•  FEBRUARY/MARCH 2006 HIV JOURNALVIEW

Exclusive, In-Depth Analyses of Recently Published HIV Research
It's one of the Web's most insightful examinations of published HIV research: The Body Pro's HIV JournalView. In our new February/March 2006 issue, David Wohl, M.D., analyzes the significance of:

• a head-to-head comparison of tenofovir + emtricitabine + efavirenz versus zidovudine/lamivudine + efavirenz in treatment-naive patients

• the relationship between adherence and resistance in patients taking NNRTI- versus PI-based regimens

• the successes and limitations of HAART in the developing world

• good news and bad news on investigational enfuvirtide (T-20, Fuzeon) administrations: a needle-free device (cautiously good news) and once-daily dosing (bad news)

When you're through reading this new issue of JournalView, be sure to browse our acclaimed, CME/CE-accredited JournalView issue recapping the most important HIV research developments of 2005.

•  EXPERIMENTAL HIV TREATMENTS

HIV Medications in Development: A Detailed Overview
The past several months have seen a deluge of exciting data on investigational HIV antiretrovirals with significant activity in multidrug-resistant patients. In this exclusive, CME/CE-accredited overview, Edwin DeJesus, M.D., highlights a plethora of important research on these antiretrovirals in development, including data from studies presented at February's 13th Conference on Retroviruses and Opportunistic Infections. Click Here


HIV Gene Therapy Study Seeks to Create Parallel Immune System
A clinical trial now taking place in Los Angeles, San Francisco and Sydney, Australia, has generated a great deal of buzz. The 74-patient, randomized, double-blind, controlled phase 2 trial utilizes genetic engineering and stem-cell science in hopes of spurring the development of a "parallel immune system" in HIV-infected patients, particularly those with significant drug resistance. The study seeks to use stem cells to develop modified blood cells that block HIV infection. In theory, those blood cells would outlast a patient's natural blood cells, effectively creating a stronger, more HIV-resistant immune system and lowering viral load. This exciting strategy is unlikely to replace antiretrovirals, says Ronald Mitsuyasu, M.D., principal investigator at the University of California Los Angeles CARE Center study site. However, the gene therapy could establish "extremely effective control of HIV" when utilized alongside antiretroviral treatment, he said. Preliminary results from the study are not expected until February 2007. Click Here


Development of DFC, an Investigational NRTI, Is Discontinued
The development of an investigational NRTI, DFC (dexelvucitabine, formerly D-D4FC or Reverset), has been discontinued due to concerns that the drug may cause pancreatic inflammation, according to an announcement by Incyte, the company that had been developing the drug. Incyte said that researchers conducting a phase 2b study of DFC found that an "unacceptably high" number of patients -- quantified as "well above ... 10% to 15%" -- developed severe hyperlipasemia when switching to DFC from lamivudine (3TC, Epivir) or emtricitabine (FTC, Emtriva). Click Here

•  HIV ANTIRETROVIRALS & TREATMENT STRATEGIES

Tipranavir Update at CROI 2006
Tipranavir (Aptivus), which was approved by the U.S. Food and Drug Administration in June 2005, represents an important new antiretroviral option for the many HIV-infected patients with multidrug resistance. As with any new antiretroviral, however, there remains much to learn about this protease inhibitor, particularly when it comes to the drug's pharmacokinetics. Gerald Pierone Jr., M.D., takes a look at the latest research on tipranavir that was presented at the 13th Conference on Retroviruses and Opportunistic Infections (CROI 2006). Click Here

Dr. Pierone's article is just one of many exclusive reports from CROI 2006 to be provided by The Body Pro's talented medical faculty. Click here for a full rundown of CROI 2006 highlights!


The Past Becomes the Future: A Revived Role for Monotherapy?
Modern, combination antiretroviral treatment has transformed HIV into a chronic, treatable disease. We have come an awe-inspiringly long way from the earliest years of HIV treatment, when only a single drug was available, and patient morbidity and mortality rates were heartbreakingly high. Yet lately, researchers and clinicians have begun to ponder whether it is time to resurrect the single-drug approach to HIV treatment. Is there really a place for monotherapy in today's HIV therapy landscape? AIDS treatment advocate Bob Huff investigates in this report. Click Here


Possible Interaction Between Addiction Treatment Drug and Atazanavir + Ritonavir
Buprenorphine (Subutex), which is increasingly being utilized as a step-down drug for patients recovering from heroin addiction, may interact with ritonavir (Norvir)-boosted atazanavir (Reyataz), U.S. researchers have found. Physicians in Connecticut have reported three apparent cases of an interaction between these drugs, which has triggered sedative-like adverse events such as grogginess, dizziness and reduced mental function. The case reports were published in the March 21 edition of AIDS. Click Here


FDA Allows Indian Firm to Sell Generic AZT Capsules in U.S.
The U.S. Food and Drug Administration (FDA) granted Indian drug manufacturer Aurobindo Pharma approval to sell and market in the United States a capsule dosage of the generic antiretroviral zidovudine (AZT, Retrovir). The treatment is the first generic capsule form of zidovudine to be approved by the FDA for the U.S. market. The FDA approved generic tablet and oral solution forms of zidovudine for U.S. sale in September 2005, following the expiration of GlaxoSmithKline's patent on the drug. "This is a significant generic approval," Andrew von Eschenbach, acting FDA commissioner, said. "Approval of this additional dosage form of zidovudine should help reduce the cost of this therapy for American patients." Click Here


The Limitations of Antiretroviral Therapy: AETC Slide Presentation (PowerPoint File)
The extraordinarily positive characteristics of today's HIV antiretroviral treatments are clear, but there are nonetheless many drawbacks to therapy -- some of which can become significant limiting factors for some HIV-infected patients. This 49-slide PowerPoint presentation from Marshall J. Glesby, M.D., Ph.D., of Cornell University's Weill Medical College, provides an overview of these limitations, including adherence concerns, the risk of resistance, drug-drug interactions and short- and long-term adverse events. The slides are provided courtesy of the New York/New Jersey AIDS Education and Training Center (AETC). Click Here

•  HIV/HAART-RELATED COMPLICATIONS

Study Finds Racial Differences in Impact of HIV Treatment on Lipids
Race and ethnicity may help predict which HIV-infected patients receiving antiretroviral therapy are at risk for protease inhibitor-related dyslipidemia, according to a cross-sectional analysis by U.S. researchers of data from 626 AIDS Clinical Trials Group studies. The study found that a patient's race or ethnicity had a highly significant impact (P < .001) on triglycerides, HDL cholesterol and non-HDL cholesterol levels while on treatment. Specifically, African-American patients on treatment appeared to have a less-atherogenic lipid profile than white or Hispanic patients on treatment. The study also examined the impact of protease inhibitor-containing regimens on triglycerides: It found that regimens containing ritonavir (Norvir) tended to increase triglycerides for all races/ethnicities, but that regimens not containing ritonavir were associated with a triglyceride increase only in African-American and Hispanic patients. Additionally, researchers noted racial/ethnic differences in the role that Apolipoprotein C-III gene variants may play in the effects of protease inhibitors on plasma lipid levels. Click Here

In this related perspective piece, Patrick Mallon of the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales points out that the ACTG cross-sectional analysis shows just how pivotal it is that researchers conducting pharmacogenetic studies ensure that there is adequate diversity in their patient populations.


Lactic Acidosis: Etiology, Treatment and Recent Research
Lactic acidosis is a rare, but potentially serious, adverse effect that may occur in HIV-infected patients receiving NRTIs, particularly lamivudine (3TC, Epivir), zidovudine (AZT, Retrovir) or the fixed-dose combination NRTIs zidovudine/lamivudine (Combivir) and zidovudine/lamivudine/abacavir (Trizivir). If left untreated, lactic acidosis can cause an array of adverse events, including gastrointestinal complications, liver abnormalities, renal dysfunction and peripheral neuropathy. For an easy-to-digest primer on lactic acidosis, read this fact sheet. Click Here


Experimental Candidiasis Pill May Cut Relapse Rate, Study Suggests
Oral candidiasis continues to be a problem for HIV-infected patients with a low CD4+ cell count. The most common treatments are the antifungal medications fluconazole (Diflucan) and itraconazole (Sporanox), but these medications are now so widely used that concern has grown about the spread of antifungal resistance. A new oral candidiasis treatment, however, may help alleviate those concerns: An international, randomized, single-blind study published in the April 15 issue of Clinical Infectious Diseases has found that an antifungal in development, posaconazole, is as safe and effective as fluconazole through 14 days of treatment -- and may have a lower post-treatment relapse rate. Click Here


U.S. Study Finds Links Between Lipodystrophy and Low Growth Hormone Production
HIV-infected men with lipodystrophy appear to have significantly lower levels of natural growth hormone than HIV-infected women with lipodystrophy, as well as HIV-uninfected individuals, according to the results of a U.S. study published in the April 4 issue of AIDS. The 164-patient study (most of the volunteers were men) also found that white male patients with lipodystrophy appeared to secrete growth hormone at a lower rate than minority male patients with lipodystrophy. Another finding suggested that the success of growth hormone therapy in reversing lipodystrophy may be affected by the patient's waist-to-hip ratio. The findings might help clinicians evaluate the likelihood of specific patients benefiting from growth hormone therapy as a treatment for lipodystrophy. Click Here


Advocacy Groups Charge Schering-Plough With Racial Discrimination for Excluding Blacks From Hepatitis C Trial
Two advocacy groups have charged Schering-Plough with discriminating against African Americans by excluding them from the phase 2 clinical trial of SCH 503034, a hepatitis C drug in development. According to the two advocacy groups, the drug company is barring African Americans -- in whom traditional hepatitis C therapy is less likely to be effective than for white patients -- from participating in the trial in order to produce a more favorable outcome. "The bottom line is that African Americans have been left out of this study to make the drug look good," said Judith Dillard of Community HIV/AIDS Mobilization Project. Bob Consalvo, a Schering-Plough spokesperson, countered that the company consulted with medical experts and decided it was "more prudent and scientific[ally] valid" to restrict African Americans' involvement in the trial until the efficacy of each dose of the drug could be tested. Consalvo said that African-American patients would be involved in a later part of the phase 2 trial. Click Here

•  HIV TESTING

Routine HIV Testing Should Be Implemented Across U.S., Opinion Piece Says
The routine HIV testing bandwagon is taking on more and more passengers: A recent opinion piece by Robert Bazell, NBC News' chief science and health correspondent, called for routine testing to be implemented across the United States. He argues that the "pathetic" application of tests for the virus is a "big reason" that 40,000 U.S. residents contract HIV annually and that 14,000 die from AIDS-related causes. The "biggest obstacle" to increased HIV testing is "inertia" stemming from 1985, when the first HIV tests became available and no effective treatment for HIV existed, Bazell writes. "[I]t is time,” he says, “to realize that AIDS has become another treatable contagious disease, at least in this country, and we can do a lot more to wipe it out." Click Here


Florida Emergency Room to Offer Free HIV Testing to All Patients
South Florida's Jackson Memorial Hospital will now begin offering routine rapid HIV testing to all patients admitted to the hospital's emergency room. South Florida has one of the nation's highest HIV incidence rates; hospital officials hope the initiative will successfully bring more infected patients into treatment and slow the spread of HIV. "Testing is an intervention because you start treating them before they get ill," said Daniel Gurr, M.D., Jackson Memorial Hospital's associate director for emergency services. "But it's also prevention: When someone knows they're positive, they can take steps to protect their spouse, or whoever they are involved with." Between 30 and 50 emergency rooms throughout the United States currently have, or plan to implement, an HIV screening program, according to Richard Rothman, M.D., Research Fellowship Director and Director of Residency Research for the Emergency Department at Johns Hopkins, which was one of the first emergency rooms to implement such a program. Click Here

•  HIV PREVENTION

Tenofovir + Emtricitabine Shows Promise at Preventing HIV; Global Studies Expanded
A regimen of tenofovir (Viread) + emtricitabine (FTC, Emtriva) has proven so effective as a pre-exposure prophylactic in animal studies that the U.S. Centers for Disease Control and Prevention (CDC) announced last week it is expanding ongoing human safety and efficacy trials of the drug combination. In addition to their role in HIV treatment, tenofovir and emtricitabine are also currently used in post-exposure prophylaxis for occupational HIV exposures and in the prevention of mother-to-child HIV transmission. Recently, however, physicians have begun to prescribe the combination as an off-label HIV preventive for patients who admit not using condoms; reports of casual, prophylactic use of the drugs without a prescription are also increasing, leading to concerns about the potential for rising rates of drug resistance. The expanded human trials will allow the addition of a third, as-of-yet-unidentified, U.S. site along with Atlanta and San Francisco, where pre-exposure prophylaxis trials involving only tenofovir are still enrolling HIV-uninfected men who have sex with men. Click Here


Gilead, Health Officials Reluctant to Tout Antiretrovirals as Possible HIV Preventive
Despite the growing scientific interest in the potential for tenofovir (Viread) + emtricitabine (FTC, Emtriva) to prevent HIV infection if taken prior to exposure, Gilead Sciences, Inc., and some health officials are acting to tamp down excitement. The reasons are varied: Gilead reportedly fears that tenofovir + emtricitabine (also marketed as a fixed-dose combination pill, Truvada) will be seen as a "bio-medical condom"; scientists have expressed concern about the potential for increasing rates of resistance; and health officials warn that the drugs should only be administered along with counseling, condoms and regular testing. Click Here

•  HIV POLICY & FUNDING IN THE UNITED STATES

Medicare Nightmare: A Rough Start for the "Part D" Drug Plan
As many U.S. HIV health care providers and pharmacists know all too well, the rollout of the United States' new "Part D" Medicare prescription drug plan has not gone smoothly. Many HIV-infected patients have been mistakenly forced to pay considerably more for their medications than they should, and some have been erroneously barred from receiving medications they previously received without a problem. In this in-depth report, John James of AIDS Treatment News explains what went awry with the Medicare prescription drug plan during its first stumbling weeks. Click Here


U.S. Begins to Use Radio Tracking Tags to Prevent Drug Counterfeiting
The more expensive a drug, the more alluring it is to counterfeiters -- and some HIV antiretrovirals are among the more expensive drugs on the market today. Cases of counterfeit antiretrovirals have popped up in the United States over the past few years, leading the federal government and the pharmaceutical industry to begin fighting drug fraud using modern technology. One method involves putting radio frequency tags on drug packaging -- a strategy that may curb counterfeiting, but has also raised concerns among privacy advocates. John James of AIDS Treatment News provides the details. Click Here

Zidovudine/lamivudine/abacavir (Trizivir) is the first antiretroviral that will be used to test the radio-frequency method of anti-counterfeiting. The fixed-dose combination drug is listed by the National Association of Boards of Pharmacy as one of the 32 drugs most prone to counterfeiting and "diversion," which occurs when a shipment of drugs is stopped before it gets to its destination (usually somewhere in the developing world) and resold elsewhere at higher cost.


ADAPs Nationwide Continue to Suffer; Waiting Lists Persist, Annual Report Finds
As of June 2005, 134,000 HIV-infected people in the United States -- or approximately one out of every four Americans receiving HIV care -- were enrolled in an AIDS Drug Assistance Program (ADAP), but another 800 patients were on waiting lists because their state ADAPs cannot afford to enroll them, according to a comprehensive annual ADAP report from Kaiser Family Foundation and the National Alliance of State and Territorial AIDS Directors. The waiting lists persist despite a 10% increase in the national ADAP budget in 2005. "The need for HIV-related medications continues to outstrip their availability," the report states. If no changes are made to the current ADAP funding system, the report adds, programs "will continue to have to make difficult trade-off decisions between serving more people with less services or serving less people with more services." Click Here

•  HIV NEWS & VIEWS

AIDS Health Care Providers Burning Out From Increased Workloads, Flat Funding, AIDS Research Director Says
Health care workers caring for HIV-infected patients are "burning out" from increased workloads as patients live longer but funding remains stagnant, Michael Saag, M.D., director of the Center for AIDS Research at the University of Alabama-Birmingham, said in an interview on National Public Radio’s "All Things Considered." According to Saag, who was one of the first U.S. physicians to treat HIV-infected patients, nurses and social workers are working longer hours without overtime "out of just a love for what they do and a commitment to the cause." Saag added that a change in the demographics of individuals living with HIV over the past five years -- with many patients now "more disenfranchised from society" -- is contributing to caregiver stress, because cases are more difficult to manage. "I'm concerned about the future of my clinic because I don't know where the next wave of nurses, where the next wave of doctors are going to come from," Saag said. Click Here


HIV Researcher Calls for Continued Push on Harper's Magazine for "Denialist" Article
Harper's Magazine has not sufficiently responded to the HIV community's torrent of criticism following its March 2006 publication of an article that supported the "AIDS denialism" argument, says Dr. John Moore, a noted HIV researcher at Weill Medical College of Cornell University. Many letters of protest were sent to Harper's, including a detailed, point-by-point rebuttal by prominent HIV physicians and advocates. Harper's trimmed the rebuttal to only 250 words, however, and published it only as a letter to the editor, rather than as magazine content. Dr. Moore urges members of the HIV health care community to contact Harper's directly and maintain pressure on the magazine to publish a full rebuttal to the article. This commentary from Dr. Moore explains how you can help. Click Here

•  HIV OUTSIDE THE UNITED STATES

U.S. Focus on Abstinence Is Hurting HIV Prevention Overseas, U.S. Government Report Says
Strict U.S. AIDS funding guidelines dictate that a large proportion of the funding used for HIV prevention in the developing world must be earmarked for programs promoting only abstinence and faithfulness. But these rules are hurting efforts to prevent HIV in developing countries, according to a new report from the U.S. Government Accountability Office. The report warns that many HIV prevention programs overseas are now facing challenges because of the funding rules, including efforts to prevent mother-to-child HIV transmission. AIDS advocate Paul Zeitz, Executive Director of the Global AIDS Alliance, supported the report's findings, saying: "The U.S. approach is far from the 'balanced, effective' policy we were promised by President Bush." Click Here

Newspapers and columnists throughout the United States reacted strongly to the report. "[S]carce resources ought to be focused more clearly on saving lives, not reshaping morality to fit a red-states political agenda," said the Seattle Post-Intelligencer; the Salt Like Tribune said it was "shameful" that HIV continues to spread around the world, while the U.S. government "worries that distributing condoms without preaching abstinence is somehow un-Christian."


WHO's Final "3 by 5" Report Notes Failures and Successes
The World Health Organization (WHO)'s "3 by 5" plan to treat three million HIV-infected patients in the developing world by the end of 2005 managed to reach only 1.3 million, the WHO says in a new report. Although the initiative fell short of its ambitious goals, the WHO notes that the situation in the developing world has dramatically improved since just a couple of years ago, and that the treatment access it provided in 2005 saved between 250,000 and 350,000 lives. Still, only about 17% of HIV-infected children under age 15 in developing countries who urgently needed antiretrovirals were receiving them, and less than 10% of HIV-infected pregnant women were receiving treatment to help prevent vertical transmission of HIV to their babies. Click Here