•  HIV TREATMENT & COMPLICATIONS

Traditional Risk Factors, not HAART, Drive Development of Metabolic Syndrome, Study Suggests
HAART has often been considered the likely suspect for increasing the risk of metabolic syndrome in HIV-infected individuals. However, new study results published in the March 1 issue of Clinical Infectious Diseases reveal that traditional cardiovascular risk factors may shoulder the bulk of the blame. The prospective, cross-sectional study of 471 HIV-infected individuals in a U.S. urban outpatient clinic revealed that the overall prevalence of metabolic syndrome was approximately 25% for both the HIV-infected participants and a group of matched, HIV-uninfected controls. The 10-year risk of myocardial infarction was also similar for the two populations. Interestingly, dyslipidemia was more common among the HIV-infected cohort versus the HIV-uninfected cohort, despite the greater use of lipid-lowering therapy among the former. Neither the type nor the length of HAART was found to predict the occurrence of metabolic syndrome. The investigators stated, “These findings, along with a lack of independent effects of HAART on metabolic syndrome, support the notion that ... traditional risk factors (i.e., hypertension, hyperglycemia, and obesity) may be more important than HAART-related factors for the prediction of metabolic syndrome and cardiovascular disease risk” among HIV-infected individuals. Click Here

In an accompanying editorial, Clara Jones of Tufts University Medical School stresses that, although the prevalence of metabolic syndrome was nearly identical for the HIV-infected and uninfected cohorts, the findings do “not controvert the evidence that metabolic complications increase in persons after initiating HAART.” Several individual components that lead to the development of metabolic syndrome differed significantly between the two populations, she writes. Most notably, HIV-infected patients had significantly lower high-density lipoprotein cholesterol levels and significantly higher triglyceride levels than uninfected individuals. Jones concluded that “the findings do not diminish the potential importance of addressing the risk factors in individual patients to decrease the risk of cardiovascular disease or type II diabetes.”


FDA Panel to Consider CCR5 Antagonist Maraviroc in April
The safety and efficacy of the CCR5 antagonist maraviroc are scheduled for review by an advisory panel of the U.S. Food and Drug Administration (FDA) on April 24. The data of interest come from trials in which maraviroc was administered twice daily to treatment-experienced patients with drug-resistant HIV. If approved, the agent will be the first CCR5 antagonist included in clinicians’ armamentarium for HIV. Pfizer, Inc., which is developing maraviroc, plans to market the drug along with a coreceptor tropism assay made by Monogram Biosciences, Inc., that evaluates whether patients are likely to respond to the treatment. While Pfizer reports that trials of maraviroc have thus far gone smoothly, rival drug companies have hit major stumbling blocks while developing their own CCR5 antagonists. UK-based GlaxoSmithKline stopped development of its candidate aplaviroc (GSK873140) in 2005 after some patients developed signs of liver damage. At Schering-Plough Corporation, mid-stage trials of its second-line candidate are continuing despite reports of the development of lymphoma in some patients. Click Here


Side-Effect Warnings Issued for Enfuvirtide Biojector Users
Biojector 2000, a needle-free, carbon dioxide-powered device currently being tested for use with enfuvirtide (T-20, Fuzeon) in clinical trials, has generated excitement among both patients and providers due to an observed reduction in enfuvirtide injection-site reactions. Unfortunately, it appears that Biojector can cause its own family of adverse effects, particularly for patients who have blood-clotting disorders or who are taking anticoagulants. These adverse effects can include long-lasting nerve pain, bruising and broken blood vessels, according to recent changes to enfuvirtide’s product labeling. The new labeling urges patients who use Biojector to inject enfuvirtide into their upper arm, abdomen (but away from the naval) or the front part of their thigh, where adverse effects are less likely to occur. Click Here


Efavirenz Labeling Updated With Drug-Drug Interaction Information
The efavirenz (Sustiva, Stocrin) package insert has been updated to include new information on the pharmacokinetic interactions between efavirenz and several other medications. The insert specifically warns against administering efavirenz concurrently with several drugs, including bepridil (Vascor), a calcium-channel blocker; voriconazole (Vfend), an antifungal drug; or pimozide (Orap), an antipsychotic medication used to treat Tourette's disorder. Other drugs identified as having the potential to cause significant interactions with efavirenz include the antimycobacterial rifampin (Rifadin, Rimactane), calcium-channel blockers such as diltiazem (Cardizem, Cartia, Dilacor, Diltia, Tiazac), and the antifungals itraconazole (Sporanox) and ketoconazole (Nizoral). Click Here


Scientists Find Interleukin 7 Helps Staunch T-Cell Depletion Ex Vivo
Researchers at the U.S. National Institutes of Health (NIH) may have uncovered a new strategy for preventing the immune-cell depletion caused by HIV infection. Paolo Lusso and colleagues at NIH's National Institute of Allergy and Infectious Diseases found that the addition of interleukin 7 (IL-7) to CD4+ and CD8+ T cells isolated from 24 HIV-infected patients dramatically reduced the number of cells that underwent HIV-induced apoptosis. IL-7 was more effective at blocking cellular suicide when fewer immune cells were present, indicating better effects in patients with more advanced disease. IL-7 has long been known to be essential for producing and maintaining T-cell populations in individuals; the findings from this study suggest that, when combined with antiretroviral therapy, the administration of IL-7 may be effective for helping stem HIV's assault on T cells. The next step is to test the immune-preservation effects of supplemental IL-7 in monkeys infected with simian immunodeficiency virus before proceeding to human studies. The study was published Feb. 6 in an early online edition of the Proceedings of the National Academy of Sciences. Click Here

•  HIV TRANSMISSION & TESTING

New HIV Protein Discovery May Profoundly Impact Vaccine Development
U.S. researchers have identified an antibody that can block the binding of HIV to CD4+ cells in a way that HIV may not be able to adapt to -- a finding that may dramatically affect the development of an effective HIV vaccine. Led by a team at the U.S. National Institute of Allergy and Infectious Diseases (NIAID), the researchers found that an antibody known as b12 binds to a key HIV protein, gp120, at the exact point where gp120 initially attaches to a CD4+ cell. Since gp120 does not change shape until after it attaches to a CD4+ cell, the researchers believe it is a stable place to attack -- thus making it an ideal target for HIV vaccines. "This elegant work ... provides us with a long-sought picture of the precise interaction between the HIV gp120 surface protein and this neutralizing antibody," said NIAID Director Anthony Fauci, M.D., in a news release. "This finding could help in the development of an HIV vaccine capable of eliciting a robust antibody response." The research was published in the Feb. 15 issue of Nature. Click Here


Macrophages in Testicles a Rich Reservoir for HIV, Researchers Find
HIV-infected men on antiretroviral therapy sometimes have detectable HIV-1 RNA in their semen, even though their plasma viral load is undetectable. A new study by French scientists may help explain this phenomenon: Published in the December 2006 issue of the American Journal of Pathology, the study found that macrophages present in testicular tissue possess all of the receptors -- CD4, CXCR4, CCR5 and DC-SIGN -- to which HIV can bind. These cells were found to be highly susceptible to HIV infection and served as reservoirs for HIV replication. Further study, the researchers hope, might lead to drugs that can help prevent HIV transmission by suppressing HIV replication in the testes. Click Here


Cluster of Drug-Resistant HIV Reported in Washington State
A small outbreak of drug-resistant HIV occurring in four men in King County, Washington, has local health officials concerned about the risk of wider transmission. The HIV strain is resistant to at least two antiretroviral drug classes and has partial resistance to a third. All four men were tested for HIV within a 15-month window and were found to be infected with the same genetic strain. None of the men were known to have had sex with one another; each also reported methamphetamine use and multiple anonymous sexual partners, including men. Some of the men's partners have been identified, and to date none have tested positive for the resistant strain. Public health officials have heightened HIV drug resistance monitoring in the area to track the possible spread of this strain, and are targeting gay bars and bathhouses to provide information about the strain along with safe-sex reminders. Click Here


Largest HIV Vaccine Trial to Date Set to Launch in South Africa
A large-scale, double-blind, controlled, phase 2b trial will soon begin in South Africa to test the most promising HIV vaccine to date: Merck’s MRKAd5 HIV-1 vaccine. The primary goal of the trial, led by researchers from the United States and South Africa and supported by the U.S. National Institute of Allergy and Infectious Diseases, will be to determine whether the vaccine can prevent HIV transmission or lower HIV RNA levels in people who subsequently contract the virus. The study population will include 3,000 healthy, sexually active, HIV-uninfected men and women between the ages of 18 and 35. Half will receive the vaccine, and half will receive a placebo. At the end of four years, infection rates between the two groups will be compared. This trial will help address the efficacy of the vaccine in a heterosexual population, as well as its efficacy in women. Researchers also hope to determine whether the vaccine, which is based on the B strain of HIV, is effective against the C strain of the virus -- the prevalent strain in South Africa. If this trial is a success, a phase 3 trial involving at least 10,000 individuals could begin in three to five years. Click Here


Japan's HIV Incidence Hit Record High in 2006
A record 914 new HIV cases were reported in Japan in 2006 -- an 8.8% increase from 2005, according to the Japanese Foundation for AIDS Prevention. The most common transmission route appears to be sex between men, which may explain why men outnumbered women 15 to 1 in terms of new infections. Although Japan's HIV caseload remains low by global standards, the upward trend in transmission stands in stark contrast with most other developed nations, where the incidence of HIV infection is decreasing and most new cases involve heterosexuals. Click Here

•  HIV/HEPATITIS C COINFECTION

New Findings Support Protective Effect of HIV/HCV Coinfection on Lipids
Coinfection with HIV and hepatitis C virus (HCV) is typically a double whammy for newly diagnosed individuals, but new findings from researchers at the University of Texas South-Western Medical Center at Dallas highlight one positive aspect of coinfection. After performing a retrospective analysis of 359 HIV-infected individuals, 25% of whom were coinfected with HCV, the researchers found that far fewer coinfected individuals had elevated total cholesterol and triglyceride levels compared with individuals who were infected with HIV alone. Coinfected individuals also had significantly lower low-density lipoprotein cholesterol and higher high-density lipoprotein cholesterol levels than HIV-monoinfected patients. Moreover, the risk of hypercholesterolemia was 63% lower for coinfected individuals after adjusting for duration of therapy, race, aminotransferase levels and platelet count; the risk of any dyslipidemia was 47% lower after adjusting for these factors. As stated in their November 2006 HIV Medicine article, the investigators believe that these findings “significantly strengthen the hypothesis of an apparent protective effect of hepatitis C virus infection on the development of dyslipidaemia.” Click Here