An urgent need for introduction of fourth-generation Ag–Ab based EIA for detection of HIV infection

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Dear Editor, Detection of antibodies against HIV is the cornerstone of HIV screening assays. The major drawback of antibody based assay is that they turn reactive only on seroconversion following the initial viremia. Fourth-generation enzyme immunoassays (EIA) has the ability to simultaneously detect the p24 antigen and conventional HIV antibodies1 and thereby reduce the window period and the risk of transmission of infection. Between Jan 1997 and Aug 1999 (32 months), we screened 10,204 units of blood by third-generation (MICROLISA HIV1/2, J. Mitra) as well as fourth-generation Ag–Ab assays (Genscreen Ultra HIV Ag–Ab, Biorad) at a large blood bank in a tertiary care hospital in Central India on an unlinked anonymous basis. All units were also assayed for other transfusion transmitted infections (TTI). 27 units tested positive for HIV infection by the fourth-generation assay whereas 25 units tested positive by antibody based third-generation assays. Thus, we were able to detect two additional HIV positive units by fourth-generation assays that would otherwise have been missed by third-generation assays. HIV infections in these two cases were further confirmed by HIV RNA load by real time PCR. National guidelines on HIV testing permit the use of simple and rapid antibody detection kits depending on the specific strategy employed for HIV diagnosis namely blood banking, surveillance, voluntary testing or PMTCT etc. The main reasons for not insisting on EIA based assays routinely are equipment costs, technical difficulties and absence of electricity in remote locations. Marks et al suggest that in USA approximately 21% of individuals with HIV infection are unaware of their status, and may account for more than 50% of new transmissions of the disease.2 With early identification of HIV disease there are potential reductions in disease transmission and improvement in assay sensitivity. The current third-generation assays, antibodies can be detected in most individuals within 4–6 weeks of viral transmission. However, the p24 antigen is detectable before an antibody response during the initial burst of viral replication (Fig. 1). The risk of infection from persons with acute early infection is reported to be greater due of the elevated viral load. Fig. 1 Figure depicting the serological response and the time frame for detection by different assay methods to HIV infection. India has seen a definite decadal trend in HIV infection and it is now imperative to ensure that not even a single HIV infection occurs either vertically or during transfusion simply because the existing antibody based assays failed to detect an early HIV infection. Many countries of the European Union like France and Germany have already introduced fourth-generation assays as the initial point of care. Most of the states in USA too have followed suit. Since most of the blood banks and laboratories of larger hospitals in India have facilities for carrying out EIA, its appropriate time for initial introduction of fourth-generation HIV assays in blood banks and PMTCT programs nationally. Subsequently, the same should be extended for all the HIV testing strategies (I, IIa, IIb and III, NACO, India).3 It is also reiterated that the cost per test of fourth-generation assays are comparable to the third-generation and cheaper to some rapid kits (Table 1). Table 1 Cost per test for different assays for detection of HIV infection.