Still no proof for a correlation between the HIV PCR and antibody tests 6 February 2004
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Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

Send response to journal:
Re: Still no proof for a correlation between the HIV PCR and antibody tests

STILL NO PROOF FOR A CORRELATION BETWEEN THE HIV PCR AND ANTIBODY TESTS

In his rapid response, "More on the specificity of PCR and its correlation with the antibody test", 22nd December 2003, Christopher Noble wrote:  "The Perth Group responds:  "In fact it appears that Owens et al were aware that what they called controls were not proper controls.  In their recommendations Owens et al wrote: "For example, the non-diseased population should include persons who are at risk for HIV infection and would be candidates for testing rather than healthy controls", which they used in their analysis."

 

Noble comments:  “Once again the Perth Group display their mind reading abilities and see what the authors of the meta-study "really" meant rather than simply reading the meta-study at face value."

 

Nowhere in the text of the Owens et al paper do the authors confirm or even mention whether any of the studies in their analysis included controls from a "non-diseased population", "at risk for HIV infection".  Under the subtitle, "Recommendations for Study Design" they wrote:  "Many of the studies we analysed had design limitations…incomplete representation of the spectrum of patients in the study population, insufficient sample size, and incomplete reporting of test results.  To increase the generalisability of study results, the study sample should reflect the entire spectrum of disease encountered in the clinical population of interest.  For example, the nondiseased population should include persons who are at risk for HIV infection and would be candidates for testing rather than healthy controls".

 

What would be Christopher Noble's interpretation of the above?

 

Christopher Noble wrote:  "After reading the meta-study the Perth Group should be aware that a large proportion of the studies analysed by Owens et al did indeed include non-diseased populations that were at high risk for HIV infection.  These included homosexual and heterosexual partners of HIV seropositive patients, polytransfused haemophiliacs and thalassemics, and intravenous drug users.  The correlation between antibody and PCR tests remained in these populations".

 

Nowhere in the text  is it mentioned if any of the studies included controls of "non-diseased homosexuals and heterosexual partners of HIV seropositive patients, polytransfused haemophiliacs and thalassemics, and intravenous drug users".  Amongst the references there are several  titles in which such diseases are mentioned.  However:  Owens et al do not mention (1) how many, if any, of these papers were included in their study;  (2) how many, if any, of these studies’ design satisfied all the criteria of the Owens et al analysis

 

Christopher Noble wrote:  "First the Perth Group denied that there were blind-controlled studies that provided evidence for the correlation of antibody and PCR tests for HIV infection and now they come up with more ad hoc excuses for ignoring data that contradicts their beliefs".

 

We have not denied the possibility that such studies may exist but claimed that if such studies exist, apart from that of Defer et al,1 we have been unable to find them.  That is why we have repeatedly asked Christopher Noble to help and give  us a few references in which:  (1) the specificity of the antibody and PCR tests has been proven.  Among other conditions the studies must have proper controls, use suitable gold standards and be blind;  (2) prove a correlation between the antibody and the PCR tests.  Among other conditions the studies must be blind, have proper controls and use antibody and PCR tests with proven specificity.

 

So far, Christopher Noble has failed to provide even one reference.  This is not surprising.  There are two basic scientific reasons for this:

 

(i)                  lack of a gold standard for either test;

(ii)                lack of standardisation of both the antibody and the PCR test.

 

Christopher Noble wrote:  "Their "explanations" that they provide for the correlation between these tests (which they deny anyway just to be safe) are pure speculation without any supporting evidence.  They do not explain the ability of both antibody and PCR tests to distinguish between HIV-1 and HIV-2 infection (1)."

 

Again we have not denied the existence of a correlation between the two tests but claimed that if it exists we have been unable to find proof for it.

 

At present there is ample evidence in support of our oxidative theory of AIDS.  AIDS is associated with high level of antibodies (hypergammaglobulinaemia) and some, if not all, of these antibodies will react with the antigens in the "HIV" test kits.  Thus the hypothesis of a correlation between oxidation and a positive antibody test may not be as pure a speculation as Christopher Noble believes.

 

As we have stated in our rapid response "Is there proof of a correlation between the "HIV" antibody and PCR tests and what may underlie such a correlation?", 11th December 2003, "At present we cannot claim proof that the positive PCR tests are the result of the oxidative stress to which the patients and cultures are exposed.  However, the fact that all the other predictions of this theory have been proven…indicates this may well prove to be the case".

 

If there were two unique retroviruses, "HIV-1" and "HIV-2", as the "HIV" experts claim, then it should be easy "to distinguish between HIV-1 and HIV-2 infection" by the antibody tests and definitely by PCR.  The fact that Christopher Noble could cite only one such reference suggests this is not the case.

 

In the Kannangai et al study2 cited by Noble, according to the Western blot (immunoblot) and PCR status the patients were divided into 5 groups (Table 1).  All were re-tested using an "HIV-2 specific env peptide" ELISA consisting of "11 amino acid sequences from the immunodominant epitope", synthesised by Kannangai et al.

 

Table 1. The mean, standard deviation of absorbance values for different categories of samples tested by HIV-2 specific

 synthetic peptide ELISA and its correlation with HIV-2 PCR a,b. 

Category of samples

No. of samples

ELISA absorbance

Peptide ELISA result

Percentage Concordance

 

 

Mean

SD

POS

NEG

 

HIV-1 PCR and IB POS

30

0.040

0.05

1

29

97

HIV-2 PCR and IB POS

19

1.669

0.735

19

0

100

HIV-1&2 and IB POS

5

1.119

0.769

5

0

100

HIV-2 IB POS; HIV-1&2 PCR NEG

2

0.387

0.388

1

1

50

HIV-1&2 IB POS; HIV-2 PCR NEG

7

0.015

0.0045

0

7

100

a SD, standard deviation; IB, immunoblot; POS, positive; NEG, negative.
b ELISA negatives (n=45) mean OD±SD: 0.056±0.040 (range 0.003–0.157)

 

There are several reasons why one cannot claim Kannangai et al have proven "the ability of both antibody and PCR tests to distinguish between HIV-1 and HIV-2 infection".

 

The first and absolutely necessary condition which Kannangai et al had to satisfy was to have patients which were proven to be infected with either "HIV-1", "HIV-2" or dually infected by means other than their test.  That is, the patients in each of the five groups were indeed infected with the claimed viruses.  However, they could not have obtained such proof.

1. According to Hans Gelderblom “…the bulk of internal proteins of the virion [retroviruses] with molecular weight (mw) between 10,000 d and 30,000 d are group-specific (gs) for viruses originating in a given animal species (gs-spec. antigens). The major protein constituent of mammalian C-type oncornaviruses [retroviruses] with a molecular weight in the range of 30,000 d was found to possess, besides gs spec. antigen, an antigenic determinant that is shared by C-type viruses of many mammalian species including monkeys and was thus termed gs interspecies (gs-interspec.) antigen".3  This leads to antibody cross-reactivity with gag proteins/antigens.  It is accepted that "HIV-1" antibodies cross-react with the HIV-2 antigens and vice versa, the "HIV-2" antibodies cross-react with the "HIV-1" antigens.4  According to Kannangai et al "evidence is emerging that many HIV-1 and HIV-2 dual infections detected by immunoblot may actually be HIV-1 infections with cross-reactivity for HIV-2 bands".

 

According to Gallo  “the antibodies which react with retroviral glycoproteins are not directed against the proteins “but against the carbohydrate moieties on the molecule that are introduced by the host cell as a post-transcriptional event, and which are therefore cell-specific and not virus-specific”.5  According to other eminent retrovirologists including Robin Weiss and Reinhard Kurth “we conclude that the majority (if not all) of normal human sera contain naturally occurring heterophile antibodies that react with the carbohydrate moieties of retrovirus envelope antigens”.6  In a study published in 1996 it was reported that up to 8% of "non-infected blood donors had reactivity to nonglycosylated gp41 epitopes". 7  Obviously since sick individuals have elevated levels of antibodies the prevalence of such reactivity would be much higher.

 

Given the above facts one would have to conclude that Kannangai et al had no proof:  (i) how many, if any, of their patients having a positive immunoblot were infected and with which virus, "HIV-1", "HIV-2", or both to begin with;  (ii) how many, if any, of the patients who had a positive "HIV-2" peptide ELISA were indeed infected with this virus.

 

2. Kannangai et al wrote:  "The HIV-1 and the HIV-2 specific nested PCRs were carried out as described previously (Delwart et al., 1995; Damond et al., 1998)”.  In Damond et al8 one reads "HIV-2 is rarely isolated from peripheral blood mononuclear cells (PBMCs) [from HIV-2 antibody positive individuals] and the detection rates of proviral DNA by PCR amplification vary between 50 and 80%…"  Because of the low correlation between the antibody and the PCR tests, Damond et al "evaluated a new human immunodeficiency virus type 2 (HIV-2) DNA amplification strategy based on peripheral blood mononuclear cell long PCR (XL PCR) followed by nested PCR amplification.  The primers used were located in the highly conserved long terminal repeat in the pol regions of the genome.  Five primer pairs corresponding to different regions of the HIV-2 env gene were used in the nested step". Samples from 42 HIV-2 positive patients were tested and amplification with one primer was considered a positive PCR.

 

If a positive HIV-2 antibody test was proof for HIV-2 infection and if the primers were amplifying the env gene, then:  (i) each primer pair should have given positive results with all 42 samples;   (ii) all samples should have tested positive with all primer  pairs.  This is not the case.  Two samples were not amplified by any of the five primer pairs. Two samples were amplified by only two primer pairs;  Four samples were positive with three primer pairs;  five samples were positive with four primer pairs and twenty nine with five primer pairs.

 

 Numbers of the 42 samples amplified by 2/5 - 5/5 primer pairs

No. of primer pairs

2

3

4

5

Samples

2

4

5

29

 (An additional 2 samples were NOT amplified by any of the 5 primer pairs)

 

Comment:  Since both the PCR and the antibody tests are very sensitive, if they detect HIV-2 a perfect correlation should exist between the PCR and the antibody test as Christopher Noble claims.  However:  (i) as mentioned, the PCR is positive only in 50-80% of antibody positive patients;  (ii) since Damond et al spared no effort to obtain a positive PCR and since they used a highly sensitive "strategy" which allowed them to bypass HIV-2 "diversity", if the amplified DNA was HIV-2, all patients should have had a positive result with all primers.  Instead, 26% (11/42) of the patients had a positive result with some but not all primers, and in 5% (2/42) the results were negative with all primers.  As mentioned, amplification with even one primer was considered a positive PCR.  However, the finding of a positive PCR with a few primers, or even with all five primers if they do not amplify the entire env gene, is not proof the full env gene is present much less the entire HIV genome, that is, HIV infection.  Since Kannangai et al used the same HIV-2 PCR method as Damond's et al then, given the many shortcomings of this method, one must conclude that neither group had proof that a positive PCR was proof for HIV-2 infection.

 

It must also be pointed out that the Kannangai et al study was not blind and the number of patients tested at least in some groups was extremely low.

 In conclusion, at present:  (i) there are no "antibody and PCR tests [which are able] to distinguish between HIV-1 and HIV-2 infection";  (ii) there is no proof for a correlation between the HIV antibody and PCR tests;  (iii) there is no proof that HIV-1 and HIV-2 infection can be defined in molecular terms.

 

Christopher Noble wrote:  ""The Perth Group continue to respond with lies.  For instance they write "At least Montagnier in his  1997 interview to Djamel Tahi admitted that he had not isolated HIV and in his view neither had Gallo".  In fact, in this interview Montagnier specifically states that he did isolate HIV".

 

In 1983 Montagnier claimed he had isolated HIV because he could pass it to cultures containing lymphocytes originating from a healthy blood donor and umbilical cord.  He made the same claim at the beginning of Djamel Tahi's interview,  "we did isolation because we "passed on" the virus".9  By “passing” he meant detection of reverse transcription (RT) in the culture which contained lymphocytes from his patient, BRU, and in the co-cultures with lymphocytes or supernatants from the BRU culture and  lymphocytes from a healthy donor or umbilical cord.  He claimed the detection of RT activity was proof for isolation because this activity was "truly specific of retroviruses".  However, after repeated questioning he admitted that reverse transcriptive activity is not specific to retroviruses and thus, indirectly, that he did not isolate HIV.

 

In addition, detection of an enzymatic activity, even if specific to retroviruses, is not evidence for isolation.  For example, the measurement of cardiac or liver enzymes in cases of myocardial infarction or hepatitis respectively cannot be construed as "isolation" of the heart or liver.

 

The dictionary meaning of "isolation" derives from the Latin insulatus, and refers to the act of separating an object from all other matter that is not that object and not the detection of a characteristic of the object such as an enzyme.  "Purification" means to obtain something free from impurities.  In this context isolation is the same as purification.  After repeated questioning Montagnier admitted, "I repeat, we did not purify".

 

It is also of interest that in the same interview Montagnier stated:  "….Gallo said: "They [Montagnier et al] have not isolated the virus"".  Yet in a most recent collaborative publication by Gallo and Montagnier,10 they wrote:  "In early 1983, a clear-cut isolate was obtained in Paris”.   When we sought clarification (see Addendum) we were informed:  Our “Montagnier/Gallo commentary on HIV/AIDS has not been accepted for publication…After considering its focus, content, and interest, we did not think it suitable for our diverse readership.  We decided not to have it evaluated by external reviewers”.

 

Christopher Noble wrote: "I am still waiting for an honest answer to all of my previous questions".

 

Repeat, although maybe not to his liking, we have honestly answered all Christopher Noble's questions.  If he wishes he may repeat them and we will answer them again.

 

REFERENCES 

1. Defer C, Agut H, Garbarg-Chenon A, Moncany M, Morinet F, Vignon D, et al. Multicentre quality control of polymerase chain reaction for detection of HIV DNA. AIDS 1992;6:659-663.

2. Kannangai R, Ramalingam S, Prakash KJ, Abraham OC, George R, Castillo RC, et al. A peptide enzyme linked immunosorbent assay (ELISA) for the detection of human immunodeficiency virus type-2 (HIV-2) antibodies: an evaluation on polymerase chain reaction (PCR) confirmed samples. Journal of Clinical Virology 2001;22:41-6.

3. Bauer H, Daams JH, Watson KF, Molling K, Gelderblom H, Schafer W. Oncornavirus-like particles in HeLa cells. II. Immunological characterization of the virus. Internat J Cancer 1974;13:254-261.

4. Gnann JW, Jr., McCormick JB, Mitchell S, Nelson JA, Oldstone MB. Synthetic peptide immunoassay distinguishes HIV type 1 and HIV type 2 infections. Science 1987;237:1346-9.

5. Kalyanaraman VS, Sarngadharan MG, Bunn PA, Minna JD, Gallo RC. Antibodies in human sera reactive against an internal structural protein of human T-cell lymphoma virus. Nature 1981;294:271-273.

6. Lower J, Davidson EA, Teich NM, Weiss RA, Joseph AP, Kurth R. Heterophil human antibodies recognize oncovirus envelope antigens: epidemiological parameters and immunological specificity of the reaction. Virol 1981;109:409-17.

7. Sayre KR, Dodd RY, Tegtmeier G, Layug L, Alexander SS, Busch MP. False-positive human immunodeficiency virus type 1 western blot tests in noninfected blood donors. Transfusion 1996;36:45-52.

8. Damond F, Loussert-Ajaka I, Apetrei C, Descamps D, Souquiere S, Lepretre A, et al. Highly sensitive method for amplification of human immunodeficiency virus type 2 DNA. J Clin Microbiol 1998;36:809-11.

9. Tahi D. Did Luc Montagnier discover HIV?  Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 1998;5:30-34.

10. Gallo RC, Montagnier L. The discovery of HIV as the cause of AIDS. N Engl J Med 2003;349:2283-5.

 

 

 

 

ADDENDUM

Unpublished commentary on Gallo RC, Montagnier L. The discovery of HIV as the cause of AIDS. New England Journal of Medicine 2003;349:2283-5.

It is a pity that Robert Gallo and Luc Montagnier1 do not provide readers of the Journal with references to back up their many claims regarding the proof for the existence of HIV and its role in AIDS.  Especially since many of their claim are questionable.  For example:

 

(1)     "…the causative relationship between HIV and AIDS was accepted by the scientific and medical community…"  Not everybody in the scientific community accepted that they proved the existence of HIV and its causative role in AIDS.2-4 Also, acceptance of a theory does not prove the theory correct.

 

(2)     "In early 1983, a clear-cut isolate [HIV] was obtained in Paris…".  However, in 1984 Gallo and his colleagues said that Montagnier and his group's 1983 evidence did not prove "true isolation".5  As late as 1997 Jaap Goudsmit wrote: "The BRU lymph node was first cultured in early January 1983 and, on January 15, it shed an enzyme absolutely unique to the lentivirus group…The BRU virus grew slowly and with difficulty, but its identity and activity were reported in the May 20, 1983 issue of Science…The Pasteur Group was widely acclaimed but very worried.  In the world of virology, finding a new virus is not enough:  You must propagate and isolate the organism for analysis by other virologists.  The French had not yet isolated their new lentivirus";6

 

(3)     "…reverse transcriptase - the enzyme that is present in all retroviruses…".  It is true that this enzyme is present in all retroviruses, including lentiviruses and that the detection of reverse transcription was considered by Montagnier proof for HIV isolation.  But it is also true that the enzyme is not unique to these viruses, much less to lentiviruses.  Furthermore, all the HIV experts including Gallo and Montagnier have proven the presence of the enzyme indirectly, that is, by transcription of the synthetic template-primer An.dT15.  However, even before the AIDS era, at least Gallo and the principal and second authors of the Montagnier 1983 study were aware that this template-primer can be transcribed by cellular DNA polymerases7-9 as was proven by Montagnier himself in 1984.10

 

(4)     "…the centres for Disease Control and Prevention (CDC) reported cases of AIDS in patients with haemophilia who had received only filtered clotting factors, which seemed to eliminate the possibility that the agent was a micro-organism larger than a virus".  If AIDS is caused by filtered factor VIII it does not mean that the cause is a virus.  The cause could be something even smaller than a virus.  If as Gallo and Montagnier claim at the basis of the clinical manifestations of AIDS is a decrease in T4 cells, then given the fact that Robin Weiss and the CDC have shown that in haemophiliacs, "the abnormal T-lymphocyte subsets are a result of the intravenous infusion of factor VIII concentrates per se, not HTLV-III [HIV] infection"11, 12 then one would have to conclude that the cause of AIDS in haemophiliacs is factor VIII and not HIV.  Furthermore if:  (a) as some of the most eminent HIV experts, including Montagnier claim that:  "gp120 is crucial to HIV's ability to infect new cells", and gp120 is present only in the HIV particles spikes (knobs);13, 14  (b) to date nobody has proven the existence of spikes in the cell-free HIV particles;15 (c) Factor VIII is made from cell-free plasma;  (d) according to the  CDC “drying of HIV-infected human blood or other body fluids reduces the theoretical risk of environmental transmission to that which has been observed--essentially zero";16 (e) Factor VIII is a freeze dried powder several months or even years old before use;  then if the cause of AIDS in haemophiliacs is a virus, the virus would have to be other than HIV.

 

(5)     "The growth of the putative virus in T-cell lines was an enormous step, facilitating the development of a blood test for HIV, which…produced convincing evidence of the association between HIV infection and AIDS".  To obtain antigens for the development of the blood test (antibody test) one must obtain a large amount of the virus and, as Montagnier points out,17 purify the virus.  In 1997 Montagnier acknowledged that in 1983 his team did not purify the virus, and in his view, neither did Gallo's in 1984.17  Neither has anybody else since.  Even if there is proof beyond reasonable doubt that the antigens in the antibody test are HIV proteins, proof must exist that they do not cross-react with antibodies which are elicited by agents other than HIV.  However, the specificity of the antibody tests has never been proven and, due to the lack of a gold standard, cannot be proven.3  Furthermore, Essex and his colleagues have shown that antibodies to carbohydrate-containing antigens such as lipoarabinomannan, which are present in all mycobacteria and fungi, react with the antigens in the HIV tests.18  Since the vast majority of the opportunistic infections which signify AIDS are caused by mycobacteria or fungi a correlation between a positive antibody test and AIDS may be present in the absence of HIV19, 20  Most importantly, even if an association between HIV and AIDS existed, such an association is not proof for causation.

 

(6)     "…AIDS had already appeared as a long-lasting disease, with an extremely long time between exposure to the agent (through blood or sexual activity) and the profound state of immune suppression characterised by the occurrence of opportunistic infections or cancers".  If the causative agent of AIDS is sexually transmitted, then the agent cannot be HIV.  The main absolute necessary property of sexually transmitted agents is bidirectionality, that is transmission from the passive to the active partner and vice versa.  To date there is no proof that this is the case for HIV.  In 1984 Gallo and his colleagues reported that "Of eight different sex acts, seropositivity correlated only with receptive anal intercourse…and with manual stimulation of the subject's rectum (receptive "fisting")…and was inversely correlated with insertive anal intercourse".21  Two years later they confirmed their 1984 findings"  "In this analysis, only receptive rectal intercourse, douching, rectal bleeding…were significant predictors (p<.05) of anti-HTLV-III positivity…We found no evidence that other forms of sexual activity contributed to the risk".22  In a 1994 review of all the major studies conducted in gay men the authors concluded:  "(1) unprotected anogenital receptive intercourse poses the highest risk for the sexual acquisition of HIV-1 infection;  (2) anogenital insertive intercourse poses the highest risk for the sexual transmission of HIV-1 infection…(5) no or no consistent risk for the acquisition of HIV-1 infection has been reported regarding other sexual practices such as anogenital insertive intercourse and oroanal sex…"23

 

          Since only the passive partner becomes seropositive then, at least in gay men, HIV, like pregnancy, can be sexually acquired but not sexually transmitted.  The largest, longest, best designed and executed studies conducted in the USA and Africa show that HIV is not heterosexually transmitted.24-27

 

Eleni Papadopulos-Eleopulos  Biophysicist, Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia

Valendar F. Turner  Consultant Emergency Physician, Department of Emergency Medicine, Royal Perth Hospital, Perth, Western Australia

John M Papadimitriou  Professor of Pathology, University of Western Australia, Perth, Western Australia

Barry A. P. Page  Physicist, Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia

Helman Alfonso  Lecturer, School of Public Health, Curtin University, Western Australia

David Causer Physicist, Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia

Sam Mhlongo  Head & Chief Family Practitioner, Family Medicine & Primary Health Care, Medical University of South Africa, Pretoria, South Africa

Todd Miller  Research Assistant Professor,  Department of Medicine, Division of

Cardiology, University of Miami School of Medicine, Florida, United States of America

Andrew Maniotis, Department of Pathology, University of Illinois at Chicago, United States of America

Christian Fiala  Specialist in Gynaecology, Vienna, Austria

REFERENCES

1.             Gallo RC, Montagnier L. The discovery of HIV as the cause of AIDS. New England Journal of Medicine 2003; 349:2283-5.

2.             Duesberg PH. Retroviruses as carcinogens and pathogens: Expectations and reality. Cancer Research 1987; 47:1199-1220.

3.             Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Is a positive Western blot proof of HIV infection? Bio/Technology 1993; 11:696-707.

4.             Papadopulos-Eleopulos E. Reappraisal of AIDS: Is the oxidation caused by the risk factors the primary cause? Medical Hypotheses 1988; 25:151-162.

5.             Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, Isolation,and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS. Science 1984; 224:497-500.

6.             Goudsmit G. Viral Sex-The Nature of AIDS. New York: Oxford University Press, 1997.

7.             Sinoussi F, Mendiola L, Chermann JC. Purification and partial differentiation of the particles of murine sarcoma virus (M. MSV) according to their sedimentation rates in sucrose density gradients. Spectra 1973; 4:237-243.

8.             Toplin I. Tumor Virus Purification using Zonal Rotors. Spectra 1973:225-235.

9.             Weissbach A, Baltimore D, Bollum F. Nomenclature of eukaryotic DNA polymerases. Science 1975; 190:401-402.

10.           Rey MA, Spire B, Dormont D, Barre-Sinoussi F, Montagnier L, Chermann JC. Characterization of the RNA dependent DNA polymerase of a new human T-lymphotropic retrovirus (lymphadenopathy associated virus). Biochemical and Biophysical Research Communications 1984; 121:126-33.

11.           Jason JJ, McDougal S, Holman RC, et al. Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody. Journal of the American Medical Association 1985; 253:3409-3415.

12.           Ludlam CA, Steel CM, Cheingsong-Popov R, et al. Human T-Lymphotropic Virus Type-III (HTLV-III) Infection in Seronegative Haemophiliacs after Transfusion of Factor VIII. Lancet 1985; II:233-236.

13.           Haseltine WA, Wong-Staal F. The molecular biology of the AIDS virus. Scientific Medicine 1988; 259:34-42.

14.           Gougeon ML, Laurent-Crawford AG, Hovanessian AG, Montagnier L. Direct and indirect mechanisms mediating apoptosis during HIV infection: contribution to in vivo CD4 T cell depletion. Immunology 1993; 5:187-194.

15.           Layne SP, Merges MJ, Dembo M, et al. Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus. Virology 1992; 189:695-714.

16.           CDC. Fact sheet on HIV transmission. Fact sheet on HIV transmission 1994; January.

17.           Tahi D. Did Luc Montagnier discover HIV?  Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 1998; 5:30-34.

18.           Kashala O, Marlink R, Ilunga M, et al. Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabinomannan. Journal of Infectious Diseases 1994; 169:296-304.

19.           Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D, Page B. HIV antibody tests and viral load - more unanswered questions and a further plea for clarification. Current Medical Research and Opinion 1998; 14:185-186.

20.           Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D. The Isolation of HIV: Has it  really been achieved? Continuum 1996; 4:1s-24s.

21.           Goedert JJ, Sarngadharan MG, Biggar RJ, et al. Determinants of retrovirus (HTLV-III) antibody and immunodeficiency conditions in homosexual men. Lancet 1984; 2:711-6.

22.           Stevens CE, Taylor PE, Zang EA, et al. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City. Journal of the American Medical Association 1986; 255:2167-2172.

23.           Caceres CF, van Griensven GJP. Male homosexual transmission of HIV-1. AIDS 1994; 8:1051-1061.

24.           Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous heterosexual, HIV-1 discordant couples in Rakai, Uganda. Lancet 2001; 357:1149-1153.

25.           Kamali A, Quigley M, Nakiyingi J, et al. Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial. Lancet 2003; 361:645-52.

26.           Padian NS, Shiboski SC, Glass SO, Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology 1997; 146:350-357.

27.           Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, et al. Global voices on HIV/AIDS. Heterosexual transmission of HIV in Africa is no higher than anywhere else. British Medical Journal 2002; 324:1035.

 

 

Competing interests: None declared