February 26, 2007
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The EXPLORE study examined the effectiveness of a behavioral regimen to prevent HIV acquisition among men who have sex with men from six major cities in the United States. All the subjects enrolled in the study were HIV negative and were followed every six months for seroconversion.
In the context of that study, which was completed a while ago, seroconversion was documented in 259 men. Of those, we were able to acquire samples, either from the date of documented seroconversion or shortly thereafter, and characterize the viruses by genotyping in 259 men. In the end, 159 had genotyping results.
We used those [results] to look at the prevalence of drug resistance in these recently infected men, and we found overall that 15.9 percent of the men, or 31 men in the group, had resistance to at least one [HIV] drug in any class. Most had resistance to NNRTIs [non-nucleoside reverse transcriptase inhibitors], but we also saw NRTI [nucleoside analog reverse transcriptase inhibitor] and PI [protease inhibitor] resistance. Seven men in the group had multi-class -- two or three class -- [HIV] drug resistance.
We went on to check the HIV subtypes of those recently transmitted viruses, and they were all subtype B. Then we went on to determine the tropism, the X4 [CXCR4] coreceptor usage, in those strains, because of a recent report from a year or so ago of a man in New York who was infected with a multidrug-resistant strain that was also X4 tropic and rapid progressing. We wanted to see if any of the men in this cohort had X4-using strains. Of the group, we had 126 men who had tropism results, and four, or just over 3.3 percent of those men, had strains that were able to use the CXCR4 coreceptor. One of those four men who had an X4-using strain had NNRTI resistance. None of the men with multi-class resistance had X4-using strains.
This study will be published in AIDS. It's in press there, with the study details.
Were there any surprises?
No, I don't think so. The patterns of resistance that we saw were not unexpected. One unusual thing about this study was that, because the EXPLORE study itself, the main study from which the samples were obtained, was a study of a behavioral intervention, we had quite a lot of detailed information on the risk factors -- sexual and drug use-related risk factors -- among the men in this cohort. We were able to look for associations of resistance with a whole variety of activities.
We didn't find, in this study, any strong associations, though it may be that, in the end, [that was because] we were only looking at 195 men. We may not have the power of a very large epidemiologic study, but we were able to look at a large variety of risk factors to see if they were associated with resistance.
What kind of risk factors?
Details on drug and alcohol use, details on sexual practice that might relate to risk factors.
Where were the study sites?
The study sites were Boston, Chicago, Denver, New York, San Francisco, and Seattle -- those six major cities.
Are there theories about why NNRTI resistance is more prevalent than NRTI resistance?
No. What you don't know from a study of this type is whether the NNRTI resistance was more prevalent in the primary source, [the people] who infected these men; or whether there's any kind of an advantage of those strains for transmission; or if simply those mutations associated with NNRTI resistance are well tolerated by the virus and linger longer after the time of infection and therefore would be more readily detected as much as six months after the infection occurred. You don't know if you're seeing something related to viral fitness or [if] it has to do with the prevalence of [resistant virus in] the populations infecting these men. But this is what you detect when you are able to look within six months of infection in a cohort like this.
Was the data broken down by race?
The [published] article will detail the racial breakdown in the study. We didn't find any associations with race. But again, some studies have. This study only included 195 men, so it may have been underpowered for those kinds of analyses.
What percentage was non-white?
I don't recall.
Thank you very much for taking the time to talk to me.
To view study abstract, click here.
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