Interferon-free Regimen for Hepatitis C Advances

Medscape Medical News > Conference News

Neil Canavan

Jul 11, 2013

KUALA LUMPUR, Malaysia — A new interferon-free drug regimen for the treatment of hepatitis C is safe and effective in treatment-naïve patients and in those who previously had a poor response to treatment, according to the phase 2b AVIATOR trial.

The direct-acting antiviral combination, manufactured by AbbVie Pharmaceuticals, consists of the protease inhibitor ABT-450, the non-nucleoside NS5B polymerase inhibitor ABT-333, and the novel NS5A inhibitor ABT-267. When used in combination with ribavirin, it reportedly produces sustained virologic response rates of up to 99% in patients with hepatitis C.

Barry Bernstein, MD, vice president of infectious disease at AbbVie, and his team evaluated the safety and efficacy of this interferon-free regimen in combination with ribavirin to determine whether toxic events would lead to dose reductions in ribavirin and whether that would have any effect on treatment outcome.

Ribavirin is a key component of effective hepatitis C treatment, but often it cannot be used at optimum therapeutic levels when combined with interferon — the current standard of care.

Dr. Bernstein presented the results here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

“These results, if they hold up, will be very significant for people coinfected with HIV and hepatitis C.”

In the AVIATOR trial, first presented last year at the annual meeting of the American Association for the Study of the Liver Diseases, patients were treated with the interferon-free combination with or without ribavirin for 12 or 24 weeks.

In the study cohort, 159 patients were treatment-naïve and 88 were previous nonresponders to ribavirin. Median age was 50 years, and was 86% of the cohort was white. All patients had chronic infection with hepatitis C genotype 1 and plasma HCV RNA levels above 50,000 IU/mL.

The primary end points were safety and sustained virologic response at 24 weeks.

Four patients (1.6%) discontinued treatment because of adverse events, 1 patient experienced a serious adverse event (arthralgia), and 16 patients (6.5%) had hemoglobin levels below 10 g/dL.

In 24 of the 247 (10%) patients, the dose of ribavirin was reduced because of adverse events. Of these, 20 were treatment-naïve and 4 were previous nonresponders.

The incidence of ribavirin dose reductions was similar in the 12- and 24-week treatment groups.

The most common adverse events were anemia, with 10 events reported, and fatigue, with 3 events reported. Other events, with 2 reports each, were diarrhea, dizziness, and pruritus.

There were more adverse events in treatment-naïve patients than in nonresponders.

All 24 patients whose dose of ribavirin was reduced achieved a sustained virologic response at 24 weeks. For those without a dose reduction, 92.1% of the treatment-naïve patients and 94.0% of the nonresponders achieved a sustained virologic response at 24 weeks

"Significantly, ribavirin dose reduction occurred less frequently than in previous studies of peg-interferon-containing regimens," said Dr. Bernstein. As important, he noted, is the fact that when dose reductions did occur, response rates were not negatively affected.

Toward Interferon-free Treatment

Preliminary trials to determine drug–drug interactions with HIV medications are near completion, and a trial of this drug combination in patients coinfected with HIV and hepatitis C will start soon, Dr. Bernstein said.

These results, if they hold up, will be very significant for people coinfected with HIV and hepatitis C, said Tom Campbell, MD, a principal investigator of the Colorado AIDS Clinical Trial Unit. "The exciting thing is that they don't require the use of interferon, which is very poorly tolerated, particularly in people with coinfection."

The need for interferon-free regimens is clear. "We have patients who are waiting for new drugs before they are willing to be treated, particularly those who have less advanced hepatitis C infection who don't need immediate treatment," Dr. Campbell explained. He acknowledged that "it will be a few years before these drugs are approved for HIV and hepatitis C coinfection, so it is a bit of a gamble to wait."

However, he understands the reluctance of these patients to be treated now. "It's a decision that the patient should make in consultation with their care provider."

Dr. Bernstein is an employee of AbbVie Pharmaceuticals. Dr. Campbell has disclosed no relevant financial relationships.

7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract TUAB0103. Presented July 2, 2013.

Source

Hepatitis C Reinfection Rising Among HIV Patients

Medscape Medical News > Conference News

Neil Canavan

Jul 11, 2013

KUALA LUMPUR, Malaysia — Nearly 25% of HIV patients infected with and subsequently cured of the hepatitis C virus went on to acquire a second or even third infection within 24 months at one hospital in the United Kingdom.

"Liver disease is one of the leading non-AIDS causes of death in HIV-infected individuals," said lead investigator Thomas Martin, from the Chelsea and Westminster Hospital in London, United Kingdom. In fact, hepatitis C accounted for "roughly two thirds of those cases."

These results suggest that much better educational initiatives related to coinfection with HIV and hepatitis C are needed, he noted.

It has previously been shown that coinfection with HIV reduces the spontaneous clearance of hepatitis C infection, reduces the rate of successful treatment, and can lead to a 3-fold increase in the rate of progression to cirrhosis.

However, the extent to which HIV patients are reinfected with hepatitis C has not been established.

To look at this issue, Dr. Martin and his team analyzed reinfection rates in 191 HIV patients with a primary hepatitis C infection treated at the Chelsea and Westminster Hospital.

Dr. Martin presented the results here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

“Liver disease is one of the leading non-AIDS causes of death in HIV-infected individuals.”

The researchers defined reinfection as any newly positive hepatitis C virus RNA polymerase chain reaction result 24 weeks or more after the end of hepatitis C treatment, spontaneous clearance of the virus, or the emergence of a different hepatitis C genotype in a 24-month period.

In the study cohort, the rate of hepatitis C reinfection was 7.8 per 100 patient-years (95% confidence interval, 5.8 - 10.5). "That's approximately 5 to 10 times the baseline primary infection incidence of hepatitis C in this population," Dr. Martin explained.

Of the 32 reinfected patients, the hepatitis C infection was cleared with treatment or spontaneous remission in 17 patients. Of those, 8 went on to acquire a third hepatitis C infection, resulting in an infection rate of 23.2 per 100 patient-years.

Overall, the second and third reinfections cleared spontaneously in 20% of patients, and a complete viral clearance was achieved with standard-of-care treatment in 80%.

"We saw no evidence of protective immunity from the initial hepatitis C infection," said Dr. Martin. "In fact, these individuals remain at high risk for reinfection."

Coinfection Education Needed

"We're becoming increasingly aware that gay men have this elevated risk of sexual acquisition of hepatitis C," said Charles Hicks, MD, professor of medicine at Duke University in Durham, North Carolina.

However, the high frequency of reinfection over a fairly short period after the initial hepatitis C diagnosis is "striking," Dr. Hicks told Medscape Medical News. "That was alarming to me. It means we need to do a better job of counseling gay men who have hepatitis C that just because their first infection has been managed successfully, it doesn't mean they are no longer at risk." Prevention here is key.

It also has implications for future monitoring of patients. Typically, an active hepatitis C infection is detected with an antibody test, he explained. "But in cases of previous viral clearance, you're going to have to use an RNA viral load test to find cases of reinfection."

Dr. Marin and Dr. Hicks have disclosed no relevant financial relationships.

7th International AIDS Society (IAS) Conference on HIV Pathogenesis: Abstract TUAB0101. Presented July 2, 2013.

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Tenofovir Lowers HIV Risk in Drug Abusers by Half

Medscape Medical News > Conference News

Neil Canavan

Jul 11, 2013

KUALA LUMPUR, Malaysia — A large study of intravenous drug users has found a surprisingly high rate of adherence to pre-exposure prophylaxis with tenofovir, resulting in a marked reduction in new HIV infections.

"The study tells us that pre-exposure prophylaxis can work for all populations at risk for HIV, including people who inject drugs," said study investigator Michael Martin, MD, from the Centers for Disease Control and Prevention in Atlanta, Georgia.

Dr. Martin presented findings here at the 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.

The double-blind placebo-controlled Bangkok Tenofovir Study involved 2413 intravenous drug users. The cohort was 80% male, and the average age was 31 years.

Investigators randomized participants to receive daily oral tenofovir 300 mg or placebo. "We provided monthly HIV testing, participant-centered risk-reduction and adherence counseling, blood safety testing every 3 months, condoms, and methadone treatment," said Dr. Martin.

Participants were asked to record their medication use in an adherence diary or were directly observed taking the study drug. At monthly visits, the staff and the participant reviewed the adherence diary and did a pill count.

Results showed that participants took the drug 84% of the time, which translated into a substantial reduction in the rate of HIV infection. "We had 17 new infections in the tenofovir group and 33 in the placebo group," Dr. Martin reported. "This translates into a 49% reduction in risk (P = .01)."

Adherence did not differ by treatment group (P = .16). However, older participants were more adherent than younger participants (P < .001), and women were more adherent than men (P = .04).

"Needle sharing and sexual risk were similar in the 2 study arms," Dr. Martin explained. However, participants reported that these behaviors declined substantially during the trial. "This was true for both treatment groups."

Despite the positive data that continue to emerge for pre-exposure prophylaxis, real-world use remains limited. Antiretroviral medications for pre-exposure prophylaxis are "not flying off the shelf," Robert Grant, MD, lead investigator of the landmark Pre-Exposure Prophylaxis Initiative (iPrEx) trial, told reporters attending a news conference.

Perceptions From the iPrEx Trial

"We're finding that demand for such services and people interested in providing pre-exposure prophylaxis to their clients remain relatively low. We think that part of this is that it takes time for people to get their heads around new ideas, but part of it is that we really do need to learn more about how best to provide pre-exposure prophylaxis and how best to promote it's effective use."

At the IAS meeting, Dr. Grant reported recent findings from an open-label extension of the iPrEx trial, in which 65% of the original 2340 patients participated. Of the 1451 participants who were not infected with HIV at the time of enrollment in the extension study, 1038 chose to receive pre-exposure prophylaxis.

"We were impressed that 72% of those offered pre-exposure prophylaxis chose to participate, and of those who did, 72% had detectable drug levels," he reported.

That said, it's obvious that pre-exposure prophylaxis is not for everyone, Dr. Grant noted. "It's for people who perceive themselves to be at risk. If roughly half of iPrEx participants are able to appropriately use pre-exposure prophylaxis, that's a substantial number."

Dr. Martin has disclosed no relevant financial relationships. Dr. Grant reports serving as an advisor and consultant for Siemens AG.

The 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstracts WELBC05 and WELBC02. Presented July 3, 2013.

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Black Market for HIV Antiretroviral Drugs Booming

Medscape Medical News > Conference News

Neil Canavan

Jul 10, 2013

KUALA LUMPUR, Malaysia — A disturbing number of men with legal access to antiretroviral medications are selling their prescriptions on the black market, according to new research.

These diverted medications mean an increase in the ongoing risk for HIV transmission and treatment failure because of resistance to therapy in those who become infected.

"We started receiving law enforcement reports about drug diversions around 5 years ago from major cities in the United States," said Steven Kurtz, PhD, from the Center for Applied Research on Substance Use and Health Disparities in Coral Gables, Florida. "It quickly became clear that street markets had developed for antiretroviral medications."

A previous study looking at this problem in impoverished men found a diversion rate as high as 20%. What Dr. Kurtz and his team set out to establish in their investigation was the extent of diversion practices in men who have sex with men.

Dr. Kurtz presented the research here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

The teams used the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) drug database to establish the prevalence of diversion. The system collects information from 300 law enforcement jurisdictions in the United States on sources of diversion such as undercover street purchases, arrests for distribution, and hospital and pharmacy theft.

It quickly became clear that street markets had developed for antiretroviral medications.

The RADARS data showed that 1518 cases of diversion had been investigated in 7 geographically diverse jurisdictions over 39 calendar quarters.

Dr. Kurtz and his team used this information to develop a survey about medical care, treatment, and adherence and diversion. It was completed by 515 men.

Of the 46.4% of respondents who were infected with HIV, 91.6% were receiving medical care. Nearly 80% of these men were prescribed much-needed antiretrovirals, yet 27.5% reported selling or trading their medications at some point, and 19.0% reported doing so in the previous year.

The respondents reported diverting their medications to share or trade with friends, to acquire money or illicit drugs, or to get rid of unused medications. Not surprisingly, antiretroviral diverters were more likely to be dependent on substances than nondiverters (74.5% vs 58.7%; P = .046), and more diverters reported recently trading sex for money or drugs (60.8% vs 32.6%).

Who is buying these drugs?

The demand for antiretrovirals increased with their recent approval for pre-exposure prophylaxis.

Party Packs Called MTV

"We've known from the literature and anecdotally that tenofovir, specifically, has been used for pre-exposure prophylaxis since at least 2009," Dr. Kurtz explained. It was even being distributed in clubs in Miami and other cities as a party pack called MTV, which consists of methamphetamine, emtricitabine plus tenofovir (Truvada), and sildenafil (Viagra). "That was a strong signal about what was going on."

"Frankly, we don't know who the purchasers are. Pill brokers are likely a big part of it, going in the back door of pharmacies, and recirculation. We need studies now to look at the demand side," he said.

"There's been a big black market in South Florida for many years," said Michael Weinstein, president of the AIDS Healthcare Foundation. "First off, Miami is the capital of Latin America. If the drugs are not available back home, you go to Miami. However, that's changed over time as treatment has become more common in poorer countries, so the incentive is now somewhat less."

Another market is individuals who are undocumented, explained Weinstein. "Usually, if you need to reduce the expense of your medications, you go to a government-sponsored clinic, but that requires providing some kind of information about yourself. Even though places like the Ryan White Program do cover undocumented patients, there are many who fear engagement with a government-run or any other type of formal facility."

Weinstein said that Gilead, the maker of Truvada, is somewhat complicit in the creation of the black market by aggressively promoting a product that, he believes, should not have been approved as a preventive measure in the first place.

"The whole premise of pre-exposure prophylaxis is dangerous and unwarranted based on study results. In the real world, pre-exposure prophylaxis relies on adherence, which in my opinion cannot be accomplished. People who already have the virus are often noncompliant. What you're going to wind up with is more infections and more resistance."

Dr. Kurtz and Mr. Weinstein have disclosed no relevant financial relationships.

The 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract MOPE133. Presented July 1, 2013.

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Liver stiffness more predictive of decompensation than biopsy results in HIV/HCV coinfection

Provided by Healio

July 9, 2013

Liver stiffness measurement is similarly predictive of overall mortality and more predictive of decompensation than liver biopsy results among patients with HIV/HCV coinfection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated 297 patients coinfected with HCV and HIV who underwent liver biopsy (LB) and liver stiffness measurement (LSM) within 12 months of one another. The midway point between the procedures was considered the baseline date for analysis. Ninety-three percent of participants were receiving therapy with antiretrovirals at baseline, with undetectable plasma HIV RNA levels in 79% of cases and a median CD4 cell count of 514 cells/mcL.

Among evaluable participants after 26 cases were lost to follow-up, overall mortality across the cohort was 1.56 deaths per 100 person-years. Increased risk for death was associated with elevated LSM values (adjusted HR=1.28; 95% CI, 1.12-1.46 per 5 kPa increase) and fibrosis stage at baseline as indicated by LB (aHR=1.56; 95% CI, 1.02-2.4). Liver decompensation occurred at a rate of 1.59 cases per 100 person-years, with LSM (aHR=1.37; 95% CI, 1.21-1.54) and fibrosis stage at baseline (aHR=1.67; 95% CI, 1.15-2.43) as predictive factors.

Integrated discrimination improvement (IDI) analysis indicated that models incorporating LMS values performed 3.9% better in predicting mortality than models incorporating LB, but was not statistically significant (P=.072). For the prediction of liver decompensation, LMS-based models performed 8.4% better than LB-based models (P=.045).

“LSM-based prediction achieves a similar yield [to] LB-based models to predict overall mortality in HIV/HCV coinfected patients, and the former could better predict liver decompensations,” the researchers concluded. “LSM may replace LB as [a] prognostic tool in this setting.”

For more information:

Macías J. TUAB0104: Prediction of Survival and Decompensations of Cirrhosis Among HIV/HCV Coinfected Patients: A Comparison of Liver Stiffness Versus Liver Biopsy. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Poorer antiretroviral response among HIV patients with HBV, HCV coinfection

Provided by Healio

July 9, 2013

Patients with HIV coinfected with hepatitis B or hepatitis C virus experienced poorer outcomes from antiretroviral therapy compared with monoinfected patients in a study presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated data collected from the TREAT Asia HIV Observational Database on 7,455 patients with HIV treated at 22 Asian hospitals. All participants received antiretroviral therapy (ART), with a target HIV viral load (VL) of fewer than 1,000 copies/mL. Among patients with evaluable test results, 10.45% were coinfected with HBV and 15.2% with HCV.

After 180 days of therapy, CD4 counts were significantly lower among patients coinfected with either HBV (adjusted difference=–15.5 cells/mcL; P=.011) or HCV (aDiff=–37.8 cells/mcL; P<.001) compared with monoinfected patients after initiating ART. CD4 increases were smaller among those with HIV subtype CRF01AE compared with subtype B (–35.5 cells/mcL; P=.026).

The target VL was achieved in a median of 1.28 years within the cohort. Patients coinfected with HBV or HCV experienced a longer time to VL than monoinfected participants, but this difference was not statistically significant.

Coinfected patients had poorer survival than monoinfected patients. Multivariate analysis indicated a significant association between mortality and HCV coinfection (adjusted HR=1.81; 95% CI, 1.2-2.71). No association was observed between HIV VL and coinfection with either HBV or HCV.

“In this Asia regional HIV cohort, patients with HBV or HCV coinfection had significantly lower CD4 counts [and] smaller CD4 increases after 180 days of ART,” the researchers concluded. “We need to test, identify and initiate [highly active] ART early in HBV and HCV coinfected [patients] to have a better treatment effect.”

For more information:

Chen YMA. TULBPE13: HBV and HCV Coinfection: Long-term Immunological, Virological and Survival Outcomes Following cART. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Poor treatment outcomes common among children with HIV/HCV coinfection

Provided by Healio

July 8, 2013

European children with HIV/HCV coinfection often have poor outcomes from HCV therapy, according to results presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

In a retrospective case note review, researchers identified 10 patients collected from four of 10 evaluated cohorts containing one or more patients coinfected with hepatitis C and HIV aged younger than 25 years. All patients had perinatal or early childhood HIV acquisition and had received HCV therapy with either pegylated interferon alfa-2a or alfa-2b (n=5 each) with ribavirin for a median duration of 48 weeks.

“Little is known about anti-HCV therapy and its outcomes in HIV/HCV coinfected children,” the researchers wrote. “Our aim was to document use and effectiveness of HCV treatment in HIV/HCV coinfected children and young people in Europe.”

The cohort included six females and four males, with eight cases of HCV genotype 1, one genotype 4 and one with an unknown genotype. The patients (median age at treatment initiation, 17.1 years) had a median HCV infection duration of 13.4 years. Among seven cases with evaluable fibrosis, stage F2 was observed in two cases, F3 in three and F4 in two cases.

One participant experienced early response, defined as undetectable HCV RNA at 12 weeks, and later achieved sustained virological response. No other participants experienced early or sustained response to therapy. No patients discontinued treatment due to adverse events, though investigators noted two cases of decreased neutrophil counts during treatment. One patient, who required retreatment 2 years after the treatment included in this study, died after liver transplantation.

“There is a very limited experience of treating HCV in HIV/HCV coinfected children,” the researchers concluded. “Our results show poor treatment outcomes in these cases, most of whom had advanced fibrosis and [genotype 1].”

For more information:

Turkova A. WEPE484: HCV Treatment in Children and Young Adults with HIV/HCV Coinfection in Europe. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Interferon-based therapy similarly effective with normal, elevated ALT in HCV/HIV coinfected patients

Provided by Healio

July 8, 2013

Treatment with pegylated interferon alfa-2a and ribavirin yielded similar response rates in patients with HIV and HCV coinfection with elevated and persistently normal ALT in a study presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

In the prospective, multicenter CONTRA study, researchers administered 180 mcg peginterferon-alfa-2a weekly and 1,000 mg to 1,200 mg ribavirin daily for 48 weeks to 80 patients coinfected with HIV and HCV. The cohort included 42 patients with normal ALT levels as measured five or more times within the prior 2 years (case group) and 38 patients with elevated ALT (controls). The two groups were similar with regard to age, sex, BMI, HCV genotype prevalence and HCV viral load.

Within the ITT population, sustained virologic response occurred at similar rates between the case (38%) and control groups (42%) (P=.7). Complete response also was observed in a similar number of participants between groups at week 4 (32% of cases vs. 33% of controls) and week 12 (49% vs. 60%) (P=.56).

Seventy-one percent of cases and 84% of controls experienced adverse events. Treatment discontinuation was required in 10% and 5% of patients, respectively, and one incident of opportunistic infection was observed in the control group. Treatment modification was required in 41% of cases and 45% of controls.

“The treatment with peginterferon-alfa-2a and ribavirin in coinfected patients with persistently normal ALT levels has a similar efficacy to the one observed in patients with elevated ALT serum,” the researchers concluded. “Regarding toxicity, no significant differences were detected between both groups. The same treatment criteria should be used in both types of coinfected patients.”

For more information:

von Wichmann MA. WEPE486: PegIFN-alfa-2a and Ribavirin in HIV-HCV Coinfected Patients with Persistently Normal Aminotransferase Levels: Final Results of the CONTRA Study. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

Source

Early Therapy May Lead to HIV Remission

Published: Jul 7, 2013

By Michael Smith, North American Correspondent, MedPage Today

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• These preliminary results from a randomized trial demonstrated that early HIV therapy in patients with symptoms of primary infection or CD4 counts < 500/mm³ led to marked reduction in viral DNA.
• Be aware that the primary purpose of the trial -- to evaluate the feasibility of stopping therapy in select patients -- has yet to be reported.

KUALA LUMPUR -- Preliminary data from a French randomized trial suggest that early HIV treatment might be a step toward so-called post-treatment control, a researcher said here.

Post-treatment control is what investigators are calling the ability to stop HIV therapy -- after some time on treatment -- without having the virus resume replication within the body.

Some 14 patients -- known as the Visconti cohort and all treated within weeks of their infection -- have been shown to have such control, some for several years, according to Antoine Cheret, MD, of Sorbonne-Paris-Cite University in Paris.

At the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention here, Cheret presented early data from the first randomized trial aimed at duplicating the Visconti cohort.

The Optiprim study has enrolled 90 patients with early HIV infection and randomly assigned them to 24 months of a standard triple-drug regimen -- boosted darunavir (Prezista) plus tenofovir/emtricitabine (Truvada) -- or the same regimen plus raltegravir (Isentress) and maraviroc (Selzentry).

The primary endpoint of the study is what happens to the levels of HIV DNA -- regarded as the indicator of the reservoir if HIV needed to resume replication -- after the treatment period.

But at that time, Cheret reported, investigators plan to stop treatment for 6 months to see if either regimen leads to post-treatment control.

The "only problem with the presentation is they didn't have the results," commented Robert Murphy, MD, of Northwestern University Feinberg School of Medicine in Chicago.

Nonetheless, Murphy, who's involved in studies aimed at eradicating HIV reservoirs as a potential step to remission, said the data Cheret presented -- overall information about control of HIV and decline in HIV DNA -- is important.

"This will help in designing future trials," he said, even though it's preliminary.

At baseline, Cheret reported, the 90 patients were within a few weeks of infection, had a median plasma viral load of 5.4 log₁₀ copies of HIV RNAS per milliliter, and a median of 472 CD4-positive T cells per microliter of blood.

They also had a median of 3.65 log₁₀ copies of HIV DNA per million peripheral blood mononuclear cells (PBMCs).

As expected, viral loads declined during treatment with 92% of patients having undetectable levels after a year and CD4 cell counts rose by a median of 235 cells.

And HIV DNA fell by a median of 1.43 log₁₀ copies per million PBMCs, while one in four patients had a drop of at least 2.0 log₁₀ copies, Cheret reported.

While it would have been nice to see the data broken down by treatment group, "these are very important numbers," Murphy commented.

The study had support from Merck, Janssen, ViiV Healthcare, and Gilead.

Cheret made no disclosures.

Murphy reported financial links with Gilead.

Primary source: International AIDS Society
Source reference:
Cheret A, et al "Impact of 12 months HAART on cell-associated HIV-DNA in acute primary HIV-1 infection in the OPTIPRIM-ANRS 147 trial" IAS 2013; Abstract WEAB0101.

Source

Stem-cell transplants may purge HIV

Daniel Kuritzkes, a researcher working with two 'Boston patients' who may have been cured of HIV, speaks at an AIDS conference in Kuala Lumpur, Malaysia.

International AIDS Society/Steve Forrest/Workers' Photos

Nature | News

But treatment is too risky for most people infected by the virus.

Erika Check Hayden

03 July

Two men with HIV may have been cured after they received stem-cell transplants to treat the blood cancer lymphoma, their doctors announced today at the International AIDS Society Conference in Kuala Lumpur.

One of the men received stem-cell transplants to replace his blood-cell-producing bone marrow about three years ago, and the other five years ago. Their regimens were similar to one used on Timothy Ray Brown, the 'Berlin patient' who has been living HIV-free for six years and is the only adult to have been declared cured of HIV. Last July, doctors announced that the two men — the ‘Boston patients’ — appeared to be living without detectable levels of HIV in their blood, but they were still taking antiretroviral medications at that time.

Timothy Henrich, an HIV specialist at Brigham and Women’s Hospital in Boston, Massachusetts, who helped to treat the men, says that they have now stopped their antiretroviral treatments with no ill effects. One has been off medication for 15 weeks and the other for seven. Neither has any trace of HIV DNA or RNA in his blood, Henrich says.

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If the men stay healthy, they would be the third and fourth patients ever to be cured of HIV, after Brown and a baby in Mississippi who received antiretroviral therapy soon after birth.

But Henrich and Daniel Kuritzkes, a colleague at Brigham who also worked with the men, caution that it is still too early know whether or not the Boston patients have been cured. For that, doctors will need to follow the men closely for at least a year, because the virus may be hiding out in 'reservoirs' — parts of the men’s bodies, such as their brain or gut, that can harbour the virus for decades.

“We’re being very careful not to say that these patients are cured,” Kuritzkes says. “But the findings to date are very encouraging.”

HIV researcher Steven Deeks of the University of California, San Francisco, says that doctors might need to wait at least two years before declaring that a cure has been achieved. “Any evidence that we might be able to cure HIV infection remains a major advance,” Deeks says. But, he adds, “there have been cases of patients who took many weeks off therapy before the virus took off”.

Exciting news

Still, researchers and doctors are excited about the news, especially because the Boston patients’ treatment differed from the Berlin patient’s regimen in one key way. Brown was given stem cells that were predisposed to resist HIV infection, because the donor happened to have a mutated version of a key protein — CCR5 — that is needed for HIV to infect cells. So Brown’s transplant was akin to gene therapy with HIV-resistant cells.

But the Boston patients received stem cells without the protective mutation. The transplanted cells must therefore have been protected from infection by the antiretroviral drugs taken during cancer treatment. Their doctors think that an immune response called graft-versus-host disease — a post-transplant reaction in which donated cells kill off a patient’s own cells — may have then wiped out the patients’ HIV reservoirs, potentially curing the men.

Transplant specialist Christine Durand of Johns Hopkins University School of Medicine in Baltimore, Maryland, says that the case of the Boston patients may show that current antiretroviral drugs are powerful enough, on their own, to protect the transplanted cells. “If cure has been achieved in the Boston patients, then it was the antiretroviral therapy, not gene therapy, that protected the donor cells,” she says.

The finding is very important for people with HIV who also need blood-cell transplants, but the treatment is unlikely to be used more generally because the risks from transplants are high. Durand says that Johns Hopkins is now revising its transplant procedures to keep people with both cancer and HIV on antiretroviral drugs during the transplant regimen.

Separately, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, based in Silver Spring, Maryland, is trying to replicate the Berlin patient’s cure by giving CCR5-mutated HIV-resistant blood from umbilical cords to children and adults with HIV and cancer.

Everyone with HIV could benefit from this work, researchers say, because it could yield valuable information about how to eliminate the HIV reservoir.

“We are still a long way off from a viable cure option for most patients,” Durand says. “But every step counts, and these cases can teach us important lessons.”

Nature doi:10.1038/nature.2013.13297

Source

High SVR rates with DAA regimen among chronic HCV patients

Provided by Healio

July 5, 2013

Sustained virologic response to a regimen of three antivirals and ribavirin was highly prevalent with or without a ribavirin dose reduction among patients with chronic HCV in a study presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated 247 noncirrhotic patients with chronic HCV genotype 1, including 159 treatment-naive patients and 88 who were nonresponsive to previous interferon-based therapy. Patients were assigned 12 or 24 weeks of treatment with a combination of three direct-acting antivirals (DAA): HCV protease inhibitor ABT-450/r; NS5A inhibitor ABT-267, and non-nucleoside NS5B inhibitor ABT-333, along with weight-based ribavirin (RBV).

Four patients discontinued treatment due to adverse treatment-related events, and one patient experienced arthralgia considered potentially related to the regimen. Hemoglobin levels below 10 g/dL were measured in 16 patients during therapy, with one patient indicating levels below 8.5 g/dL.

RBV dose reductions were required due to toxicity in 27 cases, including 21 treatment-naive patients and six prior null responders. The most frequent adverse event requiring RBV reduction was anemia, which occurred in 16 cases. Other events resulting in dose reduction included diarrhea, fatigue, dizziness and increased creatinine levels.

After 12 weeks post-treatment, sustained virologic response (SVR) was observed in all participants who required an RBV reduction, as well as 93.5% of treatment-naive patients and 92.7% prior null responders who did not receive a dose reduction.

“RBV dose reductions were required less frequently with this peginterferon-free regimen than in previously reported studies of subjects receiving peginterferon-containing regimens,” the researchers wrote. “High SVR12 rates (100%) were achieved among subjects requiring RBV dose reduction.”

For more information:

Cohen D. TUAB0103: Safety of Ribavirin-Containing Regimens of ABT-450/r, ABT-333 and ABT-267 for the Treatment of HCV Genotype 1 Infection and Efficacy in Subjects with Ribavirin Dose Reductions. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Closing the HIV Treatment Gap: A Global Development Priority

Provided by The Huffington Post

Ray Chambers and Dr. Margaret Chan

Posted: 07/03/2013 12:20 pm

Every movement has its moments. The quest to defeat HIV has had more than its share, both exhilarating and devastating. Yet through it all, the global community has come together in the most positive ways: Researchers remained undeterred. Advocates were indefatigable. Leaders chose to prioritize HIV, not ignore it. Patients bravely refused to succumb to resignation. Today, we have the knowledge and tools to send the HIV epidemic into irreversible decline. The key is getting everyone living with HIV, who is eligible for treatment, on antiretroviral drugs (ARVs), as soon as we possibly can.

This week in Kuala Lumpur the World Health Organization (WHO) announced its new Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection, a document whose long descriptive title belies the extraordinary developments it relays. In a nutshell, the document recommends a major stepping up of HIV treatment with proven drugs. And in doing so, it lays the path for a quantum leap ahead in bringing the epidemic under control.

We are at a tipping point in the fight against AIDS. The evidence is overwhelming that antiretroviral drugs (ARVs) work, and work powerfully. They prolong and save lives. They make people living with HIV healthier and bring security to affected families. As ARVs lower the amount of virus in the body, the likelihood of HIV transmission also plummets. This means people with HIV on ARVs are far less likely to transmit the virus to others. Not only are sexual and drug-using partners protected. When pregnant women with HIV are placed on ARVs, this prevents virus transmission to the child - a successful intervention that has allowed the 22 highest-burden countries to report a 38-percent decline in mother-to-child transmission of HIV since 2009.

With this knowledge in hand, WHO is recommending earlier initiation of treatment for people with HIV, raising the "CD4 count" threshold that would qualify a person for treatment from 350 to 500 (the CD4 count is a key indicator of the strength of the immune system - the higher the count the stronger the immune system). By getting more people on treatment earlier, we will save lives, make people healthier and reduce virus transmission to others. WHO's recommendations translate into an increase in the number of people eligible for antiretroviral therapy, from nearly 17 million to 26 million. This means treating adults, adolescents and children earlier in the disease cycle, as well as immediately treating all pregnant and breastfeeding women and certain populations with other conditions, such as tuberculosis and hepatitis B liver disease.

If countries fully implement these recommendations, it is estimated that we would save an additional three million lives and prevent an additional 3.5 million infections - from 19 down to 15.5 million - between 2013 and 2025, over and above those saved by the current WHO guidelines.

Some 10 million people are now receiving ARV therapy (ART). This signals incredible progress over the last ten years: in 2002 only about 300,000 persons in low-income and middle-income countries were able to access lifesaving treatment. The challenge now is to move from 10 million to 26 million people covered. To do so we must make meeting this challenge a global priority. We must enable everyone who is at risk to get tested, and we must act proactively to ensure that those who are eligible for treatment are provided with an opportunity to begin ART as soon as possible. There is money to get the job done, but unlocking and focusing funds requires an acknowledgement that ART is a critical path in the HIV response, complementing already proven HIV prevention strategies.

Game-changing recommendations like this are best when all stakeholders are engaged in the process. For this reason, WHO developed these guidelines in consultation with people living with HIV, representatives of country programs from all affected regions, civil society thought leaders, technical experts, implementing partners, development agencies and key UN agencies.

Sending the HIV epidemic into a tailspin is a long-sought dream. Making it a reality requires the kind of bold action that WHO, and the many experts that advise this agency, are guiding the world to take.

Raymond Chambers, UN Secretary-General's Special Envoy for Financing the Health Millennium Development Goals and for Malaria

Dr. Margaret Chan, Director-General, World Health Organization

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Two Patients HIV-Free after Stem Cell Treatment

Published: Jul 3, 2013

By Michael Smith, North American Correspondent, MedPage Today

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Note that researchers have demonstrated that two men with HIV who received a bone marrow transplant were able to stop anti-retroviral therapy without viral rebound.
• Be aware that bone marrow transplant is too risky a strategy to broadly employ in the treatment of HIV.

KUALA LUMPUR -- Two HIV-positive men who got a stem cell transplant to treat blood cancers have now been off antiretroviral drugs for several weeks without evidence of the virus rebounding, a researcher said here.

The apparent HIV remissions are exciting developments, but it is too early to say the men have been cured, according to Timothy Henrich, MD, of Brigham and Women's Hospital in Boston.

"It is possible that the virus could come back next week," Henrich told reporters before his late-breaker presentation at the 7th International AIDS Society meeting on HIV pathogenesis, treatment, and prevention.

But researchers have been unable to find evidence of HIV replication or of HIV DNA integrated into inactive immune cells, although the men have been off HIV therapy for 8 and 15 weeks, respectively, Henrich reported.

If that state persists, he said, it might offer clues to a more widely applicable approach to inducing HIV remission, since stem cell transplant is "not a practical strategy" to cure the 34 million people with HIV worldwide.

Outside experts also cautioned against hyping the findings.

"The next step is to confirm this in larger numbers," said Sharon Lewin, MD, of Monash University in Melbourne, Australia. That might be possible because stem cell transplants are performed relatively often around the world, some of them in people with HIV.

But she echoed Henrich's view that stem cell transplant will not be widely useful in curing HIV, if only because of the expense and risk of the procedure.

But, she told reporters, such cases are "absolutely instrumental in moving the science forward."

Indeed, Henrich said, so far investigators don't know what aspect of the stem cell transplant and subsequent therapy led to the disappearance of the virus.

The best guess at the moment, Henrich said, is that graft-versus-host disease -- a common sequel to allogeneic stem cell transplant -- eliminated HIV-bearing host cells while the donor cells were protected from infection by antiretroviral therapy.

The finding is reminiscent of the case of Timothy Brown, the "Berlin patient," who was the first person to have an apparently curative stem cell transplant.

But in that case, doctors sought a donor whose immune cells carried a mutation -- the delta32 variant of the CCR5 gene -- that rendered them resistant to HIV infection.

Brown had what is called myoablative conditioning to completely destroy his own immune system before getting the donor cells and was not on antiretroviral drugs after the transplant.

In the 2 cases in Boston, both men had minimal conditioning with chemotherapeutic drugs, so their own immune systems were not completely destroyed. And they got donor cells that -- in principle -- were susceptible to HIV.

During and after the transplant, both patients remained on antiretroviral therapy for 2.7 and 4.5 years of follow-up before stopping therapy, Henrich said.

It was only recently -- after consultation with ethics boards, the patients themselves, and their doctors -- that Henrich and colleagues "felt justified" in stopping the anti-HIV medications.

The decision to undertake an "analytical treatment interruption" was based on the continuing inability to find HIV in the two men, Henrich said.

Because of the effectiveness of current anti-HIV therapy, the investigators thought stopping treatment entailed "minimal risk" to the patients, senior investigator Dan Kuritzkes, MD, also of Brigham and Women's, told MedPage Today.

Such treatment interruptions have been tested several times in patients who have suppressed virus under anti-retroviral therapy, and usually result in HIV rebound within days.

But there are several cases -- including a cohort in France -- where such interruptions have led to durable control of the virus without the need to resume anti-HIV therapy.

And U.S. researchers are following up the case of an HIV-positive infant, treated within hours of birth, who currently has no evidence of the virus although she was lost to follow-up and did not receive treatment for several months.

In the months and years to come, Lewin said, it's extremely likely that more such individual cases of HIV remission will be found, which might raise "false hope" for a cure.

"We want a much larger, scalable cure" to treat 34 million people, she said, "and that is going to be quite a challenge."

The study was supported by the NIH, Amfar, and the Bill and Melinda Gates Foundation. Henrich has previously reported financial links with Bristol-Myers Squibb.

Primary source: International AIDS Society
Source reference:
Henrich T, et al. "In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation" IAS 2013; Abstract WELBA05.

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