Original Article
Absence of HIV Infection in Blood Donors with Indeterminate Western Blot Tests for Antibody to HIV-1
N Engl J Med 1990; 322:217-222January 25, 1990
- Abstract
- Abstract
To determine whether apparently healthy persons who have had repeatedly reactive enzyme immunoassays and an indeterminate Western blot assay for antibody to the human immunodeficiency virus type 1 (HIV-1) are infected with HIV-1 or HIV-2, we studied 99 such volunteer blood donors in a low-risk area of the country. The subjects were interviewed about HIV risk factors. Coded blood specimens were tested again for HIV-1 antibody (by two different enzyme immunoassays, a Western blot assay and a radioimmunoprecipitation assay) and for HIV-2 antibody by enzyme immunoassay, for HIV-1 by the serum antigen test, for HIV-1 by culture, for human T-cell leukemia virus Type I or II antibody by enzyme immunoassay, and for sequences of HIV DNA by the polymerase chain reaction.
Of the 99 blood donors, 98 reported no risk factors for HIV-1 infection; 1 donor had used intravenous drugs. After a median of 14 months (range, 1 to 30) from the time of the initial test, 65 subjects (66 percent) were still repeatedly reactive for HIV-1 antibody on at least one immunoassay. In 91 subjects (92 percent) the Western blot results were still indeterminate, whereas in 8 they were negative. No donor met the criteria for a positive Western blot assay for HIV-1, and none had evidence of HIV-1 or HIV-2 infection on culture or by any other test.
We conclude that persons at low risk for HIV infection who have persistent indeterminate HIV-1 Western blots are rarely if ever infected with HIV-1 or HIV-2. (N Engl J Med 1990; 322:217–22.)
Article Activity
- Article
LICENSED enzyme immunoassay kits for screening the blood of volunteer blood donors for antibody to the human immunodeficiency virus type 1 (HIV-1) have been available since March 1985.1 The blood from donors who have been found to be repeatedly reactive on an enzyme immunoassay for HIV-1 antibody has not been used in transfusion or manufactured into other products capable of transmitting infectious agents.2 To verify the presence of HIV-1 antibody in a repeatedly reactive sample, the Western blot assay3 has most often been used as a confirmatory test in the United States.4 This assay typically reveals six to nine characteristic bands if antibodies to HIV-1 proteins of different molecular weights are present and no bands if such antibodies are absent.5 This testing sequence has revealed a low seroprevalence of Western blot—positive donations (0.018 percent of 15 million blood donations to the American Red Cross between April 1985 and May 1988)6 and has been effective in reducing the risk of transmission of HIV-1 infection by blood transfusion.7 Approximately 0.3 percent of 48 million blood donors who reported no high-risk behavior for HIV-1 infection at the time of donation had repeatedly reactive enzyme immunoassays,8 , 9 but the majority of these donors have subsequently tested negative on Western blotting. However, 13 to 48 percent have one or two bands characteristic of HIV-1 on Western blotting.8 , 9 Usually the reactivity is only to one or more of the HIV-1 core proteins (p17, p24, and p55), and therefore the result does not meet the definition of either a positive specimen (with any two of the following bands present: p24, gp41, and either gp120 or gp160 bands)10 or a negative specimen (with no bands present). Such specimens are therefore labeled indeterminate, for lack of a better term. To date, it is likely that 19,000 to 69,000 volunteer blood donors in the United States have had HIV-1—antibody test results that are indeterminate.
The clinical importance of these indeterminate Western blot results is poorly understood; thus, counseling the donors is extremely difficult. To determine whether volunteer blood donors with indeterminate results on Western blotting for HIV-1 are infected with HIV, we evaluated a group of such donors extensively by interview and a number of serologic and virologic assays. In addition, we obtained information about previous vaccinations, exposure to animals, and current medications for correlation with specific band patterns found on Western blots considered to be indeterminate with respect to HIV infection.
Methods
Donors
Between July 1986 and September 1988, approximately 507,169 units of blood from an estimated 233,477 donors were tested for HIV-1 antibody at the American Red Cross blood center in St. Paul and the Memorial Blood Center of Minneapolis. These two facilities supply blood to approximately 95 percent of the hospitals in Minnesota. Approximately 58 percent of the donors lived in the Minneapolis—St. Paul metropolitan area and 42 percent in rural Minnesota, North Dakota, South Dakota, Iowa, or Wisconsin. This region is considered to be an area of low HIV-1 prevalence on the basis of an annual incidence rate of the acquired immunodeficiency syndrome (AIDS) of less than 4.3 cases per 100,000 members of the population.11
Approximately 64.1 percent of the blood donations during this period were screened for HIV-1 antibody with use of the enzyme immunoassay kit for antibody to the lymphadenopathy-associated virus (Genetic Systems, Seattle), and 35.9 percent with the enzyme immunoassay kit for antibody to the human T-cell lymphotropic virus Type III (HTLV-III) (Abbott Laboratories, N. Chicago). Donors whose test results were repeatedly reactive on enzyme immunoassay and indeterminate on a Western blot assay using a different manufacturer's HIV-1 viral lysate from that used in the enzyme immunoassay were eligible for enrollment in the study. For purposes of the study, a positive Western blot assay for HIV-1 was defined by the presence of any two of the following bands: p24, gp41, and either gp120 or gp160.10 A donor's assay results were considered to be indeterminate for HIV-1 if the Western blot showed at least one band characteristic of HIV-1 (p17, p24, p31, gp41, p51, p55, p66, gp120, or gp160) but did not meet the criteria for a positive result.
Of the 507,169 donations, 1468 (0.29 percent) were repeatedly reactive on enzyme immunoassay and hence were tested by the Western blot technique. Of these, 10 were positive, 312 were indeterminate, and 1146 were negative on Western blotting (Table 1Table 1
Results of Testing of Blood Donations for HIV-1 Antibody, July 1986 to September 1988.). Donors were ineligible for the study if they had a Western blot that showed only bands not characteristic of HIV-1 or if they were repeatedly reactive on enzyme immunoassay and indeterminate on Western blotting using viral lysate from the same manufacturer but Western blot—negative when another manufacturer's viral lysate was used. Donors who had indeterminate Western blot results before the determination of eligibility were not asked about high-risk behavior for HIV acquisition. Of 312 donors with indeterminate results, 183 (59 percent) were eligible for the study. These donors were contacted by letter and telephone between July and November 1988 and asked to participate in a follow-up interview. Ninety-nine (54 percent) of the 183 eligible donors agreed to participate. The interval between the original donation and the follow-up evaluation was at least six months for 87 (88 percent) of the 99 participants (median, 14 months; range, 1 to 30 months). Written informed consent was obtained from all participants, who were assured that access to their test results, histories, and personally identifying information would be limited to the interviewer and the principal investigator. However, the donors were told that in the event of a Western blot result that was confirmed as positive for HIV-1, the Minnesota Department of Health would be informed, as required by state law. The interviews were conducted in private by a staff person from the blood bank who was trained to ascertain HIV risk factors. The interviewer drew 40 ml of blood for additional testing and administered a standardized questionnaire to assess the presence of HIV risk factors, the sexual history, any previous vaccinations, any exposure to animals, and the medical history, including current medications. Demographic characteristics of nonparticipants were obtained from history cards completed by the donors.From March 1985 through March 1988, 17 blood donors who were HIV-1—positive on Western blotting were identified through the two blood centers (including the 10 donors identified during the period of this study). The Minnesota Department of Health had previously evaluated 16 of these 17 donors,8 and blood specimens from the 16 donors served as HIV-1—positive controls in the assays. Eleven whole-blood donors who were antibody-negative on enzyme immunoassay were selected randomly and interviewed at the time of donation; blood specimens from these donors were used to provide HIV-1—negative assay controls. All blood specimens were coded and tested blindly.
The data were analyzed by standard univariate methods, including the chi-square test and Fisher's exact test, two-tailed, and an analysis of variance for the age comparisons.
Laboratory Testing
Two enzyme immunoassays to screen for HIV-1 antibody (Genetic Systems and Abbott Laboratories) were performed on the original and follow-up serum samples for which the Western blot results were indeterminate, according to the manufacturers' directions. Various unlicensed Western blot assays for HIV-1 had been performed on the original serum specimens at the time of donation; licensed HIV-1 Western blots (Dupont Diagnostics, Wilmington, Del.) were performed on all the follow-up serum samples. All Western blots were read by three independent observers, and the final interpretations were based on agreement between at least two of the three readers.
The following tests were also performed on all follow-up serum specimens: HIV-1 p24 and gp41 antibody enzyme immunoassay (sensitivity, 100.0 percent; specificity, 99.95 percent),12 , 13 which uses recombinant p24 and gp41 antigens (Envacor, Abbott Laboratories), HIV-1/HIV-2 combination-antibody enzyme immunoassay (sensitivity, 100.0 percent and 99.5 percent for known specimens of HIV-1 and HIV-2, respectively; specificity, 99.8 percent)14 (Abbott), HTLV-I/II antibody enzyme immunoassay (Abbott),15 HIV-1 radioimmunoprecipitation assay,16 and HIV-1 p24 antigen enzyme immunoassay (Abbott).17
In addition, serum samples from all donors were cultured for HIV-1 by a method described in detail elsewhere.18 Briefly, 1×107 donor peripheral-blood mononuclear cells were cocultivated for 35 days with HIV-1—seronegative peripheral-blood mononuclear cells stimulated with phytohemagglutinin in RPMI-1640 medium containing 20 percent fetal-calf serum and 5 percent interleukin-2. To assess the presence of HIV-1, the culture supernatants were assayed for p24 antigen by enzyme immunoassay (Abbott) twice a week. Cultures were considered to have productive HIV-1 if HIV-1 antigen was detected in two serial supernatants with the latter sampling demonstrating at least a twofold increase in reactivity. The sensitivity of this culture technique is 99 percent in detecting HIV-1 in the peripheral-blood mononuclear cells of asymptomatic persons with positive test results on Western blotting.18
The culture supernatants were also assayed on day 21 for reverse transcriptase activity with an assay described elsewhere.19 The presence of HIV-1 or another retrovirus in the culture was suspected if (1) the particle-associated reverse transcriptase activity measured with a poly [rA]: oligo [dT]12–18 nucleotide template was more than 10,000 cpm per 1.5 ml of supernatant; and (2) this activity was at least three times greater than the activity measured with the poly [dA]: oligo [dT]12–18 template.
The amplification and detection of HIV sequences by the polymerase chain reaction were performed in blinded fashion on DNA specimens from the 99 donors with indeterminate results on Western blotting, the 11 antibody-negative donors, and 14 of the 16 antibody-positive donors. Two gag primer pairs, SK38/3920 and SK145/101, were used with their respective probes, SK19 and SK102. The combination of the SK38/39 primer pair with the SK19 probe can routinely detect 10 copies of HIV-1 in 1 μg of human placental DNA (equivalent to 150,000 cells) in our laboratory; it has a sensitivity of at least 97 percent in detecting HIV-1 gag sequences in the DNA of peripheral-blood mononuclear cells from persons seropositive for HIV-1 antibody.21 The combination of the SK145/101 primer pair with the SK102 probe has a similar sensitivity for HIV-1 detection22 and is also capable of detecting a gag sequence of HIV-2 (HIV-2 isolate ROD). However, measurement of the diagnostic sensitivity and specificity of this combination in detecting HIV-2 must await the availability of a larger number of samples from persons with HIV-2.
The polymerase-chain-reaction assays were performed as follows: DNA samples (1 μg) from the equivalent of 150,000 peripheral-blood mononuclear cells from the donor were subjected to 30 cycles of denaturation (95°C, 30 seconds), reannealing (55°C, 30 seconds), and extension (72°C, 60 seconds) in the presence of 50 pmol of each HIV primer pair, 2.5 units of Taq polymerase, and 20 nmol of each deoxynucleotide triphosphate in a total volume of 100 μl of reaction buffer (50 mM potassium chloride, 10 mM TRIS–hydrochloric acid [pH 8.3], and 2.5 mM magnesium chloride). Approximately 30 percent of the amplified product was denatured for 5 minutes at 95°C and then subjected to liquid hybridization with specific 32Pend-labeled probes (250,000 cpm per reaction, specific activity of 3 to 5 μCi per millimole) for 15 minutes at 55°C. Half of the hybridized product was then electrophoresed on a 10 percent polyacrylamide gel for one hour. Autoradiographs of the gels were obtained after a three-hour and overnight exposure of Kodak X-OMAT AR film at -70°C. Positive controls consisted of DNA samples from homosexual men positive for HIV-1 antibody. Negative controls consisted of DNA samples from healthy persons negative for HIV-1 antibody and reagent samples without DNA (in order to detect contamination of the reagent by HIV sequences).23 The polymerase chain reaction was also performed on every DNA sample with use of a primer pair (GH 26/27) that amplifies a conserved region of HLA-DQ alpha,24 to determine whether the DNA in the crude cell lysates was of sufficient quality for amplification.
At least one aliquot of frozen peripheral-blood mononuclear cells for each donor was analyzed in duplicate for each HIV primer pair. For half the donors, a second aliquot of frozen peripheral-blood mononuclear cells was analyzed in the same manner. A specimen was considered to be HIV-positive by the polymerase chain reaction if HIV sequences were detected by both primer pairs in duplicate or detected repeatedly by at least one primer pair in duplicate. If a specimen was positive in one of two amplifications, a third amplification was performed to determine positivity or negativity. A specimen was considered to be HIV-negative by the polymerase chain reaction if there were no detectable HIV sequences when cells were analyzed in duplicate for each of two primer pairs.
Results
Demographic and Epidemiologic Characteristics
There was no significant difference between the 99 participants and the 84 nonparticipants with regard to demographic characteristics on the basis of the donor history cards and band patterns on the original Western blot assays (Tables 2Table 2
Comparison of Participants and Nonparticipants in the Study, According to Demographic Characteristics, 1986–1988.* and 3Table 3
Band Patterns of Study Participants and Nonparticipants on Western Blotting.). The mean ages of the male and female participants whose Western blot results were indeterminate were 40.8 years (range, 18 to 72) and 36.8 years (range, 17 to 69), respectively. Fifty-six percent lived in the Minneapolis—St. Paul metropolitan area. Of the donors with indeterminate Western blots, one man had a history of intravenous drug use and of a sexual partner with a history of intravenous drug use. None of the donors reported homosexual or bisexual behavior or a history of gonorrhea or syphilis. None were positive for hepatitis B surface antigen at the time of blood donation. Of the 49 male donors, 41 (84 percent) stated that they had had 5 or fewer female sexual partners in the previous 10 years, 3 (6 percent) had 6 to 10 partners, and 3 (6 percent) had 15 to 50 partners. No information was provided by the remaining two. Of the 50 female donors, 48 (96 percent) had had 5 or fewer male sexual partners in the previous 10 years, 1 (2 percent) had had 6 to 10 partners, and 1 (2 percent) had had between 15 and 50 partners. Nine men and women (9 percent) had received blood transfusions since 1977.When the histories of exposure and the medical histories of the 99 donors with indeterminate Western blot results and the 11 control donors negative for HIV-1 antibody were compared, no significant differences were noted with respect to past illnesses, vaccinations, travel history, or the consumption of raw foods (including raw milk, raw meat, and raw fish). In addition, no donors with indeterminate Western blot results had symptoms suggestive of HIV-1 infection at the time of follow-up.
HIV-1 Enzyme Immunoassay Testing
The original serum samples from 76 donors were repeatedly reactive on enzyme immunoassay for HIV-1 antibody with use of the Genetic Systems kit, as compared with 23 serum samples repeatedly reactive with use of the Abbott kit. Only 3 of 99 serum samples were repeatedly reactive with both kits. After a median follow-up of 14 months (range, 1 to 30 months), samples from 65 donors (66 percent) were still repeatedly reactive for HIV-1 antibody on either the Genetic Systems or the Abbott Laboratories HIV-1—antibody screening enzyme immunoassays (Table 4Table 4
Results of HIV-1—Antibody Testing at Follow-up in Donors with Indeterminate Results on Western Blotting.*). Only 3 of 23 donors (13 percent) who were initially repeatedly reactive according to the Abbott kit were repeatedly reactive on follow-up, as compared with 62 of 76 donors (82 percent) tested with the Genetic Systems kit. No donor had a sample that was repeatedly reactive according to both the Genetic Systems and Abbott kits at the time of follow-up.Western Blot and Radioimmunoprecipitation Assay
In the original serum samples from participants, the most common indeterminate band patterns showed a single p24 band (32 percent), a single p17 band (29 percent), a single p55 band (11 percent), and a combination of the p17 and p55 bands (11 percent) (Table 3). Ninety-two of the 99 samples (93 percent) had bands only to HIV-1 core proteins (p17, p24, and p55), and 3 of the 99 (3 percent) had bands to at least one pol gene protein (p51 or p66). Samples from four donors had faint thin bands in the gp41 or gp160 region, but the bands did not resemble the broad, diffuse bands characteristic of these HIV-1 envelope proteins.
Follow-up testing by Western blot assay revealed that 90 of the 99 samples (91 percent) continued to have indeterminate test results, 8 (8 percent) were negative, and 1 was uninterpretable because of dark background staining (Table 4). There was no noticeable evolution in the band patterns, such as increasing band strength or the development of characteristic envelope bands, in any of these samples (Table 3). Eleven samples had bands to pol gene proteins on follow-up, as compared with three samples originally. However, these additional bands were faint, and not all three observers uniformly interpreted them as present. The initial Western blot for the donor with a history of intravenous drug use showed only a p17 band; the follow-up Western blot, obtained nine months later, demonstrated the same pattern.
Four of the 99 donors (4 percent) had indeterminate results on the radioimmunoprecipitation assay, but the results in the other 95 were negative. The radioimmunoprecipitation assay of one 22-year-old woman revealed only an atypical gp120/160 band. Her original Western blot had only a p17 band, and the follow-up blot 24 months later had p17 and p24 bands. The radioimmunoprecipitation assays of three other donors showed only a p55 band.
Other Results of Assay and Culture
None of the 99 donors were positive for HIV-2 or HTLV-I/II antibody on enzyme immunoassay, for HIV-1 antibody on the recombinant Envacor assay, for HIV-1 on serum testing for p24 antigen, or for HIV-1 on culture with reverse transcriptase or antigen-detection testing. Also, none of these donors had detectable HIV-1 or HIV-2 gag sequences, as determined by the polymerase chain reaction.
Results of Testing in Controls
In contrast, all 16 Western blot—positive blood donors were positive according to all the HIV-1 antibody tests and HIV-1 culture assays used. All of the 14 Western blot—positive donors who were tested by polymerase chain reaction had HIV-1 gag sequences detectable by at least one primer pair (Table 5Table 5
Number of Donors with Detectable HIV DNA Sequences by the Polymerase Chain Reaction.). All the 11 control blood donors who were negative for HIV-1 antibody on enzyme immunoassay were negative on all the above tests.Discussion
In this study, follow-up testing of 99 blood donors with indeterminate Western blot patterns revealed no evidence of HIV-1 or HIV-2 infection according to viral cultures, polymerase-chain-reaction assays, HIV-1 serum antigen testing, or HIV-antibody enzyme immunoassays with recombinant antigens for HIV-1, HIV-2, or both. Most of the indeterminate patterns showed persistent reactivity, with no evidence of seroconversion over time. Thus, our results indicate that volunteer blood donors in a low-prevalence area who report no behavior posing a high risk of HIV in a personal interview and who have repeatedly indeterminate results on Western blotting at both initial and follow-up evaluations are not infected with HIV-1 or HIV-2. Therefore, we believe that no further clinical and serologic follow-up of such donors is generally necessary in the absence of a history of highrisk behavior and clinical symptoms. Recently, the Centers for Disease Control issued a recommendation that "a person whose Western blot test results continue to be consistently indeterminate for at least six months — in the absence of any known risk factors, clinical symptoms, or other findings — may be considered to be negative for antibodies to HIV-1."10 This recommendation," based only on clinical and serologic findings, is substantiated by the virologic data presented in our study, although our data suggest that determination of the appropriate length of the follow-up interval requires further study and that the interval may be less than six months. Furthermore, our conclusions may be applicable to other geographic areas with higher rates of HIV-1 seroprevalence, but additional study is needed to confirm this.
It should be noted, however, that our study results cannot be extrapolated to persons with indeterminate results on Western blotting who engage in behavior posing a high risk of HIV-1 infection. For example, Kleinman et al. reported that 4 of 93 volunteer blood donors with anti-p24 reactivity seroconverted within 8 to 32 weeks of initial testing and later reported high-risk behavior.9 Therefore, persons with apparent risk factors for HIV infection should be retested with standard enzyme immunoassay and Western blot testing at one-to-three-month intervals, tested by other supplemental assays (such as HIV culture, polymerase chain reaction, or antibody tests using HIV-1 recombinant antigens), or both, if available. The fact that no donor in our study was repeatedly reactive on both HIV-1—antibody enzyme immunoassays or reactive on the HIV-1—antibody recombinant enzyme immunoassays suggests that these assays may provide useful information in the interpretation of indeterminate Western blots.
The cause of most atypical HIV-1 Western blot band patterns is unknown, although their presence has been associated with heat-related inactivation of serum samples,25 , 26 in vitro hemolysis,27 elevated bilirubin levels,27 rheumatoid factor,27 polyclonal gammopathy,27 systemic lupus erythematosus,27 and antibodies to DR human lymphocyte antigens (HLA).28 Immunologic cross-reactivity to the core proteins of HIV-1 by other retroviruses, such as bovine immunodeficiency virus, has been described29 and raises the possibility of infection with bovine immunodeficiency virus in humans, perhaps through the consumption of raw milk.30 However, the serum specimens in our study were not inactivated by heat and had no evidence of visible hemolysis or elevated bilirubin levels. None of these donors had a history of autoimmune disease. In this study, previous vaccinations, medications, and types of exposure to animals, including the consumption of raw milk, did not differ significantly between the seronegative and the indeterminate donors. In addition, the majority of the serum samples with indeterminate results on Western blotting were reactive on the Genetic Systems enzyme immunoassay, which uses a viral lysate produced in a CEM cell line that reportedly lacks HLA Class II antigens.31 Thus, we were unable to discern an association between any measure studied and indeterminate status with respect to Western blot results or a specific band. We must caution, however, that the statistical power of our study was limited, since only 11 randomly identified HIV-antibody—negative control subjects were evaluated.
Besides providing insight into the meaning of indeterminate Western blot findings in blood donors, the results of our study have public health implications with respect to the seroprevalence studies and screening programs being conducted in the United States. For example, at least 4 million persons from other populations, such as childbearing women6 , 32 and military recruits,33 are being screened for HIV-1 antibody annually in the United States. It can be expected that many of those screened will be labeled as having indeterminate results on Western blotting on one evaluation. The data presented here indicate that identifiable persons from such populations whose Western blot results are evaluated twice as indeterminate and who are at low risk are not infected with HIV. Thus, the interpretation of seroprevalence data and the counseling of persons identified through screening programs should now be easier.
Supported in part by a research grant from the Centers for Disease Control AIDS Program, Atlanta.
We are indebted to Dr. David Ho at Cedars—Sinai Medical Center, UCLA School of Medicine, for performing additional radioimmunoprecipitation assay analysis.
Source Information
From the Department of Laboratory Medicine and Pathology, University of Minnesota (J.B.J., K.J.S., H.H.B.), the Acute Disease Epidemiology Section, Minnesota Department of Health (K.L.M., M.T.O.), and the Memorial Blood Center of Minneapolis (M.H., H.F.P.), all in Minneapolis; the American Red Cross — St. Paul Region, St. Paul, Minn. (J.B.J., J.C., C.S., W.E.K., R.J.B.); Abbott Laboratories, North Chicago (S.L.S.); and the Department of Infectious Diseases, Cetus Corporation, Emeryville, Calif. (N.J.F., S.Y.K., J.J.S.). Address reprint requests to Dr. Jackson at the Institute of Pathology, Case Western Reserve Medical School, 2085 Adelbert Rd., Cleveland, OH 44106.
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D Chattopadhya, R.K Aggarwal, U.K Baveja, Veena Doda, Sudershan Kumari. (1998) Evaluation of epidemiological and serological predictors of human immunodeficiency virus type-1 (HIV-1) infection among high risk professional blood donors with Western blot indeterminate results. Journal of Clinical Virology 11:1, 39-49
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G. J. J. Van Doornum, M. Buimer, E. Gobbers, P. J. Bindels, R. A. Coutinho. (1998) Evaluation of an expanded two-ELISA approach for confirmation of reactive serum samples in an HIV-screening programme for pregnant women. Journal of Medical Virology 54:4, 285-290
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Takeo Kato, Jun-ichi Suzuki, Makoto Daimon, Hideo Sasaki, Kiichi Ishikawa. (1997) Antibodies to the HIV-1 p17 Protein Cross-React with Human Superoxide Dismutase-2. Biochemical and Biophysical Research Communications 230:1, 184-187
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J. Coll, J. Palazon, H. Yazbeck, J. Gutierrez, C. Aubo, P. Benito, P. Jagiello, H. Maldyk, J. Marrugat, J. Anglada, J. Vivancos, J. Font. (1995) Antibodies to human immunodeficiency virus (HIV-1) in autoimmune diseases: Primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis and autoimmune thyroid diseases. Clinical Rheumatology 14:4, 451-457
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M. G. Marin, F. Lillo, O. E. Varnier, S. Bresciani, A. Molinelli, C. Abecasis, P. A. Bonini, A. Albertini. (1995) Detection of HIV-1 proviral sequences in lymphocytes using a qualitative polymerase chain reaction assay. European Journal of Clinical Microbiology & Infectious Diseases 14:7, 621-625
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