Seven simple questions about symptoms and risk factors identified three-quarters of gay men in Amsterdam who have acute (very recent) HIV infection, according to a study presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle last month. Using this risk score could identify gay men requiring HIV RNA testing (which can detect acute infections) in addition to HIV antibody testing.
Promptly diagnosing people who have acute HIV infection is important from both an individual and a public health perspective. But, diagnosis is challenging because the symptoms of acute infection can be caused by other common health problems like the flu and the most commonly used tests cannot detect the most recent infections. The alternative tests for HIV RNA are expensive and there are no clear guidelines on when to use them.
Researchers analysed data from 1562 men who have sex with men enrolled in the Amsterdam Cohort Studies. At 17,271 study visits the men tested HIV-negative, while at 175 visits they had recently acquired HIV. The men had provided data on their health (including whether they had experienced 14 symptoms associated with HIV seroconversion) and sexual behaviour.
The researchers examined the factors associated with acquiring HIV. Two multivariable logistic regression models were constructed: one including only symptoms and one combining symptoms with other risk factors, using generalised estimating equations.
Several risk scores were tested. The optimal one included both symptoms and risk factors, assessed over the previous six months:
- Fever 1.6
- Swollen lymph nodes 1.5
- Oral thrush 1.7
- Weight loss 0.9
- Receptive anal sex without a condom 1.1
- More than five sexual partners 0.9
- Gonorrhoea 1.6.
The cut-off for the score is 1.5, meaning that any man with one of the first three symptoms or gonorrhoea would be recommended to be tested for acute HIV. Equally, a combination of any two (or more) factors would be an indication that further testing is appropriate.
Using this risk score with members of the Amsterdam Cohort would indicate that 24% should be tested for HIV RNA. In terms of sensitivity, the risk score identified 76% of men with acute infection.
Validating the risk score with a different cohort, the Multicenter AIDS Cohort Study (MACS) from the United States, 12% of participants would be recommended for further testing, but the risk score was less sensitive – 56% of men with acute infection would be identified.
The area under the curve (AUC) was 0.82 for the Amsterdam Cohort and 0.78 for MACS.
Different score cut-offs could be used, depending on the local context, local prevalence of acute infection, cost of a false positive and cost of a false negative. A lower cut-off would result in fewer cases of acute infection being missed but a larger proportion of men requiring testing.
Awareness, diagnosis and referral
Researchers and agencies in the Netherlands have also been working to raise awareness in Dutch gay men of early HIV infection, its symptoms, and the importance of prompt testing and treatment. An online media campaign, including videos and testimonials, has encouraged men to use an online symptom checker and risk assessment tool.
Last year, the researchers reported that over 50,000 people had completed the symptom checker during a nine-month period. Of those, 5598 people (10%) were advised to test for acute HIV and 1093 (20%) downloaded a referral letter for an Amsterdam clinic providing rapid HIV RNA testing.
At CROI, the researchers outlined their rapid diagnostic and referral strategy which aims to link people with acute infection to care as rapidly as possible.
Over an 18-month period 237 gay men with possible acute HIV infection attended for testing. Of these, 112 had been referred by the online symptom checker, 72 had attended for routine STI screening, 16 had been referred by a general practitioner and 37 had come through another route.
Of the 237 men, 31 were excluded, generally because their symptoms or sexual behaviour did not in fact correspond to an elevated risk of acute HIV.
Testing consisted of a rapid point-of-care HIV antibody test, a point-of-care HIV RNA test (GeneXpert) which provides results in 90 minutes, and a laboratory fourth generation HIV antigen/antibody test.
This showed that 17 men (8.3%) had either acute or recent HIV infection. There were ten cases of acute infection, seven of recent infection, two of established infection, and 184 men were HIV-negative. Whereas eight of the ten acute infections would have been identified with the fourth-generation test alone, two were only identified with the RNA test.
The median time from a man arriving at the clinic to getting all results was 3.2 hours. All HIV-positive patients were referred to an HIV treatment centre for immediate HIV treatment.
For the moment, the diagnostic strategy and the online symptom checker are based on an earlier version of the risk score, with a longer list of questions. In the coming months, these will be updated to reflect the risk score described above.
The researchers believe this can enhance early diagnosis and immediate treatment, while reducing the number of people needing RNA testing.
Dijkstra M et al. Risk- and symptom-based screening improves identification of acute HIV infection. Conference on Retroviruses and Opportunistic Infections (CROI 2017), Seattle, abstract 886, 2017.
Davidovich U et al. Highly successful engagement in an acute HIV-infection awareness campaign in Amsterdam. 21st International AIDS Conference, Durban, abstract LBPE031, 2016.
Dijkstra M et al. Implementation of a rapid trajectory to identify acute HIV infection in Amsterdam. Conference on Retroviruses and Opportunistic Infections (CROI 2017), Seattle, abstract 887, 2017.