The New York Case Revisited
The New York Case Revisited
This report provides us with the opportunity to consider whether the details of a single case with highly resistant HIV and rapid disease progression warranted the controversial alarm sounded by the New York City Department of Health. In the wake of a press conference that generated extensive publicity (ACC March 2005, p. 21) and a latebreaker presentation at the Retrovirus Conference (ACC April 2005, p. 34), a case report of the New York City man who rapidly developed AIDS after being infected with a multidrug-resistant HIV has been published.
The general background of the case has already been reported. Succinctly, the patient is an MSM in his late 40s. After developing illness consistent with acute retroviral syndrome in November 2004, he tested HIV-positive in mid-December. Later that month, his CD4 count was 80 cells/mm3 and his viral load was 280,000 copies/mL. Based on a negative HIV test in May 2003, he was referred to the Aaron Diamond AIDS Research Center for evaluation as a possible case of recent HIV-1 infection. By mid-January 2005, he had fatigue, weight loss, and anorexia. Thus, the patient appears to have progressed to AIDS within 4 to 20 months after infection. Further history revealed that he had unprotected anal sex with multiple partners often in conjunction with methamphetamine use before his health declined.
The present report focuses on laboratory analysis of this case. Genotypic testing revealed broad resistance to NRTI, NNRTI, and PIs, and phenotypic testing revealed susceptibility to efavirenz and enfuvirtide only. When highly resistant, HIV often pays a price in measured replicative capacity, which may indicate reduced virulence. Despite the extensive array of mutations in this patient's virus, however, its replication capacity (as determined by a modified Phenosense assay) measured 136% compared with wild-type virus, indicating no loss of fitness. Perhaps explaining the fitness of this highly resistant virus, three distinct tests demonstrated that this patient's viral quasispecies had tropism for both CCR5 and CXCR4; CXCR4-tropic viruses are usually only seen late in HIV infection, and transmission of such viruses is associated with rapid progression. The depletion of CD4 cells in the patient's gastrointestinal tract and blood was especially severe for CXCR4+ T-cells, suggesting that the more virulent CXCR4-tropic variants were dominant. The patient did not have any HLA alleles that have been associated with rapid progression. Finally, phylogenetic analysis revealed that the virus was unique; it could not be matched by available viruses in the Aaron Diamond AIDS Research Center or Los Alamos National Laboratory databases.
The striking feature in this case is the convergence of two uncommon phenomena: the transmission of triple-class-resistant virus and the extremely rapid clinical course to AIDS. In the authors' clear and measured discussion, they state that it cannot be determined yet whether the patient's rapid progression was the result of viral factors, host factors, or a combination of the two. Additional clinical and laboratory investigations may shed some light on this; however, it remains unclear whether the establishment of CXCR4-tropic viruses in newly infected individuals is related to host or viral factors. The authors also acknowledge that at the time of their writing, it was unclear whether this individual represents an isolated case, a confined cluster, or the sentinel signal of more widespread dissemination. Additional follow-up, epidemiologic studies, and time are needed to answer this critical question. Disturbingly, however, the New York Times reported that the New York City Department of Health has identified several new HIV cases with viruses that are potentially related to this patient's; testing is ongoing (Santora M. Tests pending in cases tied to fierce H.I.V. New York Times 2005 Mar 30).
The authors wisely conclude that "Irrespective of the outcome, efforts to prevent HIV-1 transmission need to be intensified, with particular emphasis on the epidemic that is being propelled by the use of methamphetamine. However, in so doing, care should be taken to avoid punitive measures against the populations most vulnerable to HIV-1." An accompanying editorial affirms the decision of the New York City health officials to alert the public about the case, arguing that the investigation will be faster and morbidity may be reduced by encouraging high-risk individuals and potential contacts of the patient to seek testing and by alerting physicians to the possibility of such infections among their patients. In addition, the editorial argues that despite all the advances that have been made in the treatment and basic scientific understanding of HIV, prevention efforts including evidence-based programs that are aimed at promoting safer sexual and drug-use habits, and that are unencumbered by political or moral considerations remain the most effective strategy to combat the virus.
Click here for AIDS Clinical Care subscription information.
This report provides us with the opportunity to consider whether the details of a single case with highly resistant HIV and rapid disease progression warranted the controversial alarm sounded by the New York City Department of Health. In the wake of a press conference that generated extensive publicity (ACC March 2005, p. 21) and a latebreaker presentation at the Retrovirus Conference (ACC April 2005, p. 34), a case report of the New York City man who rapidly developed AIDS after being infected with a multidrug-resistant HIV has been published.
The general background of the case has already been reported. Succinctly, the patient is an MSM in his late 40s. After developing illness consistent with acute retroviral syndrome in November 2004, he tested HIV-positive in mid-December. Later that month, his CD4 count was 80 cells/mm3 and his viral load was 280,000 copies/mL. Based on a negative HIV test in May 2003, he was referred to the Aaron Diamond AIDS Research Center for evaluation as a possible case of recent HIV-1 infection. By mid-January 2005, he had fatigue, weight loss, and anorexia. Thus, the patient appears to have progressed to AIDS within 4 to 20 months after infection. Further history revealed that he had unprotected anal sex with multiple partners often in conjunction with methamphetamine use before his health declined.
The present report focuses on laboratory analysis of this case. Genotypic testing revealed broad resistance to NRTI, NNRTI, and PIs, and phenotypic testing revealed susceptibility to efavirenz and enfuvirtide only. When highly resistant, HIV often pays a price in measured replicative capacity, which may indicate reduced virulence. Despite the extensive array of mutations in this patient's virus, however, its replication capacity (as determined by a modified Phenosense assay) measured 136% compared with wild-type virus, indicating no loss of fitness. Perhaps explaining the fitness of this highly resistant virus, three distinct tests demonstrated that this patient's viral quasispecies had tropism for both CCR5 and CXCR4; CXCR4-tropic viruses are usually only seen late in HIV infection, and transmission of such viruses is associated with rapid progression. The depletion of CD4 cells in the patient's gastrointestinal tract and blood was especially severe for CXCR4+ T-cells, suggesting that the more virulent CXCR4-tropic variants were dominant. The patient did not have any HLA alleles that have been associated with rapid progression. Finally, phylogenetic analysis revealed that the virus was unique; it could not be matched by available viruses in the Aaron Diamond AIDS Research Center or Los Alamos National Laboratory databases.
The striking feature in this case is the convergence of two uncommon phenomena: the transmission of triple-class-resistant virus and the extremely rapid clinical course to AIDS. In the authors' clear and measured discussion, they state that it cannot be determined yet whether the patient's rapid progression was the result of viral factors, host factors, or a combination of the two. Additional clinical and laboratory investigations may shed some light on this; however, it remains unclear whether the establishment of CXCR4-tropic viruses in newly infected individuals is related to host or viral factors. The authors also acknowledge that at the time of their writing, it was unclear whether this individual represents an isolated case, a confined cluster, or the sentinel signal of more widespread dissemination. Additional follow-up, epidemiologic studies, and time are needed to answer this critical question. Disturbingly, however, the New York Times reported that the New York City Department of Health has identified several new HIV cases with viruses that are potentially related to this patient's; testing is ongoing (Santora M. Tests pending in cases tied to fierce H.I.V. New York Times 2005 Mar 30).
The authors wisely conclude that "Irrespective of the outcome, efforts to prevent HIV-1 transmission need to be intensified, with particular emphasis on the epidemic that is being propelled by the use of methamphetamine. However, in so doing, care should be taken to avoid punitive measures against the populations most vulnerable to HIV-1." An accompanying editorial affirms the decision of the New York City health officials to alert the public about the case, arguing that the investigation will be faster and morbidity may be reduced by encouraging high-risk individuals and potential contacts of the patient to seek testing and by alerting physicians to the possibility of such infections among their patients. In addition, the editorial argues that despite all the advances that have been made in the treatment and basic scientific understanding of HIV, prevention efforts including evidence-based programs that are aimed at promoting safer sexual and drug-use habits, and that are unencumbered by political or moral considerations remain the most effective strategy to combat the virus.
Click here for AIDS Clinical Care subscription information.