Between Denial and Hysteria

A hot item made news nationwide early this year: A man in New York City appeared to have been infected with an aggressive strain of HIV previously unseen. Judging by various assessments, we should be somewhere between denial and hysteria. But where? Let's start with three basic questions: Is this HIV uniquely resistant? Is this a novel strain? Is it more aggressive than known strains? Here are the facts we know: While under the influence of crystal meth a 40-something man in New York had multiple sex partners around October. After acute seroconversion symptoms appeared he tested positive for HIV. His T-cell count fell quickly to less than 200, and he was referred to the Aaron Diamond AIDS Research Center for further testing. It is important to note that most experienced HIV clinicians have patients who are resistant to the three major classes of antivirals: nucleosides, nonnucleosides, and protease inhibitors. If this patient was unsafe with multiple partners who were also having unprotected sex with multiple partners, then the chance of contracting a multidrug-resistant HIV strain was fair. So, no, this virus is not uniquely resistant. Studies have shown that up to 25% of newly infected HIV patients are resistant to at least one class of drug. But what is surprising is that detailed analysis of this virus shows that it is not like the multicase drug-resistant viruses we see every day. When special markers are checked, this is a strain of HIV that has not been seen before in other HIV databases. So, yes, this is a novel strain. Since this patient's CD4-cell count fell so quickly, must we assume that this virus is also very aggressive? The answer is both no and yes. As presented at this year's retrovirus conference, at least two large HIV population studies show that some patients who pick up HIV can have CD4 counts fall below 200 and develop AIDS within one year of seroconverting. This probably happens less than 1% of the time, but this news-making virus did not seem to be worse than some others we have seen. However, upon further analysis it might be classed as very aggressive for two reasons: One is that the replicative capacity'a measure of how efficiently the virus multiplies'of this virus is 136%. Wild-type virus, which has no resistance mutations and is found in most untreated HIV patients, is considered the best at replication, and its capacity is set at 100%. When mutations arise to create resistance to antivirals, the efficiency of reproduction is sacrificed. These resistant viruses have a replicative capacity below 100%'sometimes in the 20% range if there are multiple resistance mutations. Thus, it is quite surprising and very disturbing that this drug-resistant virus has a replicative capacity greater than 100%. This patient's virus has also been identified as dual tropic to CCR5 and CXCR4 [see Clinic in February's issue], which means it can use both of these entrance molecules on the surface of CD4 cells to facilitate entry. This happens in only 1% to 2% of HIV cells and allows for rapid CD4-cell destruction. One fact we do not yet know concerns the fitness of the patient, and much of the final analysis of the case will depend on the tests still pending. The patient may not have had the immune competence to mount a reasonable defense against HIV'either by his genetic makeup or from concurrent secondary infections as a result of his extensive sexual activity or exhaustion from crystal meth bingeing. This case may be the result of a tragically unique set of factors causing one weakened man to get very sick very fast with a very strong virus. Ultimately, we do not yet know whether this is an isolated incident or an aggressive new strain of HIV. Until we have more answers, we need to be sure we and our friends continue to practice safer sex. Bowers is board-certified in family practice and is a senior partner with Pacific Oaks Medical Group, one of the nation's largest practices devoted to HIV care, located in Beverly Hills. He has served on the boards of AIDS Research Alliance and Lambda Legal. He is on the editorial board of Postgraduate Medicine.