Abstract

We report the case of a young man who injected himself intravenously with 2 mL of human immunodeficiency virus (HIV)—infected blood and failed to develop HIV infection.

There is increasing evidence that individuals with documented HIV exposure, for example, prostitutes, intravenous drug users with a known history of needle sharing, newborn infants of HIV-positive mothers, and health care workers who have sustained exposure to HIV-infected blood or body fluids, may remain uninfected (see [1] for a review). The rate of infection after exposure differs remarkably among these groups, depending on the route and, most probably, the amount of virus to which an individual is exposed [2]. The latter has been hard to estimate, especially for persons who have experienced multiple exposures. Also, use of antiretroviral agents as postexposure prophylaxis may affect the rate of infection, as has been shown for percutaneous exposure [3].

Case report. A 22-year-old HIV-seronegative heterosexual man injected himself intravenously with 2 mL of HIV-infected blood. The blood originated from a friend who had a documented HIV infection of 11 years' duration and who, at the time, was being treated with an antiretroviral regimen that included stavudine, lamivudine, and nevirapine. The friend had a virus load of <50 copies/mL, a CD4+ cell count of 300 cells/mL, and no detectable drug-resistance mutations in virus isolated from blood samples (ViroSeq HIV-1; PE Biosystems). At the initial interview, the patient indicated that he had injected himself with the blood with the intention of committing suicide. Anamnestically, there was no history of intravenous drug use, blood transfusion, or homosexual activity.

At 22 h after exposure, the patient was given an intravenous infusion of zidovudine (2 mg/mL), followed by oral therapy with zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), indinavir (800 mg twice daily), ritonavir (100 mg twice daily), and nevirapine (200 mg daily) for the first week, followed by a 3-week period in which the same antiretroviral regimen was administered without nevirapine.

Blood samples were obtained repeatedly during the following 15 months. Serum samples were tested for the presence of antibodies against HIV by ELISA, using a commercial kit (Abbott HIV 1/2 gO EIA; Abbott Laboratories). As can be seen in figure 1, HIV type 1 (HIV-1)—specific antibodies were detectable on day 1 after exposure, but the amount decreased to undetectable levels at day 43 and remained below the test cutoff value. Simultaneously, screening was done for the presence of HIV-1 RNA in EDTA-anticoagulated blood, using an ultrasensitive HIV-1 RNA PCR assay with a sensitivity of 95% for samples with 50 copies/mL and 80% for samples with 20 copies/mL (Cobas AmpliScreen HIV-1 Test, v1.5; Roche Diagnostics). The results of multiple tests for HIV-1 RNA done throughout the observation period were negative.

Figure 1

HIV-specific antibody levels detected by ELISA from day 1 through day 441 after the patient's exposure to HIV-infected blood

Figure 1

HIV-specific antibody levels detected by ELISA from day 1 through day 441 after the patient's exposure to HIV-infected blood

The presence of HIV-1—specific CD4+ T cells was assessed (as a marker of exposure to HIV) by multiparameter flow cytometric assay, using a FastImmune CD4 intracellular cytokine detection kit (Becton Dickinson Laboratories), according to the manufacturer's instructions. Briefly, fresh, heparinized peripheral blood samples were cultured with or without one of the HIV antigen preparations (purified recombinant env-gp120 MN, env-gp160, or gag-p24; Research Diagnostics) and 0.5 µg each of CD28+ and CD49d+ monoclonal antibodies (Becton Dickinson) for a period of 6 h; in the final 5 h, 10 µg/mL brefeldin A (Sigma) was included. Cells were then washed, fixed, permeabilized, and stained using an anti—human IFN-γ kit (FastImmune CD4 intracellular cytokine detection kit; Becton Dickinson) containing the following directly conjugated monoclonal antibodies: IFN-γ (25723.11 fluorescein isothiocyanate), CD69 (L78 phycoerythrin), CD4 (SK3 peridin chlorophyll protein—cychrome 5.5), IgG2a (X39 fluorescein isothiocyanate), and IgG1 (X40 phycoerythrin). Cell samples were analyzed with a FACSCalibur flow cytometry system (Becton Dickinson). Acquisition was performed using CellQuest software, and list-mode multiparameter data files were analyzed using Paint-a-Gate Plus (BD Biosciences). The percentages of HIV-1 antigen—specific IFN-γ—producing CD4+ T lymphocytes were obtained by subtracting the percentages of positive events in the culture stimulated without antigen from the percentages of positive events in the culture stimulated with HIV antigen.

Substantial frequencies of IFN-γ—producing CD4+ T cells were found among gag-p24—stimulated cells (0.37% response among all CD4+ T cells) and env-gp120—stimulated cells (0.44% response) in the first analysis, which was carried out 8 months after exposure. These frequencies decreased to very low (among gag-p24—stimulated cells) or undetectable levels at 15 months after the patient's exposure to HIV (figure 2). In addition, genotype analysis of the chemokine receptor CCR5 gene was performed as described elsewhere [4]. The patient was found to be homozygous for the wild-type allele. Finally, 15 months after exposure to HIV, the patient was still HIV seronegative and had no detectable levels of HIV-1 RNA or HIV-1—specific CD4+ T cells in blood samples.

Figure 2

Detection of HIV type 1 antigen—specific CD4+ T cells at 8 months (A) and 15 months (B) after the patient's exposure to HIV-infected blood.

Figure 2

Detection of HIV type 1 antigen—specific CD4+ T cells at 8 months (A) and 15 months (B) after the patient's exposure to HIV-infected blood.

Discussion. The early steps in the pathogenesis of HIV infection and the role of the immune response to the virus are still under intense investigation. Important information could come from examination of patients who have definitely been exposed to HIV but have not become infected [1]. In contrast to the groups of individuals most commonly exposed to HIV, in the present case, a defined amount of HIV-infected blood had been directly injected intravenously at a known time point. The intravenous injection of the HIV-infected blood obviously did not lead to infection in the patient, as is shown by the lack of HIV-1 RNA and newly produced HIV-specific antibodies in samples obtained over the course of 15 months. Katzenstein et al. [5] reported a similar case, in which a 13-year-old child had received a transfusion of HIV-contaminated packed RBCs. For a period of 15 months, tests for HIV-1 RNA and HIV-specific antibodies were negative, and levels of HIV-1 RNA and HIV-specific antibodies were undetectable. However, our case is unique: an exposure of the patient to the virus could be proven immunologically by the demonstration of a specific CD4+ T cell response to HIV. The patient's positive antibody status at day 1 after exposure reflected the presence of the foreign HIV-1—specific antibodies with which he was inoculated; levels of these antibodies decreased during follow-up and were completely undetectable by day 43 after injection.

Various immunological mechanisms have been described as of importance in host defense against viruses, such as the initial T cell defense directed against foreign peptide antigens expressed on the surface of donor cells. In the present case, rapid recruitment and expansion of these T cells after limited HIV exposure may have eliminated the foreign cells and, thus, may have contributed to the failure of HIV infection to develop. Obviously, only a small amount of free virus was transmitted in the 2 mL of blood with which the patient injected himself, because the donor's virus load was <50 copies/mL. Exposure to low levels of HIV may selectively activate the cellular arm of the immune system (i.e., T helper 1—dominated immune response) without seroconversion occurring, resulting in the presence of strong HIV-specific T cell immunity, which is involved in clearing HIV from infected cells [2, 6]. Finally, that postexposure prophylaxis had an additional effect on the outcome cannot be ruled out, although such therapy was initiated at 22 h after exposure.

In conclusion, in the present case, the absence of infection by HIV was probably related to the small size of the virus inoculum, to the administration of postexposure prophylaxis, and to the development of an HIV-1—specific T cell response. Further knowledge about the potential role of factors combating HIV infection is important to the development of therapeutic and prophylactic vaccine strategies.

Acknowledgments

We thank Ursula Sinzinger and Uschi Zach for technical assistance.

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