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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 analyzed 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 behavior.

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 generalized estimating equations.

Several risk scores were tested. The optimal one included both symptoms and risk factors, assessed over the previous 6 months:

• Oral thrush 1.7;
• Fever 1.6;
• Gonorrhea 1.6;
• Swollen lymph nodes 1.5;
• Receptive anal sex without a condom 1.1;
• Weight loss 0.9;
• More than 5 sexual partners 0.9.

The cut-off for the score is 1.5, meaning that any man with 1 of the first 4 risk factors would be recommended to be tested for acute HIV. Equally, a combination of any 2 (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 among 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 9-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 sexually transmitted infection 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 behavior did not in fact correspond to an elevated risk for acute HIV.

Testing consisted of a rapid point-of-care HIV antibody test, a point-of-care HIV RNA test (GeneXpert) that 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 10 cases of acute infection, 7 of recent infection, 2 of established infection, and 184 men were HIV-negative. Whereas 8 of the 10 acute infections would have been identified with the fourth-generation test alone, 2 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 center for immediate HIV treatment.

For now, 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 HIV diagnosis and immediate treatment, while reducing the number of people needing RNA testing.

3/19/17

Sources

M Dijkstra, GJ de Bree, I Stolte, et al. Risk- and symptom-based screening improves identification of acute HIV infection. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 886.

Dijkstra M et al. Implementation of a rapid trajectory to identify acute HIV infection in Amsterdam. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 887.

M Dijkstra,E Hoornenborg, U Davidovich, et al. Highly successful engagement in an acute HIV-infection awareness campaign in Amsterdam. 21st International AIDS Conference. Durban, July 18-22, 2016. Abstract LBPE031.