Primary HIV-1 infection : : diagnostic, prognostic, and therapeutic aspects

Abstract: Primary HIV-1 infection (PHI) is usually defined as a mononucleosis-like illness associated with seroconversion to HIV. In earlier studies using I st generation antibody tests, the duration of the 'window period' from infection to detection of specific HIV-antibodies, could be 2 to 3 months, or longer. We evaluated currently available tests for HIV-antibody, using sequential sera obtained from PHI patients and found that seroconversion was detected in all patients within 2 weeks after onset of illness by 24 of 27 screening-tests, and that reactivity to all HIV antigens, by Western blot, had appeared within 4 weeks. Thus, the combination of a HIV-antigen-test and a Western blot test provides a convenient strategy by which a PHI diagnosis usually can be confirmed or excluded the same day the patient seeks medical attention. We were able to detect four phases of viremia during primary HIV infection by determination of HIV-RNA in plasma samples from 8 PHI patients not receiving antiviral treatment: (1) increasing viral density - HIV appears in the blood during the week preceding onset of PHI illness, and levels are rapidly increasing reaching a peak at about I week following onset of illness; (2) rapid decay - HIV density rapidly decline over a period of about 2 weeks, associated with lymph gland enlargement, CD8+ lymphocytosis, and appearance of IgG-antibodies; (3) slow decay - the clearance of HIV continue but at a rate of only 1/10 or less of the rate during the rapid decline; (4) steady-state - HIV-Ievels reach a steady-state between production and clearance at an average of 3-4 months following infection. We found a significant correlation between PHI peak HIV-RNA plasma levels and steady-state levels, and steady-state levels have, by others, been shown to correlate with disease outcome. We recorded time from seroconversion to development of AIDS; and the "final endpoint"; time to death from AIDS; in about 200 HIV-infected homo/bisexual men (HS) and injection drug users (IDU) followed for a median time of about 7 years. A more rapid progression of HIV disease was detected in homosexual men than in IDUs; in particular in those who had developed a glandular-fever-like illness at PHI. In summary, a prognostic significance was established for three different variables present even before seroconversion to HIV: mode of transmission, severity of PHI illness, and level of peak viremia at PHI; thus providing support for initiation of antiretroviral treatment in primary HIV infection. Other investigators had reported a benefit of zidovudine monotherapy in PHI, using surrogate markers in short-term studies. We studied the long-term outcome of 21 zidovudine treated PHI patients vs. 64 non-treated controls and found no significant difference between the two groups. We evaluated a three drug combination with two nucleoside analogues and one protease inhibitor, in 9 PHI patients. HIV-RNA declined rapidly to below the detection limit (50 copies/mL), in particular in the 6 patients with treatment started within 10 days from onset of PHI illness: all samples drawn day 69 or later from these were HIV-RNA negative.