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HIV/HCV Coinfection

IAS 2015: Fatty Liver May Contribute to Higher Risk of Death for HIV/HCV Coinfected People

About a quarter of HIV and hepatitis C virus (HCV) coinfected people in a New York City cohort died over a 10-year follow-up period -- a "strikingly low" survival rate -- according to a poster presented at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention last month in Vancouver. Researchers saw trends toward an association between steatosis (fatty liver) and cardiovascular disease, diabetes, and overall survival.

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IAS 2015: Accessing Hepatitis C Treatment [VIDEO]

While new interferon-free direct-acting antiviral therapy can cure more than 90% of people with chronic hepatitis C -- including those with HIV/HCV coinfection -- access to treatment remains a major challenge, experts said at a media briefing on HIV and hepatitis coinfection at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention last month in Vancouver.

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Do Sex and HIV/HCV Coinfection Affect Response to Antiretroviral Treatment?

HIV-positive men and women coinfected with hepatitis C virus (HCV) showed impaired CD4 T-cell restoration after starting antiretroviral therapy (ART) and had a 40% greater risk of death than people with HIV alone, though they were equally likely to achieve HIV viral suppression, according to study findings published in the May 18 advance edition of AIDS Patient Care and STDs.

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IAS 2015: PrEP and the Risk of Hepatitis C Virus Infection [VIDEO]

 Are gay and bisexual men who take Truvada for HIV pre-exposure prophylaxis (PrEP) at greater risk for sexually transmitted hepatitis C virus (HCV) infection? Experts discussed this issue and others at a media briefing on HIV and hepatitis coinfection at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention last month in Vancouver.

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CROI 2015: HCV Sexual Transmission Linked to Anal Sex, Drug Use, Lower CD4 Count

In addition to the usual risk factors for hepatitis C virus (HCV) sexual transmission seen in most previous studies -- such as anal sex and having other sexually transmitted infections -- researchers in the Netherlands also saw an association with nasal and injection drug use and lower CD4 T-cell count, they reported in a poster presentation at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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IAS 2015: Daclatasvir + Sofosbuvir Cures Most Coinfected People in French Compassionate Use Study

 Interferon-free treatment using daclatasvir (Daklinza) and sofosbuvir (Sovaldi), with or without ribavirin, was well-tolerated and produced sustained virological response rates of 95%-100% for HIV/HCV coinfected people with advanced liver disease, according to a presentation at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) last month in Vancouver. These results, from a French program that provides new drugs to patients in need of treatment prior to regulatory approval, demonstrate that outcomes in the "real world" can be as good as those seen in clinical trials of the new drugs.

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CROI 2015: End-Stage Liver Disease Among HIV+ People with Hepatitis B or C

People coinfected with HIV and hepatitis B or C virus are more likely to progress to end-stage liver disease, or liver failure, compared to those with HIV alone, and individuals triply infected with all 3 viruses are at greatest risk, according to study findings presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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IAS 2015: Interferon-free Hepatitis Treatment Highly Effective for HIV/HCV Coinfected People

A trio of interferon-free regimens -- sofosbuvir/ledipasvir, AbbVie's 3D regimen, and grazoprevir/elbasvir -- were well-tolerated and cured more than 90% of HIV/HCV coinfected participants in 3 clinical trials, confirming that HIV-positive people can respond as well as HIV-negative people to modern hepatitis C treatment, according to a set of reports presented at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) last week in Vancouver.

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CROI 2015: Re-infection Due to Ongoing Risk Is Probably the Cause of HCV Recurrence After SVR

Rates of hepatitis C virus (HCV) recurrence after successful therapy differ markedly between risk groups, according to the results of a meta-analysis presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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IAS 2015: Effective New Treatment for HIV/HVC Coinfection [VIDEO]

Jürgen Rockstroh from the University of Bonn presented an overview of HIV/HCV coinfection during a press briefing at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention last week in Vancouver. Rockstroh covered topics including faster fibrosis progression and effective interferon-free therapy for coinfected people.

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CROI 2015: Sustained Virological Response Represents a Long-term Cure for Hepatitis C

Almost all patients with hepatitis C virus alone or HIV/HCV coinfection who achieved sustained virological response (SVR) to treatment with sofosbuvir (Sovaldi) plus ribavirin or sofosbuvir/ledipasvir (Harvoni) still had undetectable HCV RNA up to 2.4 years later, confirming that SVR represents a cure, according to a poster presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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IAS 2015: Access to Screening and Treatment Are Key Issues for Hepatitis B and C

The development of effective new interferon-free treatment makes it possible to cure more than 90% of people with chronic hepatitis C, including most people with HIV/HCV coinfection, researchers said at the 2nd International HIV/Viral Hepatitis Co-infection Meeting, preceding the 8th International AIDS Society Conference (IAS 2015) taking place this week in Vancouver. Looking at hepatitis B, antiviral therapy can effectively suppress the virus long-term, but most people are still not cured.

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CROI 2015: Sofosbuvir/Ledipasvir May Alter Antiretroviral Levels in HIV/HCV Coinfected People

HIV/HCV coinfected people who take sofosbuvir/ledipasvir (Harvoni) to treat hepatitis C along with boosted protease inhibitor antiretroviral regimens may experience changes in drugs levels, but these are mostly not considered clinically relevant, according to a drug-drug interaction study presented at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) last month in Seattle. However, data on the safety and efficacy of combining sofosbuvir/ledipasvir and boosted protease inhibitors during treatment are lacking, and increased tenofovir exposure may be a concern.

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IAS 2015: International AIDS Society Conference Starts this Weekend in Vancouver

The 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) starts this Sunday and runs July 19-22 in Vancouver. HIV prevention -- including treatment-as-prevention and pre-exposure prophylaxis (PrEP) -- will be a major focus of the meeting. Other topics will include antiretroviral drugs in development, expanding access to treatment and retention in care, and HIV/hepatitis coinfection. HIVandHepatitis.com will be on site covering the latest news.

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CROI 2015: Hepatitis C -- Mission Accomplished? [VIDEO]

New interferon-free treatment for hepatitis C virus (HCV) has brought about a revolution in treatment, but challenges still remain -- among them too few people with HCV being diagnosed and the high cost of the new drugs -- before the mission can be declared a success. A panel of hepatitis C experts discuss research presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections(CROI) in Seattle with HIVandHepatitis.com editor Liz Highleyman in this IFARA video.

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HIV/HCV Coinfected People with Moderate or Worse Fibrosis at Risk for Liver-Related Death

HIV-positive people coinfected with hepatitis C virus (HCV) are more likely to die of liver-related causes if they have moderate or worse fibrosis or cirrhosis, and they should therefore be prioritized for the new antiviral treatment, according to a study described in the June 19 edition of AIDS.

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CROI 2015: Deferring Hepatitis C Treatment Can Lead to Liver Cancer and Death

HIV/HCV coinfected people who delay hepatitis C treatment remain at risk for liver failure, hepatocellular carcinoma and liver-related death even after being cured -- with outcomes worsening the longer it is put off -- indicating that treatment should not be deferred until advanced disease, according to a presentation at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) last week in Seattle. Treating only after progression to cirrhosis increased the risk of liver-related death by more than 5-fold and the duration of infectiousness by 4-fold.

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Coverage of the 2015 International AIDS Society Conference

HIVandHepatitis.com coverage of the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015), July 19-22, in Vancouver, Canada.

Conference highlights include HIV treatment as prevention, pre-exposure prophylaxis (PrEP), new antiretroviral therapies, HIV cure research, hepatitis C and HIV/HCV coinfection, and global scale-up of prevention and treatment.

Full listing by topic

IAS 2015 website

7/22/15

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Coverage of the 2015 Conference on Retroviruses and Opportunistic Infections

HIVandHepatitis.com coverage of the 2015 Conference on Retroviruses and Opportunistic infections (CROI 2015), February 23-26, 2015, in Seattle.

Conference highlights include PrEP and HIV treatment as prevention, hepatitis C treatment for HIV/HCV coinfected people, new antiretroviral drugs, HIV cure research, HIV-related conditions, TB, Ebola virus, and access to care.

HIVandHepatitis.com coverage by topic

CROI website

3/2/15

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Injection Drug Use and Hepatitis C Coinfection Increase Risk of Death for People with HIV

HIV-positive people who inject drugs and those who are coinfected with hepatitis C virus (HCV) have elevated mortality rates, according to a report from the ART Cohort Collaboration published in the July 1 Journal of Acquired Immune Deficiency Syndromes. HIV/HCV coinfected drug injectors had a high risk of liver-related death, but those without HCV still had higher mortality due to various causes compared with non-injectors.

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CROI 2015: Interferon-Free Regimens Show High Cure Rates for HIV/HCV Coinfected

A pair of 2-drug, 12-week regimens containing neither interferon nor ribavirin -- sofosbuvir (Sovaldi) plus either ledipasvir (the Harvoni coformulation) or daclatasvir (Daklinza) -- cured 96% of HIV/HCV coinfected people with various hepatitis C genotypes, according to presentations at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) this week in Seattle. These findings confirm that hepatitis C patients with HIV can be treated the same as those with HCV alone.

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The advent of oral direct-acting antiviral agents (DAAs) that target different steps of the hepatitis C virus (HCV) lifecycle has revolutionized treatment, offering therapy that is shorter, better tolerated and more effective than interferon-based treatment. This is particularly beneficial for HIV/HCV coinfected people who tend to have more rapid liver disease progression and do not respond as well to interferon.

Sofosbuvir/Ledipasvir

Susanna Naggie from Duke Clinical Research Institute in North Carolina presented results from ION-4, a Phase 3 trial evaluating the safety and efficacy of Gilead Science's nucleotide HCV NS5B polymerase inhibitor sofosbuvir plus NS5A inhibitor ledipasvir in HIV/HCV coinfected patients.

Results from ION-1 (genotype 1 treatment-naive, 12 vs 24 weeks), ION-2 (genotype 1 prior non-responders, 12 vs 24 weeks) and ION-3 (genotype 1 treatment naive, 8 vs 12 weeks) were presented previously, showing that sofosbuvir/ledipasvir cured 95% or more of HCV monoinfected people.

ION-4 study enrolled 335 coinfected participants in the U.S., Canada, and New Zealand. The trial had broad inclusion criteria and included more difficult-to-treat groups such as prior non-responders and people with liver cirrhosis.

Most participants (82%) were men, 34% were black -- far more than in most DAA trials to date -- and the mean age was 52 years. Almost all (98%) had HCV genotype 1, with a small number of genotype 4s. More than half (55%) were treatment-experienced, three-quarters had unfavorable IL28B gene variants, and 20% had compensated cirrhosis.

With regard to HIV, the participants were on antiretroviral therapy (ART) and most had undetectable HIV viral load. They could be taking either efavirenz (Sustiva, 48%), raltegravir (Isentress, 44%), or rilpivirine (Edurant, 9%), all with tenofovir/emtricitabine (Truvada).

All participants in this open-label study received 400 mg sofosbuvir plus 90 mg ledipasvir, taken as a once-daily coformulation, for 12 weeks. They were followed for an additional 12 weeks after completing treatment to assess sustained virological response (SVR12), or continued undetectable HCV RNA.

Results

  • The overall SVR12 rate in this study was 96%, similar to rates seen in the ION HCV monoinfection studies.
  • Rates were very similar for treatment naive and treatment-experienced patients (95% and 97%), and for people with and without cirrhosis (94% and 96%).
  • The 20% of patients who were found to have NS5A resistance-associated variants at baseline had a 94% cure rate (no NS5B resistant variants were detected).
  • 10 people relapsed after the end of treatment, 2 experienced treatment failure due to poor adherence, 1 was lost to follow-up, and 1 died of a presumed unrelated cause.
  • In a multivariate analysis the only factor that significantly predicted relapse was black race/ethnicity -- in fact, all 10 relapsers were black.
  • Sofosbuvir/ledipasvir was generally safe and well-tolerated.
  • There were 2 serious adverse events due to advanced liver disease and 1 death, but no treatment discontinuations due to adverse events.
  • The most common side effects were headache (25%), fatigue (21%), diarrhea (11%), and nausea (10%).
  • Participants maintained stable CD4 counts and none had confirmed HIV rebound.
  • Because they were taking tenofovir, their kidney function was carefully monitored; 4 patients (1%) had small creatinine increases, of whom 2 completed HCV treatment with no regimen change, 1 reduced their tenofovir dose, and 1 stopped tenofovir.

Naggie noted that the racial disparity in treatment failure rates was not seen in the ION monoinfection trials, in which 99% of black patients were cured, but their numbers may have been too small to see an effect. The researchers have not determined why this was the case, but further analysis including genetic sequencing and genome-wide association studies are underway.

Sofosbuvir + Daclatasvir

David Wyles from the University of California at San Diego presented results from the ALLY-2 trial looking at sofosbuvir in combination with a different NS5A inhibitor, Bristol-Myers Squibb's daclatasvir. Daclatasvir is available in Europe and Japan, and is currently awaiting U.S. Food and Drug Administration approval.

The sofosbuvir plus daclatasvir combination performed well in early studies, but Gilead decided to halt development of this regimen in order to focus on its own NS5A drug, ledipasvir. Once sofosbuvir was approved and on the market, however, Bristol-Myers was able to move forward with Phase 3 clinical trials.

ALLY-1 tested the sofosbuvir plus daclatasvir regimen with ribavirin for 12 weeks in patients with cirrhosis or liver transplant recipients with HCV genotypes 1-6, ALLY-2 tested sofosbuvir plus daclatasvir without ribavirin for 8 or 12 weeks in HIV/HCV coinfected people with HCV genotypes 1-6, and ALLY-3 tested the combination for 12 weeks in patients with genotype 3.

An advantage of daclatasvir is that it is active against multiple HCV genotypes (known as "pangenotypic") while ledipasvir is primarily active against genotype 1. This is important because while genotype 1 is most common in the U.S. and Europe, different genotypes predominate in other countries with high hepatitis C burdens.

All participants in ALLY-2 received once-daily 400 mg sofosbuvir plus daclatasvir. ALLY-2 enrolled 2 cohorts: 151 previously untreated patients (including prior use of sofosbuvir) who received the regimen for 8 or 12 weeks, and 52 treatment-experienced patients all of whom received the 12-week course.

Overall, nearly 90% were men, about 60% were white, about 35% were black, and the median age was approximately 55 years. A majority (63%-70% across treatment arms) had harder-to-treat HCV subtype 1a, 12%-21% had subtype 1b, 4%-12% had genotype 2, 6%-8% had genotype 3, and 0%-4% had genotype 4. About 10% of treatment-naive patients had cirrhosis, rising to 29% for the treatment-experienced group.

Participants could either be on ART with undetectable HIV RNA and a CD4 count of at least 100 cells/mm3, or not yet on ART with at least 350 cells/mm3. Median CD4 counts were in the 500-600 cells/mm3 range. Those on ART were permitted to take a wide range of antiretrovirals. The standard 60 mg daclatasvir dose was adjusted down to 30 mg with ritonavir-boosted HIV protease inhibitors or up to 90 mg with most NNRTIs to account for drug interactions (all doses were combined in the analysis).

Results

  • SVR12 rates were high in the 12-week arms: 96% for treatment-naive patients and 98% for treatment-experienced.
  • The cure rate fell to just 76%, however, for treatment-naive people who took only 8 weeks.
  • These rates were nearly the same whether looking at just genotype 1 patients or all genotypes together.
  • There was 1 relapse in both of the 12-week arms, but 10 in the 8-week arm.
  • Both relapsers treated for 12 weeks had HCV 1a; everyone with genotypes 2, 3 or 4 treated for this duration were cured. 
  • People with cirrhosis had lower cure rates than non-cirrhotics in both the 8-week arm (60% vs 77%) and in the naive (89% vs 99%) and experienced (93% vs 100%) 12-week arms.
  • In the 8-week arm SVR12 rates also varied by ART regimen, with those taking darunavir/ritonavir (Prezista) doing worse; there was no difference, however, in the 12-week arms. Wyles suggested this might be due to sub-therapeutic drug levels, as ritonavir did not boost daclatasvir as much as expected.
  • Here too, treatment was generally safe and well-tolerated.
  • There were no deaths or adverse events leading to treatment discontinuation, and serious adverse events were uncommon (0%-3%).
  • Most patients maintained HIV viral suppression and stable CD4 counts.

Speaking at a CROI press conference, both Naggie and Wyles noted that their studies saw response rates in these HIV/HCV coinfected patients as high as those for HCV monoinfected people in prior trials. This supports recent hepatitis C treatment guidelines recommending that HIV positive and negative people should be treated the same for hepatitis C, with the exception of taking into account interactions with antiretrovirals.

"These are really exceptional cure rates and they are very safe regimens," Naggie said. "ION-4 and ALLY-2 offer great options for people who are coinfected."

It remains unclear how sofosbuvir plus daclatasvir will be used in clinical practice, given the availability of Harvoni. The difference between the full (non-discounted) U.S. cost of sofosbuvir alone and Harvoni for 12 weeks is about US$10,500 -- likely less than the eventual price of daclatasvir. However, the relative cost and availability of specific drugs varies from country to country. Wyles suggested that it may be beneficial, especially for coinfected patients, to use 2 separate pills rather than a coformulation so that drug doses can be adjusted independently.

Daclatasvir appears to be active against a wider range of HCV genotypes than ledipasvir, though press conference moderator David Thomas from Johns Hopkins suggested that there have been too few patients with other genotypes in clinical trials to get definitive answers. Genotype 3 patients with cirrhosis remain a difficult-to-treat population. Gilead is working on a new coformulation of sofosbuvir and a next-generation NS5A inhibitor with pangenotypic activity (GS-5816).

2/27/15

References

D Wyles, P Ruane, M Sulkowski, et al. Daclatasvir in Combination With Sofosbuvir for HIV/HCV Coinfection: ALLY-2 Study
. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 151LB.

S Naggie, C Cooper, MS Saag, et al. Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected With HCV and HIV-1. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 152LB.