Bartlett HIV/AIDS Review: June 15, 2005
Bartlett HIV/AIDS Review: June 15, 2005
Markowitz M, Mohri H, Mehandru S, et al. Infection with multidrug resistant, dual-trophic HIV-1 and rapid progression to AIDS: a case report. Lancet. 2005;365:1031-1038 . Investigators from Aaron Diamond AIDS Research Center with multiple collaborators (a total of 18 authors) report "the New York City case."
The Case: In brief, a man in his 40s had a negative HIV serology in May 2003, presented with what may be the acute retroviral syndrome in November 2004, had a positive HIV serology in December 2004, and had a CD4+ cell count of 80 cells/mcL by the end of December 2004. Review of the case suggests that HIV had progressed from transmission to symptomatic AIDS in 4-20 months. More information in sequence is provided as follows:
May 9, 2003: HIV seronegative, CD4+ cell count 1500 cells/mL
November 2004: Fever, pharyngitis, fatigue
December 15, 2004: Physician consultation for recurrent fever, pharyngitis, fatigue, HIV seropositive
December 29, 2004: CD4+ cell count 80 cells/mcL, CD8+ cell count 1012 cells/mcL, VL 280,000 copies/mL
January 12, 2005: Pharyngitis, dysphagia, fatigue, weight loss; Detuned HIV serology positive
February 2, 2005: CD4+ cell count 39 cells/mcL, CD8+ cell count 571 cells/mcL
The HIV strain: The viral isolate in this case was dual trophic, multiply resistant, and had a replication capacity of 136%. Further detailed information is provided in the following listing:
Dual trophic with CCR5 and CXCR4
Resistance test results:
Subtype: B
Conclusion: The authors conclude that this case represents the convergence of multidrug resistance and rapid progression. In view of the case history, which indicates multiple high-risk sexual contacts, the public health ramifications of the case are particularly important.
Comment: This case was the subject of a special late breaking symposium at the 12th Conference on Retroviruses and Opportunistic Infections (CROI). The following points were emphasized:
With respect to the follow-up on this case, the New York City Department of Health and Mental Hygiene has issued the following recommendations based on this case: (1) physicians should be alert to the acute retroviral syndrome, obtain an appropriate risk history, and test for both antibody and viral load; and (2) resistance tests should be done for all newly diagnosed HIV infections. Any cases associated with 3-drug resistance should be immediately reported to the Bureau of HIV/AIDS Prevention and Control. (3) Partner names and contact information should be obtained in all patients with HIV infection. This step is especially true with primary HIV infection, which is associated with increased risk of HIV transmission. For further information, see "HIV/AIDS REPORTING AND PARTNER NOTIFICATION."
Derdelinckx I, Van Laethem K, Maes B, et al. Current levels of drug resistance among therapy-naive HIV-infected patients have significant impact on treatment response. J Acquir Immune Defic Syndr. 2004;37:1664-1666 . The authors obtained blood retrospectively from patients who initiated antiretroviral therapy in 2000. Resistance tests were done in specimens obtained within 3 months before initiating highly active antiretroviral therapy (HAART). Virologic failure was defined as the failure to achieve a viral load of less than 50 copies/mL. Of 6 patients with transmitted resistance, only 2 responded. This finding compares with adequate response by 69 of 74 patients who had no detected transmitted resistance ( P = .001). The authors conclude that resistance profile at baseline in chronically infected patients is important in selection of the HAART. They also note that the proper way to do this study would be prospectively and that this strategy is now being carried out in Europe in: "Strategy to Control Spread of HIV Drug Resistance" (SPRED).
Markowitz M, Mohri H, Mehandru S, et al. Infection with multidrug resistant, dual-trophic HIV-1 and rapid progression to AIDS: a case report. Lancet. 2005;365:1031-1038 . Investigators from Aaron Diamond AIDS Research Center with multiple collaborators (a total of 18 authors) report "the New York City case."
The Case: In brief, a man in his 40s had a negative HIV serology in May 2003, presented with what may be the acute retroviral syndrome in November 2004, had a positive HIV serology in December 2004, and had a CD4+ cell count of 80 cells/mcL by the end of December 2004. Review of the case suggests that HIV had progressed from transmission to symptomatic AIDS in 4-20 months. More information in sequence is provided as follows:
May 9, 2003: HIV seronegative, CD4+ cell count 1500 cells/mL
November 2004: Fever, pharyngitis, fatigue
December 15, 2004: Physician consultation for recurrent fever, pharyngitis, fatigue, HIV seropositive
December 29, 2004: CD4+ cell count 80 cells/mcL, CD8+ cell count 1012 cells/mcL, VL 280,000 copies/mL
January 12, 2005: Pharyngitis, dysphagia, fatigue, weight loss; Detuned HIV serology positive
February 2, 2005: CD4+ cell count 39 cells/mcL, CD8+ cell count 571 cells/mcL
The HIV strain: The viral isolate in this case was dual trophic, multiply resistant, and had a replication capacity of 136%. Further detailed information is provided in the following listing:
Dual trophic with CCR5 and CXCR4
Resistance test results:
Nucleoside reverse transcriptase inhibitors (NRTI): 41L, 67 D/N, 118I, 210L, 215 C/Y, 219E
Nonnucleoside reverse transcriptase inhibitors (NNRTI): 101E, 181I
Protease inhibitors (PI): 10I, 3F, 34Q, 46I, 54M, 63P, 71V, 73S, 77I, 84V, 89V, 90M
Phenotypic sensitivity: efavirenz, delavirdine, enfuvirtide
Subtype: B
Conclusion: The authors conclude that this case represents the convergence of multidrug resistance and rapid progression. In view of the case history, which indicates multiple high-risk sexual contacts, the public health ramifications of the case are particularly important.
Comment: This case was the subject of a special late breaking symposium at the 12th Conference on Retroviruses and Opportunistic Infections (CROI). The following points were emphasized:
How unusual is this rate of progression? A review of the Multicenter AIDS Cohort Study (MACS) experience indicates the likelihood of transmission with progression to AIDS (CD4+ cell count less than 200 cells/mcL) is 7.0 per 10,000 for 6 months and 45 per 10,000 for 12 months. A review of 2,700 seroconverters in the US military showed 15 progressed to AIDS within 1 year. Thus this rate of progression seems extraordinarily rapid considering the estimated time frame of 4-20 months.
How unusual is 3-drug resistance in untreated HIV? The issue of resistance was addressed by Dr. Andrew Brown of the University of Edinburgh, who noted that current trends for resistance tests in patients with acute infections show a general increase in antiretroviral resistance from 1996 to 2000, and then subsequent studies that show a flat pattern or decline in resistance. He also noted that transmission fitness with a single resistance mutation is approximately 20% compared with wild-type virus, and it would presumably be further reduced with 2 or more resistance mutations. Nevertheless, once transmitted, the virologic set-point is essentially the same for drug resistant and drug sensitive strains of HIV. There are occasional reports of 3-class resistance in newly transmitted HIV, but these reports appear to be relatively rare and this finding may reflect to some extent in the reduced transmission fitness associated with resistance mutations. A report from New York City indicates that recent studies show resistance rates for that area have increased to 9.8% for 2003-2004, but that resistance to 3 or more classes is found in less than 1%.
What are the public health implications of this case? This issue was discussed by Harold Jaffe from Oxford who stressed the importance of complete contact tracing (confounded here by the multitude of anonymous partners), a review of the regional experience for other rapid progressors, and a survey of resistance test databases for similar resistance strains as important components of a public health response.
With respect to the follow-up on this case, the New York City Department of Health and Mental Hygiene has issued the following recommendations based on this case: (1) physicians should be alert to the acute retroviral syndrome, obtain an appropriate risk history, and test for both antibody and viral load; and (2) resistance tests should be done for all newly diagnosed HIV infections. Any cases associated with 3-drug resistance should be immediately reported to the Bureau of HIV/AIDS Prevention and Control. (3) Partner names and contact information should be obtained in all patients with HIV infection. This step is especially true with primary HIV infection, which is associated with increased risk of HIV transmission. For further information, see "HIV/AIDS REPORTING AND PARTNER NOTIFICATION."
Derdelinckx I, Van Laethem K, Maes B, et al. Current levels of drug resistance among therapy-naive HIV-infected patients have significant impact on treatment response. J Acquir Immune Defic Syndr. 2004;37:1664-1666 . The authors obtained blood retrospectively from patients who initiated antiretroviral therapy in 2000. Resistance tests were done in specimens obtained within 3 months before initiating highly active antiretroviral therapy (HAART). Virologic failure was defined as the failure to achieve a viral load of less than 50 copies/mL. Of 6 patients with transmitted resistance, only 2 responded. This finding compares with adequate response by 69 of 74 patients who had no detected transmitted resistance ( P = .001). The authors conclude that resistance profile at baseline in chronically infected patients is important in selection of the HAART. They also note that the proper way to do this study would be prospectively and that this strategy is now being carried out in Europe in: "Strategy to Control Spread of HIV Drug Resistance" (SPRED).