Spanish doctors have reported a case of hidden, or “occult” HIV infection in the March 1st edition of Clinical Infectious Diseases. The case concerned a patient who was hospitalised with multiple opportunistic infections and a CD4 cell count of only 4 cells/mm3. HIV antibody tests were repeatedly negative, although tests showed that the patient had an HIV viral load of over 100,000 copies/ml.
Updated HIV testing guidelines issued by the World Health Organization (WHO) recommend the use of enzyme immunoassay (EIA) HIV antibody tests. The use of antibody tests alone to diagnose HIV could, however, mean that patients who have very recently been infected with HIV, and who have not yet developed antibodies to the infection, may go undiagnosed. This is of significant public health concern as patients with very recent HIV infection (often called acute infection) are very infectious and may account for up to 50% of all HIV transmissions.
Because of this, routine HIV viral load testing has been suggest as a way of diagnosing patients who would be missed by routine antibody tests.
But doctors in Madrid encountered a case which showed the potential advantages of HIV viral load testing in other situations.
In November 2005 a 28 year old man was hospitalised with a severe chest infection and a four-month history of thrush. Kaposi’s sarcoma was also diagnosed and tests showed the man’s chest infection was caused by pneumocystis jiroveci pneumonia (formerly known as PCP).
However, both second- and third-generation EIA HIV antibody tests were negative and an HIV Western blot test had only indeterminate results.
A fourth generation antibody test did yield a positive result and the patient’s p24 antigen level was 17.2pg/ml.
Tests also showed that the patient had an HIV viral load of 122,000 copies/ml, and was infected with a subtype-B, CCR5-tropic strain of HIV.
Antiretroviral therapy was initiated and after three weeks the patient’s viral load fell to 12,000 copies/ml. But his Kaposi’s sarcoma progressed rapidly and the patient developed significant lung disease leading to his death two weeks later.
A total of 16 cases of HIV infection with negative HIV antibody results have been reported in medical journals. The investigators note that such cases, like the one they report, all involved patients with extremely weak immune systems and high HIV viral loads.
“Host characteristics, rather than specific HIV features, seem to be the main determinants of these ‘occult’ HIV infections”, note the investigators.
They add that such cases have implications both for the development of a vaccine and for public health.
“Pooling of HIV antibody EIA-negative samples with HIV RNA screening on a routine basis” has proved, the investigators note, a good way of enhancing HIV diagnostics and is cost effective. They conclude, “our case, albeit rare, further supports the use of HIV RNA testing to exclude HIV infection in HIV-seronegative individuals.”
de Lejarazy RO et al. HIV-1 infection in persistently HIV-1 seronegative individuals: more reasons for HIV RNA screening. Clin Infect Dis 46: 785, 2008.