Almost one in forty of those who tested HIV-negative in a large clinic cohort in Lilongwe, Malawi, turned out to have acute HIV infection that was too recent to be detected by single or dual rapid antibody test used as the standard method of HIV diagnosis, researchers from the University of North Carolina report in the February 1st edition of the Journal of Infectious Diseases.
They suggest that the sensitivity of HIV testing – its ability to detect HIV infection if it is present – could be improved by using a second rapid test alongside the first one in all patients, not just those who have indeterminate results or who test HIV-positive, or by using p24 antigen testing in the case of indeterminate results. Antigen testing is cheaper and easier to carry out than pooled HIV RNA testing (used in the United States to screen for acute infections).
They note: “Our results confirm that in high incidence settings, the sensitivity of a single test for HIV antibodies can be as low as 96%, due to the presence of significant numbers of previously unrecognized acute HIV infections in the testing population.”
These findings are important because they show that in an African sexually transmitted disease clinic cohort, up to 4% of patients tested for HIV during a one year period was experiencing acute HIV infection but had not yet begun to produce antibodies, suggesting that current HIV testing methods in African settings could be missing a substantial number of highly infectious individuals.
Antibodies to HIV take four to six weeks to appear in most people after infection takes place. Not all infected people experience a seroconversion illness in the weeks after infection.
During acute HIV infection HIV transmission is much more likely than during the chronic phase of infection because virus levels in genital fluids and blood are very high
Since the small population of people experiencing acute HIV infection probably make a disproportionate contribution to the onward transmission of HIV infection, and because the presence of a sexually transmitted infection is likely to further elevate the risk of onward transmission, the extent of `invisible` acute infection in an STD clinic population needed to be assessed, the researchers decided.
They screened 1450 patients presenting with sexually transmitted infections over the course of 21 months at Kamuzu Central Hospital in Lilongwe, Malawi.
Antibody testing was carried out according to the Malawian national protocol, which requires the use of two rapid tests (the Abbott Determine and the Trinity Biotech Unigold test). Patients with concordant positive results were diagnosed as HIV-positive on the spot, while patients with concordant negative results were asked to return one week later to receive the result of a confirmatory test. Patients with discordant results were also asked to return one week later.
All negative and discordant samples were screened using HIV RNA and HIV p24 antigen tests, and Western blot testing was carried out on all samples where HIV RNA was detected.
Twenty one cases of acute infection were identified by HIV RNA testing. In comparison, ultrasensitive p24 antigen testing identified 15 of 17 (88% sensitivity), standard p24 antigen testing identified 12 of 16 (75% sensitivity) and discordant rapid antibody tests identified 7 of 21 (33% sensitivity). This amounted to a prevalence of acute HIV infection among initially seronegative patients of 2.4%.
The authors conclude that in a clinic population of 10,000 patients treated per year, “on the basis of the prevalences observed in this study, use of concordant rapid test results to define positivity would miss ~145 cases of acute HIV infection and 14 cases of established HIV infection but 97 persons would be mistakenly identified as being HIV-positive.”
The authors estimate that if an ultrasensitive p24 assay were used, only 16 of 132 cases of acute HIV infection would be missed.
Fiscus SA et al. Rapid, real-time detection of acute HIV infection in patients in Africa. J Inf Dis 195, 2007.