MARCH 2005
In The News
Number of Reported AIDS Cases Increases in South Florida
For years, South Florida has had a high prevalence of HIV/AIDS. In 2003 (the latest year for which data are available), Florida had the fourth highest rate of AIDS cases per capita compared to all other states and Miami-Dade County had the second highest rate in the nation, behind New York City. Broward and Palm Beach Counties had the fourth and sixth highest rates, respectively. In 2004, new AIDS cases in Florida increased by 24%. Health officials have speculated that this increase is fueled largely by an increase in the number of patients who are unaware that they are HIV-infected until they get sick. AIDS cases in Broward and Miami-Dade counties increased 49% and 33%, respectively, in 2004, as compared to 2003. The only county in Florida in which AIDS cases did not increase in 2004 was Palm Beach County. Despite the significant increase in reported AIDS cases throughout South Florida, health officials hope that the AIDS spike is only a temporary phenomenon, caused by a statewide campaign that has encouraged HIV testing. The campaign that has tested nearly one million people since 2001 has found thousands of people who did not know they were positive, some with AIDS. Encouragingly, new HIV (not AIDS) cases in Florida dropped by 3% in 2004, as compared to 2003.
www.natap.org
HIV Researchers Urge Routine HIV Testing
Of the estimated 950,000 people in the United States infected with HIV, approximately 280,000 are unaware of their HIV status. Current HIV screening methods are inadequate and people are often diagnosed late in their disease. Two studies have independently determined, through the development of computer models, that routine screening for HIV in health care settings is cost effective and may offer survival and CD4 benefits, defined as an increased CD4 cell count at detection, by providing highly active antiretroviral therapy (HAART) to people identified earlier through routine testing. Additionally, routine screening would assist in preventing transmission of HIV. Researchers suggest repeated routine testing every three to five years. The Centers for Disease Control and Prevention (CDC) guidelines currently recommend routine HIV testing wherever the prevalence of HIV infection exceeds 1%, typically in large urban areas and high-risk groups. When assessing the cost effectiveness of screening and incorporating costs and benefits to partners, computer models estimated that one-time screening would cost $194 more than the cost of current practice, while increasing life expectancy by 4.70 quality-adjusted days, for an incremental cost-effectiveness of $15,078 per quality-adjusted life-year. Furthermore, testing when the prevalence of unidentified HIV is as low as 0.5% can still result in a cost effective ratio of less than $50,000 per quality-adjusted life-year, excluding the benefits to partners. A one-time screening was also associated with earlier diagnosis of HIV, and the mean CD4 cell count at detection was 210/mm3 compared to 154/mm3 in the absence of screening. From the models, it was estimated that HIV transmission would drop by 20% and survival would increase by one and a half years with the use of widespread screening. Robert Jansen, director of the Division of HIV/AIDS Prevention at CDC said that, "as a result of these findings, CDC will be reevaluating its HIV screening guidelines over the next two years."
www.natap.org
Hepatitis C Virus (HCV) Associated with Faster HIV Disease Progression
One hundred twenty-six HIV/HCV co-infected injection drug users (IDUs), not receiving treatment for HCV, were assessed to study the effects of HCV genotype on HIV disease progression. HCV genotype was determined using a reverse transcriptase polymerase chain reaction for 104 of the 126 IDUs, and for the remaining 22 subjects, HCV genotype was determined using a line probe assay. Clinical progression was defined as progression to AIDS or pre-AIDS death and immunological progression was defined as a drop in the CD4+ count to 200 x 106 cells/l. The median duration of follow-up was 7.3 years. The distribution of HCV genotypes among the study cohort was as follows: HCV type 1: 48%, HCV type 3: 34%, HCV type 4: 13%, multiple HCV types: 5%. In the pre highly active antiretroviral therapy (HAART) era, IDUs infected with concurrent multiple HCV genotypes showed a significantly elevated risk of clinical progression, compared to IDUs infected with HCV genotype 3 (adjusted hazard ratio [HR] 6.54). When data from the HAART era was included, the risk of clinical progression had an adjusted HR of 3.36 and was not significant. In the pre-HAART era, IDUs infected with multiple HCV genotypes also showed a significantly elevated risk of immunologic progression, compared to IDUs infected with HCV genotype 3 (adjusted HR 4.38). When data from the HAART era was included, the risk of immunologic progression had an adjusted HR of 2.74. Additionally, IDUs infected with genotype 1 had an increased risk of immunologic progression, compared to IDUs infected with HCV genotype 3 (adjusted HR 3.92). Subtype 1a was associated with a higher risk of progression than subtype 1b, when compared to genotype 3, with adjusted HRs of 2.10 and 0.86, respectively. This data suggest that HIV disease progression differs by HCV genotype, and is faster among individuals whose HCV infection involves more than one HCV genotype. The effect of HCV genotype on HIV progression was greater in the pre-HAART era, suggesting that the effectiveness of HAART may diminish the effect of HCV genotype on HIV disease progression.
www.natap.org
CROI Update: Details of the New York Case
On February 11, 2005, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) issued a press release, igniting a flurry of questions and alarm, regarding a NYC resident with a rare strain of 3-drug-class-resistant HIV-1 (3-DCR HIV-1) and rapid progression to AIDS. The patient, a man who has sex with men (MSM), reported crystal methamphetamine use and unprotected anal intercourse with multiple partners.
Twelve days after the initial press release, the 12th Annual Conference on Retroviruses and Opportunistic Infections (CROI), held in Boston, and attended by over 3,000 scientists, included data which revealed the details surrounding the recent New York City case of a, supposedly, "aggressive and untreatable" strain of HIV.
David Ho, of the Aaron Diamond AIDS Research Center, summarized the case and the results of the medical tests the Diamond Center performed. Dr. Ho commented that this isolated case does not indicate that the HIV strain found in this patient is aggressive, as was previously reported, because disease progression is determined not only by the virus, but also by the host's genetic makeup. Dr. Ho confirmed that the patient tested negative for HIV-1 in May 2003. In November 2004, the patient had symptoms of acute retroviral syndrome, including fever and fatigue, and tested positive for HIV-1 by serology on December 16, 2004. The patient was diagnosed with 3-DCR HIV-1 when he presented with a weight loss of 4 kg, continued fatigue, and malaise, in early January 2005. At that time, the patient's CD4 cell count was 80 cells/mm3, which decreased to 28 cells/mm3 in mid-January, and his viral load was 280,000 copies/mL. Although the exact date of the patient's HIV infection is unknown, his progression from HIV-negative in May 2003 to HIV-positive in December 2004 indicates that the maximum amount of time since infection is 20 months. While this relatively short time period of 20 months does indicate an unusually rapid disease progression, similar rapid progressions have been observed before. The Multicenter AIDS Cohort Study (MACS) and the Womens' Interagency Health Study (WIHS) have tracked thousands of HIV-positive and HIV-negative individuals, and have reported cases of rapid progression from HIV to AIDS previously.
The PhenoSense assay was utilized to measure the replicative capacity of this patient's virus, which was found to be 1.38 times greater than wild-type virus. This patient's virus is dual-tropic (can use both CCR5 and CXCR4 co-receptors). Additionally, the diversity within the patient's virus is less than 2% and the patient was found not to possess any genes known to be associated with more rapid HIV disease progression or HLA homozygosity.
Genotypic testing revealed that the patient's virus contained multiple resistance mutations. These mutations were predicted to cause resistance to thymidine analogues, lamivudine (3TC) and emtricitabine (FTC) and reduced susceptibility to abacavir and tenofovir. Most NRTI regimens will likely prove ineffective due to these resistance mutations. Resistance to NNRTIs was also predicted from the presence of mutations Y101E and Y191I, and several protease mutations conferred resistance to PIs. However, a phenotypic analysis of the virus revealed that it is fully susceptible to efavirenz and the fusion inhibitor, enfuvirtide. The patient has started a treatment regimen containing these two antiretrovirals.
Dr. Harold Jaffe, of the University of Oxford, commented "that while this case does highlight the failure of existing HIV prevention strategies for gay men, the case should not be used to scare people. It should be used to remind them of the risks of HIV."
www.nytimes.com
www.natap.org
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