, HIV care in Canada is generally provided by large specialist clinics and the clinic in Calgary is isolated, with the next one being 180 miles north in Edmonton. It was thus able to study people moving in and out of a relatively defined population.

Results

The researchers first looked at general diagnosis and viral load trends between 2001 and 2011. The total number of people in HIV care in Calgary doubled in this time, from 757 to 1423. The proportion on ART increased from 62 to 81%, and the proportion with viral loads under 50 copies/ml doubled from 32 to 66%.

However, the rate of new diagnoses increased from 4.4 to 5.8% a year and the mean viral load per patient in care did not significantly change: it was 32,000 copies/ml in 2001 and 30,000 copies/ml in 2010.   

At first sight this seems a paradoxical result: how can the average viral load stay the same while the proportion who are undetectable doubles? The answer is that as the proportion in regular care who are virally suppressed increases, so the people who are not virally suppressed are ever more likely to be those who are newly diagnosed or not in regular care.

To examine exactly which people have detectable viral loads, the researchers took a closer look at everyone seen for care in 2009 at the Calgary clinic and split them into six groups. In all groups, average viral load was the mean of all viral load tests taken during 2009; people with an undetectable viral load were treated as having viral loads of 50 copies/ml exactly, so someone with several viral load tests would have to be undetectable in all of them to be classed as having a mean viral load of 50 copies/ml during 2009.

       1.    People in continuous care through the year. These formed 78.7% of patients. Sixty-eight per cent had viral load under 50 copies/ml and the mean viral load in this group was 10,500 copies/ml. When the viral loads of everyone in this group were added together, they carried only 29.5% of the total community viral load in the clinic’s patients.  

       2.    Newly diagnosed people. These formed only 6.6% of patients. However, because the mean viral load in this group was 162,000 copies/ml, the proportion of the total viral load carried by these patients was 37.5%. Viral loads in undiagnosed people within the community are likely to be similar.

 Between them, these two groups carried two-thirds of the total viral load burden, so to speak, of the community. The other third was carried by four groups who also, without exception, had higher mean viral loads than those in continuous care.· 

       3.    New arrivals. These are people who had been diagnosed elsewhere but had moved to Calgary. They formed 4.8% of all patients but had a slightly higher mean viral load than those in care and were only half as likely to have viral loads under 50 copies/ml as people in care in Calgary all year.

       4.    Returners. These were people who had dropped out of care in Calgary but had then returned some time later. Although they only formed 4.2% of people seen for care in 2009, they carried 16.6% of the total viral load burden: this was because their mean viral load was almost as high as the newly diagnosed, at 107,000 copies/ml. Three-quarters of this group had been lost to follow-up and, of these, over 80% said they stayed in Calgary but did not attend medical care.

       5.    Leavers. These are people who moved out of the area to another known clinic. These formed 2.6% of patients and only carried 2.4% of the total viral load burden. Even so, only 43% had viral loads under 50 copies/ml throughout the year compared with 68% in continuous care; their mean viral load was 25,000 copies/ml.

       6.    Lost to care. These were people who stopped attending care ('lost to follow-up'). Although they only formed 3.1% of all patients they carried 8.5% of the total viral load burden and their mean viral load was 73,000 copies/ml.      

What this means is that in total the 15% of patients who were neither in continuous care nor newly diagnosed shared between them 33% of the total viral load of people who attended care in 2009. Furthermore, while only 19% of those in continuous care had viral loads over 200 copies/ml (which was regarded by the researchers as the criterion for viral ‘suppression’), 68% of those in discontinuous care did, and 82% of those who were either lost to follow-up (at their last viral load test) or who returned from being lost to follow-up.

Conclusions

On the one hand, as the researchers point out, this means that simply looking at the proportion of people who have suppressed viral load in continuous care may bear no relation to the proportion suppressed in the community at large, even if the proportion who are undiagnosed is estimated with reasonable accuracy. It also shows that people in discontinuous care, particularly those lost to follow-up, may form nearly as large a part of the pool of people who have a high risk of passing on HIV to others (infectiousness) as those who are undiagnosed do.

On the other hand, it also means that, since the proportion of people lost to follow-up can be reduced, and people can be brought back into care, by more intensive tracing and follow-up methods, this potentially infectious pool can be reduced.

There is one caveat from this study: as a group of researchers have recently remarked, “community viral load” in itself is not necessarily an accurate guide to the ongoing likelihood of infection in populations. This is because other factors may affect incidence such as socioeconomic disadvantage, behaviour change, demographic changes, the distribution of risk behaviour within members of the HIV-positive community and the overall prevalence of HIV within the local population – including among the undiagnosed.

It does however give a general guide as to the relative proportion of people within the community who are not virally suppressed and who therefore may be capable of infecting others.