No Evidence of HIV-1 Infection in Seronegative Hemophiliacs and in Seronegative Partners of Seropositive Hemophiliacs through Polymerase Chain Reaction (PCR) and Anti-NEF Serology

Summary

We prospectively studied a well-characterized cohort including 60 seronegative hemophiliacs or von Willebrand’s disease patients, 6 seronegative female sexual partners of seropositive hemophiliacs, 59 seropositive hemophiliacs or von Willebrand’s disease patients and 2 seropositive partners of seropositive hemophiliacs (used as positive controls), and 117 seronegative low risk individuals (used as negative controls). PCR assay, performed in peripheral blood mononuclear cells using three primer pairs in the gag, pol, LTR regions, showed no positive results in the 60 seronegative patients, in the 6 seronegative partners of seropositive patients and in the 117 seronegative low risk individuals, while PCR was positive with at least one primer pair in 53 (87%) of 61 seropositive patients. Anti-nef serology (Westem-blot) was negative in seronegative patients, in seronegative partners of seropositive patients and positive in 58% out of the seropositive individuals. These results strongly suggest an absence of HIV-1 infection in individuals with a lastingly negative HIV serology.

• References

• 1 Allain JP. Prevalence of HTLV-III/LAV antibodies in patients with hemophilia and in their sexual partners in France. N Engl J Med 1986; 315: 517-518
• 2 Smiley ML, White GC, Becherer P. et al Transmission of human immunodeficiency virus to sexual partners of hemophiliacs. Am J Hematol 1988; 28: 27-32
• 3 Kreiss JK, Kitchen LW, Prince HE. et al Antibody to human T-lymphotropic virus type III in wives of hemophiliacs: evidence for heterosexual transmission. Ann Intern Med 1985; 102: 623-626
• 4 Kim HC, Raska K, Clemow L. et al Human immunodeficiency virus infection in sexually active wives of infected hemophilic men. Am J Med 1988; 85: 472-476
• 5 Ranki AM, Valle SL, Krohn M. et al Long latency precedes overt seroconversion in sexually transmitted human immunodeficiency virus infection. Lancet 1987; 2: 5889-5893
• 6 Imagawa DT, Lee MH, Wolinski SM. et al Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods N Engl J Med 1989; 320: 1458-1462
• 7 Saiki RK, Scharf S, Faloona F. et al Enzymatic amplification of betaglobin genomic sequences and restriction site analysis for diagnosis of sickle-cell anemia. Science 1985; 230: 1350-1354
• 8 Kwok S, Mack DH, Mullis KB. et al Identification of human imunodeficiency virus sequences by using in vitro enzymatic amplification and oligomer cleavage detection. J Virol 1987; 61: 690-694
• 9 Ou CY, Kwok S, Mitchell SW. et al DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science 1988; 239: 295-297
• 10 Loche M, Bach B. Identification of HIV-infected seronegative individuals by a direct diagnostic test based on hybridisation to amplified viral DNA. Lancet 1988; 2: 418-421
• 11 Wolinski SM, Rinaldo CR, Kwok S. et al Human immunodeficiency virus type 1 (HIV-1) infection. A median of 18 months before a diagnostic Western blot. Ann Intern Med 1989; 111: 961-972
• 12 Ameisen JC, Guy B, Lecoq JP. et al Persistent antibody response to the HIV-1 negative regulatory factor in HIV-1 infected seronegative persons. N Engl J Med 1989; 320: 241-242
• 13 Soriano V, Hewlett I, Tor J, Clotet B, Epstein J, Foz M. Silent HIV infection in heterosexual partners of seropositive drug abusers in Sapin. Lancet 1990; i: 860
• 14 Hewlett IK, Laurian Y, Epstein J, Allain JP. Analysis by PCR of transmission of HIV from infected hemophiliacs to their sex partners and children. Vth International Conference on AIDS, 1989 (abstract MAO 33)
• 15 Eyster ME, Goedert J, Kumar R. Failure of the polymerase chain reaction (PCR) to detect viral HIV-1 DNA by amplification of a gag segment in hemophiliacs with HIV antibodies. Vth International Conference on AIDS, 1989 (abstract TBP 82)
• 16 Moncany MLJ, Berthier A, Ferries S, Montagnier L. Early detection of HIV infection by PCR before seroconversion in multitransfused seronegative haemophiliacs and sexual partners. Sixth International Conference on AIDS, San Francisco, 1990 (Th A 14)
• 17 Jason J, Ou CY, Moore JL. et al Prevalence of human immunodeficiency virus type 1 DNA in hemophilic men and their sex partners. J Infect Dis 1989; 160 (05) 789-794
• 18 De Ronde A, Reiss P, Dekker J. et al Seroconversion to HIV-1 negative regulation factor. Lancet 1988; ii: 574
• 19 Centers for Disease Control: Classification system for human T-lymphotropic virus type III/lymphadenopathy-associated virus infections. MMWR 1986; 35: 334-339
• 20 Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon M. Nucleotide sequence of the Aids virus. Cell 1985; 40: 9-17
• 21 Ranki A, Jarvinen K, Valle SL, Nurmilaakso P, Krohn K. Antibodies to recombinant HIV-1 nef protein detected in HIV-1 infection as well as in non-risk individuals. J AIDS 1989; 3: 348-355
• 22 Taylor GR. HIV detection by DNA amplification. J Clin Pathol 1988; 41: 1244-1246
• 23 Markoulatos P, Ferris S, Karagiorga-Logana M, Kordossi A, Montagnier L, Moncany MLJ. Study of HIV infection by PCR in seronegative multitransfused beta-thalassemiac patients. Sixth International Conference on AIDS; San Francisco: 1990. (FA 353)
• 24 Lifson AR, Stanley M, Pane J. et al Detection of human immunodeficiency virus DNA using the polymerase chain reaction in a well-characterized group of homosexual and bisexual men. J Infect Dis 1990; 161: 436-439
• 25 Lefrere JJ, Mariotti M, Courouce AM, Rouger P, Salmon C, Vittecoq D. Polymerase chain reaction testing of HIV-1 seronegative at-risk individuals. Lancet 1990; i: 1400-1401
• 26 Mariotti M, Lefrere JJ, Noel B. et al DNA amplification of HIV-1 in seropositive individuals and in seronegative at-risk individuals. AIDS 1990; 4: 633-637
• 27 Lefrère JJ, De Montalembert M, Mariotti M, Girot R, Salmon C, Rouger P, Rey J. Absence of DNA sequences in seronegative poly transfused thalassemic patients. Vox Sang, in press
• 28 Shoebridge GI, Gatenby PA, Nightingale BN. et al Polymerase chain reaction testing of HIV-1 seronegative at-risk individuals. Lancet 1990; ii: 180-181
• 29 Hackson JB, Kwok SY, Hopsicker JS. et al Absence of HIV-1 infection in antibody-negative sexual partners of HIV-1 infected hemophiliacs. Transfusion 1989; 29 (03) 265-267
• 30 Lefrere JJ, Richard D, Courouce AM. et al Risk factors of HIV seropositive subjects detected through blood donation in France. Transfusion 1989; 29: 84-86
• 31 Horsburgh C, Ou CY, Jason J. et al Duration of human immunodeficiency virus infection before detection of antibody. Lancet 1989; ii: 637-641
• 32 Van Der Meer J, Daenen S, Van Imhoff GW, de Wolf JT, Halie MR. Absence of seroconversion for HTLV-III in haemophiliacs intensively treated with heat treated factor VIII concentrate. Br Med J 1986; 292: 1049
• 33 Jackson JB, Balfour HH. Hemophiliacs with HIV seroconversion associated with heat-treated products. Are they actively infected?. JAMA 1989; 261: 1275
• 34 Gluckmann JC, Fretz-Foucault C, Rouzioux C. et al Lack of anti-p27 nef antibody detection in HIV seronegative high risk people. AIDS 1989; 3 (12) 855
• 35 Reiss P, De Ronde A, Lange JMA. et al Antibody response to the viral negative factor (nef) in HIV-1 infection: a correlate of levels of HIV-1 expression. AIDS 1989; 3: 227-233