Researchers publish details of multiresistant HIV patient
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《英国医生杂志》
Researchers have published clinical and sequencing details of a unique variant of HIV in a patient who is resistant to several classes of antiretroviral drugs and who rapidly developed AIDS, after media reports of a possible new 搒uper-strain?of the virus (Lancet 2005;365:1031-8).
The patient, a man in his 40s from New York, was given a diagnosis of HIV-1 infection in December 2004 after he had had fever, pharyngitis, weakness, and fatigue the previous month. Earlier he had tested negative for HIV-1 antibodies on several occasions between September 2000 and May 2003. His illness progressed to AIDS within 20 months—and perhaps as little as four months—of infection. The case was first publicised at a press conference in New York last month because of the possible public health implications of a rapidly progressing strain of HIV with multiple drug resistance and then discussed at the 12th retroviral conference in Boston (BMJ 2005;330:498, 5 Mar).
Detailed analysis of the virus showed that it was resistant to three of the four major classes of antiretroviral drugs: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. Viruses usually become less virulent when they acquire drug resistance. However, the replication capacity of the patient抯 HIV-1 was 136% in comparison with a median of 100% derived from a large number of wild type viruses. This indicated that despite its multidrug resistance the virus replicated as well as most wild type, drug susceptible viruses.
Rapid progression to AIDS after acute HIV-1 infection has been described previously, as has the transmission of multidrug resistant viruses. However, Martin Markowitz, of the Aaron Diamond AIDS Research Center at Rockefeller University, New York, and one of the authors of the case report, said: 揟he unique feature in this case is the convergence of two uncommon factors: the transmission of a multidrug resistant HIV-1 variant and the extremely rapid clinical course to AIDS.?He said that the case was in the top 0.5% in terms of rapidity of disease if 12 months was assumed as the duration of his infection.
Viral sequence analysis indicated that the patient抯 virus was subtype B, and the relative homogeneity of the viral population was consistent with early HIV-1 infection. Phylogenetic analysis of a nucleotide sequence from the viral pol gene and from 30 newly infected individuals and five reference HIV-1 strains showed that the viral sequence of the new case was unique. No match was found on the centre抯 sequence database. 揃ecause of its unique features, this pol sequence is now being compared with those in the database at the Los Alamos National Laboratory and in various commercial laboratories with the hope of finding a closely related HIV-1 that might provide an epidemiological link to this case,?the report said.
揟he rapid clinical course of the patient抯 illness could be explained by the properties of his unique HIV-1 variant,?Dr Markowitz said, adding that genetic studies on the case were still under way.
Treatment options for the patient are limited: enfuvirtide and efavirenz are the only two antiretroviral drugs that can provide full activity against his virus. He has been started on a multidrug regimen, including enfuvirtide and efavirenz. Tracing of his sexual contacts has also begun.
An accompanying editorial warned: 揟his case serves as a reminder that HIV remains a frighteningly versatile foe, one that can mutate to escape immune attack or to acquire drug resistance with surprising speed. One lesson to be drawn from this case, therefore, is that despite all the advances that have been made in understanding this virus and all the progress that has been made in developing new drugs, prevention remains the most effective strategy to combat HIV, especially prevention efforts that target high-risk groups, such as men who have sex with men, intravenous drug users, and sex workers and their clients.?/p>(Susan Mayor)
The patient, a man in his 40s from New York, was given a diagnosis of HIV-1 infection in December 2004 after he had had fever, pharyngitis, weakness, and fatigue the previous month. Earlier he had tested negative for HIV-1 antibodies on several occasions between September 2000 and May 2003. His illness progressed to AIDS within 20 months—and perhaps as little as four months—of infection. The case was first publicised at a press conference in New York last month because of the possible public health implications of a rapidly progressing strain of HIV with multiple drug resistance and then discussed at the 12th retroviral conference in Boston (BMJ 2005;330:498, 5 Mar).
Detailed analysis of the virus showed that it was resistant to three of the four major classes of antiretroviral drugs: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. Viruses usually become less virulent when they acquire drug resistance. However, the replication capacity of the patient抯 HIV-1 was 136% in comparison with a median of 100% derived from a large number of wild type viruses. This indicated that despite its multidrug resistance the virus replicated as well as most wild type, drug susceptible viruses.
Rapid progression to AIDS after acute HIV-1 infection has been described previously, as has the transmission of multidrug resistant viruses. However, Martin Markowitz, of the Aaron Diamond AIDS Research Center at Rockefeller University, New York, and one of the authors of the case report, said: 揟he unique feature in this case is the convergence of two uncommon factors: the transmission of a multidrug resistant HIV-1 variant and the extremely rapid clinical course to AIDS.?He said that the case was in the top 0.5% in terms of rapidity of disease if 12 months was assumed as the duration of his infection.
Viral sequence analysis indicated that the patient抯 virus was subtype B, and the relative homogeneity of the viral population was consistent with early HIV-1 infection. Phylogenetic analysis of a nucleotide sequence from the viral pol gene and from 30 newly infected individuals and five reference HIV-1 strains showed that the viral sequence of the new case was unique. No match was found on the centre抯 sequence database. 揃ecause of its unique features, this pol sequence is now being compared with those in the database at the Los Alamos National Laboratory and in various commercial laboratories with the hope of finding a closely related HIV-1 that might provide an epidemiological link to this case,?the report said.
揟he rapid clinical course of the patient抯 illness could be explained by the properties of his unique HIV-1 variant,?Dr Markowitz said, adding that genetic studies on the case were still under way.
Treatment options for the patient are limited: enfuvirtide and efavirenz are the only two antiretroviral drugs that can provide full activity against his virus. He has been started on a multidrug regimen, including enfuvirtide and efavirenz. Tracing of his sexual contacts has also begun.
An accompanying editorial warned: 揟his case serves as a reminder that HIV remains a frighteningly versatile foe, one that can mutate to escape immune attack or to acquire drug resistance with surprising speed. One lesson to be drawn from this case, therefore, is that despite all the advances that have been made in understanding this virus and all the progress that has been made in developing new drugs, prevention remains the most effective strategy to combat HIV, especially prevention efforts that target high-risk groups, such as men who have sex with men, intravenous drug users, and sex workers and their clients.?/p>(Susan Mayor)