Half of all recent HIV diagnoses in Brighton gay men identified as recent infections

Half of all new HIV diagnoses in gay men in Brighton involve recent infections, according to a study published in the November edition of AIDS. Brighton has a large population of gay men and investigators combined clinical information with data obtained from enhanced serological testing to determine how many of the men recently diagnosed with HIV had been also recently infected with the virus.

Recent diagnosis or recent infection?

Conventional methods for assessing whether someone newly diagnosed with HIV infection has been recently infected or has been living with undiagnosed HIV for longer than six months are currently imperfect.

Symptoms of seroconversion illness are often generic in nature and can go unnoticed by both doctor and patient. Comparing results with past HIV-negative tests would require an individual to take a test every six months, which is often impractical.

Although a detectable viral load combined with a negative HIV antibody test suggests recent infection, viral load testing is expensive and seldom used in clinics as a diagnostic tool.

And HIV antibody tests, as used in HIV testing clinics, are rarely able to distinguish between chronic and recent infections, although an evolving HIV antibody pattern on serial samples, and/or a Western blot banding pattern limited to four bands, including at least p24 and gp160, can suggest recent infection.

However, several assays that can identify recent HIV infection have been developed for research. These assays – known generically as incidence assays, ‘detuned’ assays, or as the serological testing algorithm for recent HIV seroconversion (STARHS) – have been used primarily on a population level since they are considered to be too unreliable (i.e. suggesting that some recent infections are chronic infections, and vice versa) for individual use. (For more on the various assays and how they work, see this recent aidsmap news story.)

Comparing clinical information with incidence assays

Investigators from Brighton and Sussex University Hospitals and the National Reference Laboratory at the UK’s Health Protection Agency wanted to see whether combining an incidence assay with individual clinical information could more accurately assess recent HIV infection than current methods. Their goal was to more accurately identify the proportion of new diagnoses that were recent infections.

They utilised the Vironostika HIV-1 Microelisa System incidence assay, which measures the intensity of the antibody response and can often detect whether someone has been HIV-infected within the previous five or six months.

The study cohort included 812 (out of a total of 1,526) individuals who presented to the HIV treatment centre at Brighton and Sussex University Hospitals between January 1996 and December 2005, and who had not previously had a positive HIV antibody test elsewhere (i.e. had not simply transferred their HIV clinical care to Brighton).

Of these, 604 (74%) were gay or bisexual men and 208 (26%) were heterosexual (83 male and 125 female), of whom 110 (53%) were known to have acquired their infection in countries of high HIV prevalence. The median ages at diagnosis were 36 years for the gay and bisexual men (range 19 to 82 years) and 34 years for heterosexuals (range 17 to 73 years).

Of the 812 newly-diagnosed individuals, 175 (22%) were initially diagnosed as having recent infection, based on conventional methods. Specifically, 150 individuals had one or more previous negative HIV antibody tests within the previous 18 months; 31 had evolving HIV antibody patterns on serial samples; eight had incomplete western blot assays and one person had a negative HIV antibody test but a positive viral load.

The investigators then tested 1,112 blood specimens (including 397 samples from patients who had moved their care to Brighton, and were definitely chronically infected, plus 715 of the 812 with newly diagnosed infection) utilising the Vironostika incidence assay.

The assay’s results suggested that 289 out of the 1,112 (26%) were recently infected.

The investigators then compared the assay’s results with clinical information obtained from patient notes, including symptoms of seroconversion illness; prior HIV testing history; clinical status at diagnosis; sexual history; other laboratory features suggestive of recent infection; CD4 cell count, viral load and, if available, antiretroviral treatment history.

They assessed that 79 out of the 289 (27%) identified by the assay as being recent infections were incorrect based upon the individual’s clinical history. Consistent with past studies they found that the test identified some individuals with an undetectable viral load, and some with prior AIDS diagnoses, as having recent HIV infection when this was clearly not the case.

The investigators then looked at the 715 individuals who had not previously tested HIV-positive. The incidence assay identified 228 (32%) as having been recently infected. Based on further clinical information, however, 23 (10%) were assessed to have chronic HIV infection: these individuals either had an AIDS diagnosis, low CD4 counts or undetectable viral loads.

They then compared how many more recent HIV infections they had diagnosed with the incidence assay compared to conventional methods of assessing recent infection. They found that 149 out 715 (21%) newly-diagnosed individuals would conventionally have been identified as recent infections, and that the incidence assay identified a further 88 recent infections.

Behavioural and clinical data were available in 73 of these 88: unprotected anal or vaginal intercourse with a partner from a high-risk group within the previous six months was reported by 60 of 73 (82%); and seroconversion illness by 34 of 73 (47%) individuals.

They also found that the incidence test corroborated recent HIV infection in 71 out of 74 (96%) individuals who had a documented HIV-negative test in the previous six months followed by an HIV-positive test. They note, “in the three remaining cases a negative HIV screening test had been recorded between four and five months previously (two subtype B, one unknown)”.

Improving sensitivity

The investigators argue that the assay’s sensitivity (its ability to confirm that recent infections were not chronic ones) was not as poor as it appears at first glance.

Although the assay wrongly identified 79 of 1,112 (7.1%) individuals as having recent infection, they write, “it was only in nine of these 79 (11%) that an obvious cause for the false incident result could not be easily recognised with adjunctive use of clinical or other laboratory data."

"Therefore," they continue, "we found that, when used together, laboratory and clinical data led to a false recent infection rate of only nine of 1,112 (0.8%). Thus our data demonstrate that false incident results can be reliably identified and, conversely, suggest that significant limitations may be associated with surveillance applications if relevant clinical data are not available for individual specimens.”

Conversely, however, the investigators did find that the specificity of the assay (its ability to confirm that chronic infections were not recent ones) was 100%, with 64 of 64 (100%) individuals known to have been diagnosed HIV-positive more than 18 months previously with a CD4 cell count above 200 cells/mm³, viral load greater than 500 copies/ml and not on antiretroviral therapy.

They argue that by combining clinical information with an incidence assay they were able to diagnose a further 88 individuals with recent HIV infection. They believe the benefits of identifying recent infection are many, offering “a unique opportunity to consider early treatment, facilitate partner notification and prevent onward transmission, monitor trends in incidence and resistance, and assess the effectiveness of intervention measures.”

The investigators note, however, that the majority of patients in Brighton are infected with subtype B and that utility of incidence assays in non-B subtypes requires validation before it can be routinely introduced.

Significant increases seen in recent infection in newly-diagnosed gay men

Finally, utilising these methods, the investigators were able to identify significant increases in the proportion of newly-diagnosed gay and bisexual men in Brighton who are being newly-infected with HIV (p < 0.01), whilst HIV incidence in heterosexuals was both low and stable (p > 0.1).

They note that in recent years more than half of all new HIV diagnoses in gay and bisexual men in Brighton were seen in people who were identified as recently infected (50% in 2002; 42% in 2003; 55% in 2004; and 51% in 2005). In contrast, during the same period, fewer than 10% of new HIV diagnoses amongst men and women infected via heterosexual sex were found to be recent infections.

“This demonstrates,” they write, “that ongoing HIV transmission is occurring alongside changing sexual behaviour, despite the awareness of effective HIV prevention strategies and the potential for HAART to reduce the transmission of HIV, and may be an indirect result of the beneficial effects of HAART on HIV-related morbidity and mortality. An alternative explanation is that, particularly among [gay and bisexual men], individuals are presenting more frequently for HIV testing thereby making recognition of recent infection more likely.”