In a special session at the 12th Retrovirus conference, a crowded auditorium of over 2,000 scientists gathered to hear the first public presentation by the doctors who reported it, of the case that has appeared in the media of the man in New York with multi-drug resistant (MDR) HIV who has progressed rapidly to AIDS. The report was recently published in the March 19, 2005 edition of The Lancet, along with an accompanying editorial about the implications of this case in HIV prevention efforts, blasting the Bush administration as being “more interested in imposing its moral view of the world than saving lives, sacrificing others for its ideology instead of doing what’s right.”
Dr. David Ho opened with background information on the single case of a gay male, in his late 40s, who had tested HIV antibody negative prior to May 2003, who then tested positive in mid-December 2004, with a low CD4 cell count of 80 in late December 2004, along with fatigue and weight loss. The man had a history of many sexual contacts, including insertive and receptive unprotected anal sex, and methamphetamine use. Further analysis indicated he was most likely not in the acute (recently infected) stage, and it was estimated that he had probably contracted HIV not less than four but no more than 20 months prior.
Other presenters proceeded to put this case into perspective, using data from several large ongoing cohort studies, including the Multicenter AIDS Cohort Study (MACS) and Women’s Intraagency HIV Study (WIHS), which together have accumulated data on over 10,000 participants over the last 10-20 years.
What is unique about this case is the ability to have evidence for convergence, or meeting, in one patient of: multi-drug resistant HIV; rapid progression to low CD4 count; and the presence of CXCR4, dual-tropic virus (which is typically seen in patients with more advanced disease). What is still undetermined is whether the rapid decline in CD4 cell counts was due to a more virulent (meaning more aggressive, not more infectious) virus, or if the man had a genetic predisposition (inherited likelihood) to rapid disease progression. Also unknown is whether this is a single, isolated case, or because of where this patient happened to be seen it was more quickly recognized.
Various media outlets and the New York City Department of Health have continuously stated that the man is resistant to three classes of drugs.
 However, while resistance tests in this case showed broad resistance to all licensed protease inhibitors (PIs), and multiple resistance to the nukes,
or NRTI class, (although tests show reduced sensitivity to Viread), he showed resistance to only one drug, Viramune, in the non-nukes, or NNRTI class.
He tested sensitive to two other NNRTIs, Sustiva and Rescriptor (meaning he would probably respond well to them) and the entry inhibitor Fuzeon; therefore he was started on a potent 2-class regimen consisting of Sustiva and Fuzeon.
Data from some studies indicate that rapid progression to low CD4 counts and clinical AIDS is not a new phenomenon, but is historically rare. Using a model and data taken from seroconverters (those who had recently contracted HIV within 4.5 months) in the MACS and WIHS cohorts, it was shown that seven out of 10,000 go on to develop AIDS in six months; 45 of 10,000 will develop AIDS in the first year.
Other studies show that while the rate of transmission of drug-resistant virus increased from 1996-2000, it has since stabilized or declined, or even that there has been no increase in transmission of drug-resistant virus at all. However, most of these studies are based on small numbers of individuals.
Furthermore, the viral fitness (ability of the virus to replicate) of drug-resistant HIV in individuals who have been on therapy is generally lower than the normal, wild-type virus that people are usually infected with. Likewise, the transmission fitness, or in other words the ability of the virus to be transmitted, is around 20% for those with HIV who are resistant to only one class of drug, and is even lower for two- or three-class drug-resistant HIV.
In closing, Harold Jaffe, formerly of the U.S. Centers for Disease Control and Prevention, and now with the University of Oxford Department of Public Health, UK, posed the question, Why are some people still putting themselves at risk for infection more than two decades into the epidemic? Factors that he suggested contribute to high-risk behavior include:
 • Prevention fatigue—older gay men have been hearing prevention messages for 20 years
• Failure to reach more marginalized MSM, particularly Blacks and Hispanics
• Viral load beliefs—the belief that if an individual has an undetectable viral load, transmission can’t occur
• Substance abuse leading to unsafe sex and disinhibition
• Increasing use of the internet to have anonymous sex
• Lack of fear—people no longer fear HIV since it has become to many a treatable disease
In conclusion, Jaffe stated, “If lack of fear has become a driver of the epidemic, should we use cases such as this to scare people at risk? I personally don’t think so, but at the same time I think it is important to remind people what we’re dealing with. The American epidemic is not over. Each year about 40,000 people in this country develop AIDS, and last year approximately 18,000 died. The cumulative death toll from the epidemic exceeds all the deaths on the battlefield in all the wars that this country fought in the last century. And although tremendous advances have been made in therapy, it isn’t curative, it requires a high degree of adherence, and there are significant short and long term toxicities, not all of which we entirely understand. As therapy becomes more widely available, I think we should anticipate that drug-resistant HIV will spread, just as would be the case for other infectious diseases. So unless we can improve our prevention strategies, work with leaders and organizations in the at-risk communities, and do a better job of communicating with those who are truly at high risk, I’m afraid that we may be having sessions like this for years to come.”
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