HIV-1 sensitivity to zidovudine and clinical outcome

Boucher, Charles A.; Lange, Joep M. A.; Maxeiner, Horst G.; Habermehl, K. O.; Grünewald, Th.; B, Ruf; Tudor‐Williams, Gareth; Clair, M H St; McKinney, Ross E.; Maha, Mary; Walter, Emmanuel B.; Santacroce, Shiela; Mintz, Mark; O’Donnell, Karen; Rudoll, Tracy; Vavro, Cindy; Connor, Edward; Wilfert, Catherine M.

doi:10.1016/0140-6736(92)90922-p

Cited by 4 publications

(1 citation statement)

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“…Conversely, there was no correlation between the ICsos for AZT and for PFA, nor between those for ddl or ddC and PFA. Previous studies on individual isolates obtained by cultivation on cell lines showed cross-resistance between AZT and other anti-HIV drugs to be rare and mainly limited to other nucleosides containing a 3'-azido group (Larder et aI., 1990;Rooke et el., 1991;Gao et aI., 1992 (Boucher and Lange, 1992). We performed a TCID so determination on the viral isolate in every case, and used a similar infectious dose of virus in all experiments.…”

Section: Discussionmentioning

confidence: 99%

Cross-Resistance between AZT, ddl and other Antiretroviral Drugs in Primary Isolates of HIV-1

Cox

Aperia

Sandström

et al. 1994

Antivir Chem Chemother

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Primary isolates of human immunodeficiency virus type 1 (HIV-1) were tested for sensitivity to 3′-azido-3′-deoxythymidine (AZT), 3′-fluoro-3′-deoxythymidine (FLT), 2′,3′-dideoxyinosine (ddl), 2′,3′-dideoxycytidine (ddC), and phosphonoformate (PFA) in peripheral blood mononuclear cells (PBMC). Forty-eight isolates from HIV-1-infected patients treated with AZT for various lengths of time were investigated. More than half of the patients harboured virus resistant to AZT after treatment. There was no correlation between resistance and length of therapy. A significant correlation between resistance to AZT and reduced susceptibility to ddl and ddC was apparent. These results indicate that development of resistance to AZT is common in patients treated with AZT and may be associated with reduced sensitivity to ddl and ddC.

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Section: Discussionmentioning

confidence: 99%

Cross-Resistance between AZT, ddl and other Antiretroviral Drugs in Primary Isolates of HIV-1

Cox

Aperia

Sandström

et al. 1994

Antivir Chem Chemother

View full text Add to dashboard Cite

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Development of In Vitro resistance to zidovudine is likely to be clinically significant

Tudor‐Williams

Emery

1992

Reviews in Medical Virology

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Duesberg

Rasnick

1998

Genetica

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Almost two decades of unprecedented efforts in research costing US taxpayers over $50 billion have failed to defeat Acquired Immune Deficiency Syndrome (AIDS) and have failed to explain the chronology and epidemiology of AIDS in America and Europe. The failure to cure AIDS is so complete that the largest American AIDS foundation is even exploiting it for fundraising: 'Latest AIDS statistics-0,000,000 cured. Support a cure, support AMFAR.' The scientific basis of all these unsuccessful efforts has been the hypothesis that AIDS is caused by a sexually transmitted virus, termed Human immunodeficiency virus (HIV), and that this viral immunodeficiency manifests in 30 previously known microbial and non-microbial AIDS diseases. In order to develop a hypothesis that explains AIDS we have considered ten relevant facts that American and European AIDS patients have, and do not have, in common: (1) AIDS is not contagious. For example, not even one health care worker has contracted AIDS from over 800,000 AIDS patients in America and Europe. (2) AIDS is highly non-random with regard to sex (86% male); sexual persuasion (over 60% homosexual); and age (85% are 25-49 years old). (3) From its beginning in 1980, the AIDS epidemic progressed non-exponentially, just like lifestyle diseases. (4) The epidemic is fragmented into distinct subepidemics with exclusive AIDS-defining diseases. For example, only homosexual males have Kaposi's sarcoma. (5) Patients do not have any one of 30 AIDS-defining diseases, nor even immunodeficiency, in common. For example, Kaposi's sarcoma, dementia, and weight loss may occur without immunodeficiency. Thus, there is no AIDS-specific disease. (6) AIDS patients have antibody against HIV in common only by definition-not by natural coincidence. AIDS-defining diseases of HIV-free patients are called by their old names. (7) Recreational drug use is a common denominator for over 95% of all American and European AIDS patients, including male homosexuals. (8) Lifetime prescriptions of inevitably toxic anti-HIV drugs, such as the DNA chain-terminator AZT, are another common denominator of AIDS patients. (9) HIV proves to be an ideal surrogate marker for recreational and anti-HIV drug use. Since the virus is very rare (< 0.3%) in the US/European population and very hard to transmit sexually, only those who inject street drugs or have over 1,000 typically drug-mediated sexual contacts are likely to become positive. (10) The huge AIDS literature cannot offer even one statistically significant group of drug-free AIDS patients from America and Europe. In view of this, we propose that the long-term consumption of recreational drugs (such as cocaine, heroin, nitrite inhalants, and amphetamines) and prescriptions of DNA chain-terminating and other anti-HIV drugs, cause all AIDS diseases in America and Europe that exceed their long-established, national backgrounds, i.e. > 95%. Chemically distinct drugs cause distinct AIDS-defining diseases; for example, nitrite inhalants cause Kaposi's sarcoma, cocaine causes weight los...

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HIV-1 sensitivity to zidovudine and clinical outcome

Cited by 4 publications

References 7 publications

Cross-Resistance between AZT, ddl and other Antiretroviral Drugs in Primary Isolates of HIV-1

Cross-Resistance between AZT, ddl and other Antiretroviral Drugs in Primary Isolates of HIV-1

Development of In Vitro resistance to zidovudine is likely to be clinically significant

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