5 Questions: Shafer on new HIV strain
An occasional feature in which a medical expert answers five questions on a science or policy topic of interest to the Stanford community
1. Is it rare for viruses with drug resistance to be spread from one person to another?
Shafer: In the United States and Europe, 10 to 15 percent of new HIV-1 infections are caused by viruses that already have some degree of drug resistance (primary drug resistance). Because drug resistance does not develop naturally (i.e. in the absence of drug therapy), primary drug resistance occurs only when viruses that develop resistance in one person are spread to another person. Most transmitted drug-resistant strains are resistant to one or two of the three major drug classes. About 1 percent is resistant to all three drug classes.
2. In the New York case, drug resistance is only part of the problem. The other significant thing is that the man developed full-blown AIDS within weeks of exposure. How does this compare with the usual time to development for AIDS?
Shafer: In the absence of antiretroviral drugs, the median time from infection to advanced immunosuppression or AIDS is about nine years. However some patients progress to AIDS within several months while others take more than 20 years.
3. Can you explain why this new strain is attracting so much attention?
Shafer: As noted above, primary infection with highly multidrug-resistant viruses is uncommon, occurring in about 1 percent of new infections, and rapid progression to AIDS is also uncommon. Therefore, the combination is extremely rare. In addition, drug-resistant viruses are usually less virulent than wild-type viruses and most scientists would expect drug-resistant viruses—especially those that are highly resistant—to damage the immune system more slowly than wild-type viruses.
4. Is this bug going to change the course of the AIDS epidemic in the United States?
Shafer: The course of the HIV epidemic in the United States is determined primarily by behavioral changes that affect HIV transmission. Therefore, this case could serve as a wake-up call to re-emphasize the need for reducing high-risk behaviors and for increasing testing for HIV as recommended this week in a study published by Doug Owens' group. The New York patient engaged in many high-risk behaviors; there is no evidence that the HIV strain he was infected with spreads differently from other HIV strains.
However, it is essential to study this virus in the laboratory to understand why it was able to cause disease so rapidly, defying the conventional wisdom that drug-resistant variants are usually less virulent than wild-type variants. In other words, is this virus what some reporters have been calling a "superbug"—one that is highly drug resistant and highly virulent.
HIV mutates at an extraordinarily high rate and there is tremendous diversity among circulating viruses throughout the world. Nonetheless, nearly every study that has examined why some people progress to AIDS rapidly and others slowly, has found paradoxically that it is not the genetic makeup of the virus that influences disease progression but rather the genetic make-up of the infected person. Indeed, variation at more than 10 different human genes has been shown to influence disease progression. Therefore, I suspect, and hope, that we are not witnessing the emergence of a "superbug", but rather a combination of two uncommon unfortunate events: the transmission of a highly drug-resistant virus to a highly susceptible individual.
5. Have scientists been tracking the rise of drug-resistant HIV viruses?
Shafer: Our laboratory maintains a publicly available on-line database(http://hivdb.stanford.edu) that catalogs the genetic mechanisms of HIV resistance and links these mechanisms to patient treatments and clinical outcome. It's used by clinicians who are treating patients with drug-resistant infections and by scientists developing new HIV drugs. We also have a five-year contract with the CDC to test viruses from newly diagnosed patients for the presence of primary drug resistance.