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    <recommendedItem id="20100101_19_344"
                     title="FDA Revises HIV Drug Label for Liver Complication"
                     score="0.011"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18229?impressionId=1265747274396"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has updated labels of the HIV drug didanosine (Videx and Videx EC) to include warnings for potentially serious liver damage.&lt;/p&gt;
&lt;p&gt;Although these cases are rare, the drug may cause noncirrhotic hypertension in patients, a potentially fatal complication which the FDA discovered through 42 postmarket, adverse event reports.&lt;/p&gt;
&lt;p&gt;Of those patients, three required liver transplant and four died. Two deaths were caused by esophageal hemorrhage, while two more were caused by progressive liver failure.&lt;/p&gt;
&lt;p&gt;One patient suffered multiorgan failure, cerebral hemorrhage, sepsis, and lactic acidosis.&lt;/p&gt;
&lt;p&gt;The FDA said in a statement that it chose not to recall the drug because it believes its benefits outweigh potential risks, but advised that treatment decisions be made on an individual basis between healthcare professionals and patients.&lt;/p&gt;
&lt;p&gt;The agency added that causal association is difficult to determine in postmarket reports, but that alternative causes of the hypertension were ruled out in well-documented cases.&lt;/p&gt;
&lt;p&gt;Healthcare professionals who determine didanosine is effective in treating a patient should monitor that patient for the development of portal hypertension and esophageal varices, the agency said.&lt;/p&gt;
&lt;p&gt;Didanosine is used in combination with other HIV medications to help maintain CD4 cells in patients.&lt;/p&gt;
&lt;p&gt;The drug already has a black box warning for lactic acidosis and hepatomegaly with steatosis.&lt;/p&gt;
&lt;p&gt;Like the antiretroviral agents hydroxyurea and ribavirin, didanosine has been associated with the development of liver toxicity.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_217"
                     title="Herpes Therapy Doesn&apos;t Bar HIV Transmission (CME/CE)"
                     score="-0"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/18071?impressionId=1265747274396"
                     
      &lt;p&gt;Treating herpes has no effect on the transmission of HIV among discordant couples, researchers said.&lt;/p&gt;
&lt;p&gt;The lack of efficacy was found in a large, randomized clinical trial despite significant reductions in HIV viral load among those treated for herpes simplex-2 (HSV-2), according to Connie Celum, MD, of the University of Washington, and colleagues.&lt;/p&gt;
&lt;p&gt;Researchers will have to look for new ways to prevent transmission among discordant couples (in which one partner has HIV and the other does not), Celum and colleagues concluded online in the&lt;em&gt; New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The study comes after earlier trials also showed that treating HSV-2 with the antiviral acyclovir (Zovirax) did not lower the risk of getting HIV. (See &lt;a href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; mce_href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; target=&quot;_blank&quot;&gt;Herpes Treatment No Help in Preventing HIV&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The trials  --  and the current study  --  had their origins in epidemiological and laboratory observations that having an HSV-2 infection increased the risk of contracting HIV.&lt;/p&gt;
&lt;p&gt;Researchers reasoned that a converse effect might also be true  --  treating HSV-2 in HIV-negative people might reduce their risk of infection.&lt;/p&gt;
&lt;p&gt;The reasoning was bolstered by clinical trials showing that treating HSV-2 in HIV-positive people lowered their viral load.&lt;/p&gt;
&lt;p&gt;In the current study, that effect also occurred. HIV-positive volunteers treated with acyclovir saw, on average, a reduction in plasma concentration of HIV by 0.25 log&lt;sub&gt;10&lt;/sub&gt; copies per milliliter compared with members of the placebo group. The difference was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;But transmission among the couples was not affected, implying that a greater reduction in viral load is needed, the researchers said.&lt;/p&gt;
&lt;p&gt;The study, randomized and placebo-controlled, included 3,408 couples in Africa in which only one of the partners had HIV (but was not taking antiretroviral therapy) and also had an HSV-2 infection.&lt;/p&gt;
&lt;p&gt;The outcome was first reported at the Cape Town meeting of the International AIDS Society last year (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; target=&quot;_blank&quot;&gt;IAS: Acyclovir Flops in Preventing HIV Transmission&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The primary outcome was transmission between partners, verified by genetic sequencing of the virus.&lt;/p&gt;
&lt;p&gt;Transmission between partners was verified in 84 of the 132 recorded cases of transmission, the researchers said, and they were evenly divided  --  41 among those getting the drug and 43 in the placebo group.&lt;/p&gt;
&lt;p&gt;On the other hand, the use of the drug reduced the occurrence of herpes lesions by 73%, which was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;The reduction of herpes lesions suggests that the drug was being used, the researchers said, and therefore that the lack of efficacy against HIV was not a result of nonadherence to acyclovir.&lt;/p&gt;
&lt;p&gt;Overall, the rate of HIV transmission in the study was 2.7 cases per 100 person-years, markedly lower than earlier observations. The researchers attributed that to such interventions as monthly counseling on risk reduction and free condoms.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study had support from the Bill and Melinda Gates Foundation, as well as the University of Washington, the National Institute of Allergy and Infectious Diseases, Gen-Probe, and the National Institute of Mental Health.&lt;/p&gt;&lt;p&gt;Celum reported financial links with GlaxoSmithKline and several other authors reported links with various pharamceutical companies.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_205"
                     title="Slim Evidence for Effect of Home Care on HIV Treatment (CME/CE)"
                     score="-0.001"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/18037?impressionId=1265747274396"
                     
      &lt;p&gt;Home-based care can improve some aspects of HIV treatment, according to a systematic review of reported studies.&lt;/p&gt;
&lt;p&gt;But the evidence is slim, and no studies looked at how home-based care affects AIDS progression or death, according to Taryn Young, MBChB, of the Medical Research Council of South Africa, and Karishma Busgeeth of the Council for Scientific and Industrial Research in Pretoria, South Africa.&lt;/p&gt;
&lt;p&gt;In addition, few of the studies evaluated home-based care in developing countries, where it is being considered to alleviate pressure on hospitals, the researchers noted in a &lt;em&gt;Cochrane Systematic Review&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Home-based care is aimed at improving quality of life and reducing the need for hospital care, &quot;especially where public health services are overburdened,&quot; the researchers wrote in the review.&lt;/p&gt;
&lt;p&gt;But there has been no systematic evaluation of home-based care in the setting of HIV/AIDS, they said.&lt;/p&gt;
&lt;p&gt;To help fill the gap, they found 13 published reports, referring to 11 randomized clinical trials, as well as two such trials currently under way.&lt;/p&gt;
&lt;p&gt;Of the 11 studies with published reports, 10 randomized individuals and one (in Uganda, the only one conducted in Africa) randomized households.&lt;/p&gt;
&lt;p&gt;The studies looked at a range of interventions: &lt;ul&gt; &lt;li&gt;Three studies evaluated home-based intensive nursing versus standard care for effects on patient knowledge of HIV and related medication, adherence, viral load, and CD4 counts.&lt;/li&gt; &lt;li&gt;Two studies compared a transprofessional team versus an independent primary care nurse. One looked at quality of life and survival and the other at the time patients spent in the program, as well as cost.&lt;/li&gt; &lt;li&gt;Two studies compared the effect of computer-based education versus brochures, nothing, or standard medical care on such outcomes as perceived social isolation, decision-making confidence, health status, quality of life, risk behaviors, and health service utilization.&lt;/li&gt; &lt;li&gt;Two studies looked at exercise.&lt;/li&gt; &lt;li&gt;One study looked at two months of home total parenteral nutrition versus dietary counseling.&lt;/li&gt; &lt;li&gt;One study of diarrhea compared home-based water chlorination, safe storage, and education with education alone.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers reported that intensive home-based nursing significantly improved self-reported knowledge of HIV and medications, self-reported adherence, and differences in pharmacy drug refills.&lt;/p&gt;
&lt;p&gt;Another study, which looked at the proportion of participants with greater than 90% adherence, found statistically significant differences over time with home-based nursing. But that study found no significant change in CD4 counts and viral loads.&lt;/p&gt;
&lt;p&gt;The third such study found significant differences in HIV stigma, worry, and physical functioning but no differences in depressive symptoms, mood, general health, and overall functioning.&lt;/p&gt;
&lt;p&gt;The studies comparing comprehensive case management by transprofessional teams compared to usual care by primary care nurses showed no effect.&lt;/p&gt;
&lt;p&gt;The study comparing home total parenteral nutrition and dietary counseling found no significant impact on overall survival and rate of readmission to hospital.&lt;/p&gt;
&lt;p&gt;The two computer-based studies found no effect on health status and decision-making confidence and skill, but did find a reduction in social isolation after controlling for depression.&lt;/p&gt;
&lt;p&gt;The two trials evaluating home exercise programs found conflicting results.&lt;/p&gt;
&lt;p&gt;And the home-based safe water systems reduced diarrhea frequency and severity among persons with HIV in Africa, the researchers reported.&lt;/p&gt;
&lt;p&gt;In general, the researchers concluded that there were few studies; study populations tended to be small; and the studies did not address the effect of home-based care on important medical endpoints, such as mortality.&lt;/p&gt;
&lt;p&gt;&quot;Further large studies should therefore focus on evaluating these significant endpoints, on feasible interventions for developing countries, and on how home-based care fits into the current treatment context,&quot; they concluded.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;There was no external support for the study. The researchers reported no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_141"
                     title="HIV Drug Resistance Set to Rise? (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/17962?impressionId=1265747274396"
                     
      After leveling off for several years, resistance to HIV drugs is likely to rise again, if the conclusions of a new mathematical model turn out to be accurate.&lt;br&gt;
&lt;br&gt;The model suggests that about 60% of the resistant HIV strains now circulating in San Francisco are capable of starting their own mini-epidemics, according to Sally Blower, PhD, of UCLA, and colleagues.&lt;br&gt;
&lt;br&gt;In an online article in &lt;em&gt;Science&lt;/em&gt;, the researchers warn that a new wave of drug-resistant HIV strains could interrupt progress toward controlling the pandemic around the world.&lt;br&gt;
&lt;br&gt;Early modeling by her group  --  later borne out by data  --  suggested that HIV resistance would emerge among patients on treatment and then plateau, Blower told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;But the new model suggests that some resistant strains are now being transmitted among people who have never been treated. &quot;Essentially, it&apos;s like the beginning of the HIV epidemic all over again,&quot; Blower said.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;The study drew a mixed reaction from HIV/AIDS specialists.&lt;/p&gt;
&lt;p&gt;Resistance expert Mark Wainberg, PhD, of McGill University in Montreal, one of the discoverers of the HIV drug 3TC, called the article &quot;very important.&quot;&lt;/p&gt;
&lt;p&gt;In an e-mail to &lt;em&gt;MedPage Today&lt;/em&gt;, Wainberg, one of the discoverers of the HIV drug 3TC, said, &quot;The fact that transmission of drug resistance represents a major concern for the future ... is terribly disconcerting.&quot;&lt;/p&gt;
&lt;p&gt;But not everyone is disconcerted. The fears raised by the study are &quot;hype,&quot; according to John Mellors, MD, of the University of Pittsburgh, because the researchers assume that HIV therapy is unchanging.&lt;/p&gt;
&lt;p&gt;&quot;In fact, therapy is continually changing and is become more effective and generating less resistance,&quot; Mellors wrote in an e-mail. &quot;So the sky is not falling.&quot;&lt;/p&gt;
&lt;p&gt;Blower and colleagues noted in &lt;em&gt;Science &lt;/em&gt;that many models of resistance only track the effects of single strains, but the new model is capable of analyzing multiple strains with different levels and types of resistance  --  including single-, double-, and triple-class resistance to the three major HIV drug classes.&lt;/p&gt;
&lt;p&gt;When tested retrospectively, they said, the model reproduced the resistance dynamics that were seen in San Francisco as treatment developed from monotherapy, through dual therapy, to the early triple-drug cocktails and to the modern era.&lt;/p&gt;
&lt;p&gt;Notably, the model estimates the current proportion of resistant strains to be 14%  --  close to empirically-derived estimates of 13% to 16%, the researchers said.&lt;/p&gt;
&lt;p&gt;In the next five years, the model predicts, resistance to two classes of drugs  --  protease inhibitors and nucleoside reverse transcriptase inhibitors  --  will remain relatively low.&lt;/p&gt;
&lt;p&gt;But resistance to the third major class  --  the non-nucleoside reverse transcriptase inhibitors  --  will increase, the model suggests.&lt;/p&gt;
&lt;p&gt;The conventional wisdom, Blower said, has been that resistant strains are less fit than wild-type virus and thus less able to infect new patients.&lt;/p&gt;
&lt;p&gt;But currently, Blower said, about 60% of resistant strains circulating in San Francisco are sufficiently fit that they could be transmitted to more than one person.&lt;/p&gt;
&lt;p&gt;And about three-quarters of those are resistant to the non-nucleoside reverse transcriptase inhibitors, the researchers said.&lt;/p&gt;
&lt;p&gt;&quot;The strains that are resistant to the non-nukes are actually pretty fit,&quot; Blower said, &quot;almost as fit as wild-type strains.&quot;&lt;/p&gt;
&lt;p&gt;One implication, she said, is that therapy in the developing world  --  where the non-nucleoside reverse transcriptase inhibitors are mainstays  --  may lead to a new wave of resistance that could cripple efforts to slow the pandemic.&lt;/p&gt;
&lt;p&gt;Robert Schooley, MD, of the University of California San Diego, said drug resistance &quot;is the inevitable result of antimicrobial agents.&quot;&lt;/p&gt;
&lt;p&gt;Schooley said in an e-mail that there&apos;s no reason not to treat people who need care, but &quot;it is critical to use drugs when the benefits (for the individual or the population) outweigh the risks.&quot;&lt;/p&gt;
&lt;p&gt;Specifically, he said, it&apos;s important to monitor viral load to ensure that the virus is adequately suppressed and that resistance is not developing.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The researchers had support from the National Institute of Allergy and Infectious Diseases, the Natural Sciences and Engineering Research Council of Canada, MITACS, the John Simon Guggenheim Foundation, the National Academies Keck Foundation, and the Semel Institute for Neuroscience &amp;amp; Human Behavior. The researchers did not report any conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;&lt;p&gt;&lt;em&gt;This article was developed in collaboration with ABC News. &lt;/em&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; alt=&quot;&quot;&gt;&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_113"
                     title="HIV Switch Trial Succeeds and Fails (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/17922?impressionId=1265747274396"
                     
      Changing HIV drug regimens reduced metabolic side effects in two clinical trials, researchers said  --  but, unfortunately, the switch resulted in some loss of control over the virus.&lt;br&gt;
&lt;br&gt;The unexpected loss of efficacy when patients changed from lopinavir and ritonavir (Kaletra) to raltegravir (Isentress) led to the trials being halted after 24 weeks, Peter Sklar, MD, of Merck Research Laboratories in North Wales, Pa., and colleagues reported online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;Even so, the finding may not rule out the switch in some patients, the investigators said in the journal. An unplanned analysis showed that patients without a previous virological failure did equally well in both arms of the trial, they reported.&lt;br&gt;
&lt;br&gt;This means the results &quot;will probably generate some debate and controversy,&quot; J. Michael Kilby, MD, of the Medical University of South Carolina in Charleston, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Although the unplanned analysis can&apos;t prove anything, he noted, it seems likely that cross-resistance to raltegravir, a so-called integrase inhibitor, had built up in some patients during previous treatment failures, even though they had not taken the drug itself.&lt;/p&gt;
&lt;p&gt;The result &quot;is a reminder that whenever possible, to assure sustained dependable activity, even our most promising antiretroviral agents should be used in combination with two or more fully active drugs,&quot; Kilby said.&lt;/p&gt;
&lt;p&gt;Protease inhibitors  --  such as lopinavir and ritonavir  --  have been associated with metabolic abnormalities such as elevated triglycerides, although other HIV drugs can also cause those and other side effects.&lt;/p&gt;
&lt;p&gt;But adverse events associated with raltegravir appeared to be minimal, so the drug&apos;s manufacturer, Merck, began parallel randomized, double-blind, double-dummy trials to test whether switching from stable lopinavir-ritonavir therapy to raltegravir would improve matters.&lt;/p&gt;
&lt;p&gt;All patients in the study would also continue background therapy with two or more nucleoside or nucleotide reverse transcriptase inhibitors.&lt;/p&gt;
&lt;p&gt;Combined, the two studies had 702 patients, with 350 switched to raltegravir and 352 remaining on lopinavir-ritonavir.&lt;/p&gt;
&lt;p&gt;Over the first 12 weeks after the switch, percentage changes in lipid concentrations were significantly greater at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001 in the raltegravir groups than in the lopinavir-ritonavir groups.&lt;/p&gt;
&lt;p&gt;Specifically: &lt;ul&gt; &lt;li&gt;Total cholesterol declined 12.6% among the raltegravir patients, compared with a gain of 1% among those who did not switch.&lt;/li&gt; &lt;li&gt;Non-HDL cholesterol fell 15% versus a gain of 2.6%. &lt;/li&gt; &lt;li&gt;Triglycerides declined 42.2% versus a gain of 6.2%.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;However, at week 24, only 84.4% of the patients in the raltegravir group had a viral load of less than 50 copies of viral RNA per milliliter of blood. In contrast, 90.6% of the lopinavir-ritonavir group had a viral load below that level.&lt;/p&gt;
&lt;p&gt;The treatment difference of minus 6.2 percentage points meant that raltegravir didn&apos;t meet a preset test for noninferiority.&lt;/p&gt;
&lt;p&gt;On the other hand, when the analysis was restricted to patients who had not previously experienced a treatment failure, the researchers found, success rates were not significantly different between the groups  --  89% for raltegravir and 90% for lopinavir-ritonavir.&lt;/p&gt;
&lt;p&gt;The finding &quot;underscores the complex considerations involved in providing the best possible treatment regimens for individual patients,&quot; Sklar and colleagues said in the journal.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The studies were sponsored by Merck. Sklar is an employee of the company and several other authors reported financial links with Merck or other pharmaceutical companies.&lt;/p&gt;&lt;p&gt;Kilby reported he had previously received research support from Merck.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>
