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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_217"
                     title="Herpes Therapy Doesn&apos;t Bar HIV Transmission (CME/CE)"
                     score="-0.003"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/18071?impressionId=1265797924138"
                     
      &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="20090101_19_3515"
                     title="AASLD: New Drug Boosts HCV Clearance (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/AASLD/tb/16763?impressionId=1265797924138"
                     
      BOSTON  --  Most hepatitis C patients who are initially unresponsive to standard therapy were able to achieve sustained virologic responses when the investigational drug boceprevir was added, a researcher reported here.&lt;br&gt;
&lt;br&gt;Sustained responses were seen in 55% of patients receiving 44 weeks of boceprevir after showing no virologic response to four weeks of pegylated interferon-alfa-2b (PEGIntron) and ribavirin (Rebetol) in a Phase II trial, said Paul Kwo, MD, of Indiana University in Indianapolis.&lt;br&gt;
&lt;br&gt;Kwo, speaking here at the American Association for the Study of Liver Disease meeting, was reporting on two secondary analyses of data from the SPRINT-1 trial of boceprevir, an inhibitor of the hepatitis C virus (HCV) NS3 protease enzyme.&lt;br&gt;
&lt;br&gt;He had presented the main findings of the 520-patient study earlier this year at the European Association for the Study of the Liver meeting in Copenhagen. (See &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/13894&quot; mce_href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/13894&quot; target=&quot;_blank&quot;&gt;Sustained Response Seen with New Hepatitis C Drug&lt;/a&gt;)&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Boceprevir is one of two HCV protease inhibitors in late-stage development, the other being telaprevir. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/DDW/14515&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/DDW/14515&quot; target=&quot;_blank&quot;&gt;DDW: Telaprevir Improves HCV Clearance in Resistant Patients&lt;/a&gt;) Phase III trials of both drugs are now under way.&lt;/p&gt;
&lt;p&gt;In the SPRINT-1 trial, treatment-naive patients were randomized to five treatment arms, including one in which patients only received pegylated interferon and ribavirin, two involving immediate treatment with all three agents, and two in which boceprevir started after an initial, four-week lead-in with interferon and ribavirin.&lt;/p&gt;
&lt;p&gt;All patients had HCV genotype 1a or 1b, mostly the former.&lt;/p&gt;
&lt;p&gt;The secondary analyses reported here focused only this last treatment strategy, with patients receiving either 24 or 44 weeks of triple therapy following the four-week, two-drug lead-in.&lt;/p&gt;
&lt;p&gt;Boceprevir was dosed at 800 mg three times a day.&lt;/p&gt;
&lt;p&gt;In patients with no response to the lead-in  --  defined as a reduction in HCV RNA loads of less than ten-fold  --  25% of those receiving boceprevir for 24 weeks still showed viral clearance after an additional 24 weeks of follow-up.&lt;/p&gt;
&lt;p&gt;With 55% of initial null responders receiving the drug for 44 weeks showing long-lasting viral clearance, the longer therapy appeared to be more effective, Kwo said.&lt;/p&gt;
&lt;p&gt;He also noted that boceprevir for both durations boosted response rates well above what would normally be expected from standard therapy in patients without strong responses in the first four weeks.&lt;/p&gt;
&lt;p&gt;He cited results from an earlier large trial in which less than 5% of early nonresponders to standard therapy eventually developed sustained responses.&lt;/p&gt;
&lt;p&gt;Among patients showing strong responses in the first four weeks of interferon and ribavirin, sustained responses were seen in most.&lt;/p&gt;
&lt;p&gt;More than 80% of those with initial reductions of three to four orders of magnitude in viral RNA levels had sustained responses, as did nearly 100% of those with reductions of at least four orders of magnitude or whose viral RNA became undetectable in the first four weeks.&lt;/p&gt;
&lt;p&gt;Duration of boceprevir treatment appeared to make no difference in sustained virologic response rates in these patients.&lt;/p&gt;
&lt;p&gt;But Kwo cautioned that the findings in these analyses involved relatively small numbers of patients. Only about 50 patients were considered null responders to the lead-in treatment, and similar numbers had relatively strong initial responses.&lt;/p&gt;
&lt;p&gt;Overall, adding boceprevir after the four-week lead-in led to sustained responses in 56% of patients receiving boceprevir for 24 weeks, and in 75% of those taking the drug for 44 weeks, Kwo said. Both response rates were significantly (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) higher than the 38% rate seen in patients taking only pegylated interferon and ribavirin for 48 weeks.&lt;/p&gt;
&lt;p&gt;In a separate analysis, Kwo reported that virologic responses measured later in treatment could identify patients for whom longer or shorter boceprevir treatment would be most appropriate.&lt;/p&gt;
&lt;p&gt;For example, only the 18% of patients whose viral RNA became undetectable after four to 12 weeks of boceprevir treatment (after the four-week lead-in with standard therapy) appeared to need the full 44 weeks of boceprevir to hold the response, Kwo said. The remaining 82% all achieved viral clearance within four weeks of starting boceprevir.&lt;/p&gt;
&lt;p&gt;He said he hoped the Phase III trial would confirm that most patients could get by with the shorter regimen.&lt;/p&gt;
&lt;p&gt;He added that the overall data suggested that HCV protease inhibitors may act primarily to restore sensitivity to interferon, though he emphasized that this theory would have to be confirmed in future studies.&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 was funded by Schering-Plough.&lt;/p&gt;&lt;p&gt;Kwo reported relationships with Schering-Plough, Vertex, Novartis, Gilead, Abbott, Roche, Merck, GlaxoSmithKline, Celgene, Idenex, and Bristol-Myers Squibb. Several co-authors were employees of Schering-Plough.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3578"
                     title="AASLD: Treating Before Transplant Cuts HCV Recurrence (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/AASLD/tb/16848?impressionId=1265797924138"
                     
      BOSTON  --  In patients with advanced liver disease related to hepatitis C, a course of pegylated interferon and ribavirin (Rebetol) before liver transplant may help them avoid recurrence of infection, a researcher said here.&lt;br&gt;
&lt;br&gt;Nearly 30% of patients receiving the drugs showed no signs of the hepatitis C virus (HCV) three months after receiving a new liver, reported Gregory T. Everson, MD, of the University of Colorado in Denver.&lt;br&gt;
&lt;br&gt;He presented results of a prospective, semirandomized component of a larger study called A2ALL at the American Association for the Study of Liver Diseases meeting.&lt;br&gt;
&lt;br&gt;&quot;This experience supports the concept that pretransplant therapy can prevent allograft reinfection,&quot; he said.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Not surprisingly, the best results were achieved in patients whose HCV viral loads were reduced to undetectable levels at the time of transplant, Everson reported. Among 14 patients in whom this was achieved, eight remained virus free at the post-transplant evaluation.&lt;/p&gt;
&lt;p&gt;Duration of the pretreatment regimen was also a significant predictor of post-transplant response, Everson reported.&lt;/p&gt;
&lt;p&gt;Some 44% of patients who received the interferon-ribavirin treatment for more than 15 weeks before transplant had a postprocedure response, compared with 18% of those treated for 10 to 15 weeks and 15% of those getting the drugs for less than 10 weeks (&lt;em&gt;P&lt;/em&gt;=0.04).&lt;/p&gt;
&lt;p&gt;Other factors  --  such as baseline HCV viremia, viral genotype, type of donor (live versus dead), and toxicity-related dose limitations  --  were not significantly associated with post-transplant response, although the study may not have been powered adequately to detect such associations.&lt;/p&gt;
&lt;p&gt;Of the 79 patients enrolled in the trial, 47 with HCV genotypes 1, 4, 5, or 6 were randomized in a 2:1 ratio to receive the pretransplant drug regimen or no treatment. All of the 32 other patients with HCV genotypes 2 or 3 received the treatment.&lt;/p&gt;
&lt;p&gt;The treatment consisted of starting doses of 0.75 mcg/kg/week of pegylated interferon-alfa-2b (PEGIntron) and 600 mg/day of ribavirin, which were both escalated as tolerated over several weeks to standard target levels.&lt;/p&gt;
&lt;p&gt;Median treatment duration was 11.4 weeks for the 44 dead-donor candidates and 14.6 weeks for the 35 able to receive live-donor organs.&lt;/p&gt;
&lt;p&gt;Transplant was actually performed in 41 patients, 25 of whom were dead-donor candidates.&lt;/p&gt;
&lt;p&gt;Everson characterized the effectiveness of the pretransplant drug regimen as &quot;limited.&quot;&lt;/p&gt;
&lt;p&gt;He said it should be considered only for selected patients, particularly those with relatively less severe disease.&lt;/p&gt;
&lt;p&gt;In the trial, those were the patients who were live-donor candidates along with the dead-donor candidates who received a so-called MELD upgrade because of hepatocellular carcinoma.&lt;/p&gt;
&lt;p&gt;&quot;If you take all the patients with HCV going to liver transplant, many of them are too sick to treat with [pegylated interferon] and ribavirin,&quot; he said.&lt;/p&gt;
&lt;p&gt;Data from the study indicated that the treatment was significantly toxic. Three-quarters of the treated patients suffered serious adverse events, compared with half of untreated patients (&lt;em&gt;P&lt;/em&gt;=0.04). These were seen both before and after transplant.&lt;/p&gt;
&lt;p&gt;However, mortality rates were the same in treated and untreated patients, at about 15%.&lt;/p&gt;
&lt;p&gt;Everson said it might be possible in the future to try pretreatment in sicker patients when direct antiviral drugs for HCV become available.&lt;/p&gt;
&lt;p&gt;In the meantime, he said, patients who can tolerate the treatment need to stay on it for at least 12 weeks.&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 was funded by the National Institutes of Health.&lt;/p&gt;&lt;p&gt;Everson reported relationships with Schering-Plough and Ortho Biotech. Other co-authors reported relationships with Roche, Salix, Gilead, Vertex, Pfizer, GlaxoSmithKline, Amgen, Bayer, Novartis, and Human Genome Sciences, among others.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_482"
                     title="AASLD: Weight-Based Dosing of Rebetol Improves Outlook for HCV"
                     score="-0.006"
                     href="