Transmission of Highly Resistant HIV
September 30, 1998
Transmission of Highly Resistant HIV
ABSTRACT & COMMENTARY
Synopsis: Transmission of multi-drug resistant HIV-1 is documented.
Source: Hecht FM, et al. N Engl J Med 1998;339:307-311.
Four days after having unprotected receptive anal intercourse with an HIV-positive partner, which was apparently aborted before ejaculation (so to be "safe"), a man previously known to be HIV-negative developed symptoms of primary HIV infection. His seropositive partner had received multiple antiretroviral agents with which he was poorly compliant. Analysis showed that virus from both men had nearly identical genotypes with multiple mutations conferring resistance to zidovudine, lamivudine, and all four commercially available protease inhibitors (PI). Phenotypic analysis confirmed at least two-fold to 12-fold elevations in the IC50s to these agents.
COMMENT BY CAROL A. KEMPER, MD
This report of the first documented case of sexual transmission of multiply drug-resistant HIV-1 virus came as no surprise to those of us attending the 12th International Conference on AIDS in Geneva in June. After all, transmission of zidovudine-resistant HIV has been reported, as has apparent "de novo" resistance to zidovudine and lamivudine in treatment-naïve patients. My colleagues at Stanford University recently provided genotypic evidence of multiple drug resistance mutants in up to 40% of heavily pre-treated patients in the San Francisco Bay Area.1 Even in those with successful suppression of plasma viral load replication competent virus can persist in certain cells for at least two years.
Additional genotypic evidence for transmission of drug-resistant variants was provided by both Swiss and German investigators at the conference. Of 67 individuals presenting with primary HIV infection in Geneva, 7.5% had resistance to zidovudine, 1% to nevirapine, and 10.5% had major resistance to PI (Abstract 32280). A high prevalence of resistance to PI was found in 17 of 27 (63%) treatment-naïve patients in Berlin (Abstract 412080).
These cases should urgently compel us to rethink our public policy and community response toward this disease. Despite all of the apparent benefits and overall improvement in survival with recent advances in therapy, broad resistance to antiretroviral drugs is occurring at an alarming rate. If we dealt with this disease like any other communicable infection, we'd overcome our contemporary prudishness and approach public education and prevention in a straightforward and effective manner, we'd redouble our focus on vaccine development, and public health dollars would be directed at improved identification of newly infected people, better surveillance for drug resistance, and directly observed therapies with public health intervention to prevent further spread of this disease. (Dr. Kemper is in the Division of Infectious Diseases, Santa Clara Valley Medical Center.)
Reference
1. Shafer RW, et al. Multiple concurrent reverse transcriptase and protease mutations and multidrug resistance of HIV-1 isolates from heavily treated patients. Ann Intern Med 1998;128:906-911.
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