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Rapid, multiresistant HIV in New York City still worrisome
  2005-02-24 (Reuters Health) By Deborah Mitchell
BOSTON (Reuters Health) - In an update of a case first reported two weeks ago involving a gay New York City man with rapidly progressing HIV infection resistant to almost all antiretroviral agents, investigators say they have so far been unable to find any host factor that would account for the rapid disease progression or to match the virus to any previously identified strain.
"The unique feature in this case is the convergence of the two phenomena: the transmission of a remarkably multidrug-resistant HIV-1 variant and the extremely rapid clinical course to AIDS," Dr. David Ho of the Aaron Diamond AIDS Research Center and colleagues in New York, reported here at the 12th Annual Retroviral Conference.
While "additional investigations will reveal whether this is an isolated case or not," the public health implications of this single patient should not be minimized, the researchers stressed. However, they also cautioned that as HIV-1 prevention efforts are reinforced, "care must be taken to avoid punitive measures against the populations most vulnerable to HIV-1."
It is "incontrovertible" that the patient, who is in his late 40s, was infected no longer than 20 months ago with a dual-tropic virus, and he most likely was infected about 4 months before he progressed to AIDS, they report. The patient has a history of extensive unprotected sex and multiple partners, often while using crystal methamphetamine.
Phenotyping and genotyping revealed sensitivity to efurvitide (T-20), but resistance to all three of the other classes of retroviral drugs -- protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside transcriptase inhibitors. Some sensitivity to efavirenz was also seen.
No evidence of a host genetic predisposition to rapid progression has been found. The patient's HLA class I and HLA class II genotypes did not reveal any HLA alleles previously associated with rapid progression. In addition, HLA homozygosity, which is linked with a poor prognosis, was not observed.
The HIV strain has not been linked with any other known variants. Dr. Ho described it as "unique."
A search of the Aaron Diamond AIDS Reseach Center database and the Los Alamos National Laboratory " did not yield a match," according to the team. The virus' gene sequence is currently being compared with those in commercial laboratory databases.
It is a subtype B virus and the patient "clearly has an X4 virus," which is associated with a more aggressive clinical course. Phenotypic studies also show the virus is dual tropic, capable of using both CCR5 and CXCR4 co-receptors.
The patient first presented on December 16, 2004 with pharyngitis and fatigue. He tested positive for HIV at this time, although five tests performed between September 2000 and May 2003 were negative. The patient recalled a 1-week duration of flu-like symptoms in early November about 2 weeks after he had unprotected anal intercourse with multiple partners.
On January 13, 2005, tests confirmed HIV infection, and CD4 counts of 65 cells per microliter and plasma load of 232,000 copies/mL indicated AIDS. Over the past 3 weeks, the patient lost 4 kilograms of body weight.
The presence of multidrug resistance, rapid progression, the patient's history of multiple high-risk sexual encounters, and crystal methamphetamine use prompted New York City health officials to issue the alert to the public and physicians, to begin to trace the patient's sexual contacts and to call for greater HIV prevention vigilance.
The evidence so far leaves many questions unanswered, Dr. Ho said. Does the case represent an agressive HIV-1 stain or a genetic predisposition to rapid progression? Is it single case v. cluster?
He ended by saying, "Given the lack of scientific clarity, we deemed it prudent to notify the NYC Public Health Department." That decision has been questioned, but "We stand by that decision,." He concluded


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