Brandon May

 (HCV) genotype 2 and genotype 3, treatment regimens comprised of daclatasvir plus sofosbuvir plus ribavirin (DCV+SOF±RBV) and velpatasvir/sofosbuvir (VEL/SOF) plus RBV confer similar efficacy profiles in terms of achieving a cure, according to a new study.

Predictors for sustained virologic response (SVR) in genotype 3 patients treated with these regimens, according to the researchers, include prior HCV treatment, FIB-4 >3.25, and history of decompensated liver disease.

“Given the size of the cohort, we were able to discern differences among these treatment regimens which are widely used throughout the world, particularly among treatment-experienced patients, thus providing germane information on their effectiveness in genotype 2 and genotype 3 populations to better inform HCV management strategies,” leading study author, Lisa Backus, MD, PhD, told 

®. “We believe these findings are relevant to an extensive audience, including environments where wide access to all regimens are not readily available.”

Backus noted that, while DCV+SOF is not widely used in the US, investigators found it is as effective as VEL/SOF in difficult-to-treat subgroups.

For this observational study, investigators evaluated the effectiveness of DCV+SOF±RBV or VEL/SOF±RBV between patients with genotype 2 and genotype 3 HCV patients receiving care at the Department of Veterans Affairs. Specified analyses were focused on patients receiving DCV+SOF (n = 255), VEL/SOF (n = 2230), DCV+SOF+RBV (n= 42), and VEL/SOF+RBV (n= 247).

In patients with HCV genotype 2, there were no differences in regard to SVRs in patients receiving DCV+SOF and VEL/SOF (94.5% vs 94.4%; 

= .94) or between DCV+SOF+RBV and VEL/SOF+RBV (88.1% vs 89.5%; 

= 1.00). Additionally, there were no differences among HCV genotype 3 patients in terms of the SVR between regimens comprised of DCV+SOF and VEL/SOF (90.8% vs 92.0%; 

= .50) or DCV+SOF+RBV and VEL/SOF+RBV (88.1% vs 86.4%, respectively; 

There was no significant predictive effect of any treatment regimen for predicting the odds of SVR in either genotype 2 or genotype 3 patients. In genotype 3 patients, however, significant predictors associated with a decreased SVR odds included prior HCV treatment (odds ratio [OR] 0.51; 95% CI: 0.36 - 0.72; 

< .001), FIB-4 >3.25 (OR 0.60; 95% CI: 0.43 - 0.84; 

= .002), and a history of decompensated liver disease (OR 0.68; 95% CI: 0.47 - 0.98; 

“Because of the timeframe of this study, some regimens that were used were not a part of current HCV guideline recommendations as guidelines were either not updated at the time these patients were initiating treatment (mid 2015 to early 2017) because of the rapidity of emerging data or because guideline recommendations have since changed,” Backus explained.

As such, he stressed the importance of remember real-world providers may make decisions to extend treatment, add ribavirin, or use non-approved combinations.

Backus added that future research studies should focus on evaluating such outcomes with non-traditional regimens as potential therapy alternatives, particularly given the limited HCV drug pipeline.

“As new data emerges with expanded use of HCV antiviral agents. it is important to consider real-world data when updating HCV treatment guidelines, recognizing that inevitably not all patients will be treated as recommended in guidelines,” Backus said.

The study, "Real-world Effectiveness of Daclatasvir plus Sofosbuvir and Velpatasvir/Sofosbuvir in Hepatitis C Genotype 2 and 3," was published online in the 

This article was originally published by 

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Treatment regimens consisting of daclatasvir plus sofosbuvir plus ribavirin and velpatasvir/sofosbuvir plus ribavirin show similar cure rates in patients with hepatitis C virus genotype 2 and 3.


Hepatitis C Combinations Show Similar Efficacy Profiles in Genotypes 2, 3

Investigators have targeted a new source for hepatitis C (HCV) treatment analysis—a source with relevant data in the era of direct-acting antiviral (DAA) therapy.

The national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) is a resource with accurate data on DAA use for chronic HCV treatment, making this data source a reliable base from which researchers can create retrospective analyses, according to a new study.

As a result, this observational data could serve an important role in pharmacoepidemiologic studies that would assess the overall benefit and risks of modern HCV therapies, investigators, led by Christopher T. Rentsch, MPH, noted. The CDW is a national source of documented prescriptions and pharmacy fills. In contrast, electronic data from each VA facility going through multiple extracts, transforms, and loads—meaning original data validity could be compromised.

Investigators retrospectively assessed HCV-infected patients treated with DAAs who were included in the Veterans Aging Cohort Study (VACS) at 5 different VA treatment sites (n = 501). All patients had pharmacy fill data available for analysis. The range of DAA agents or regimens prescribed in the cohort were as follows:

		Ombitasvir/ paritaprevir/ ritonavir/ dasabuvir

The researchers also randomly selected patients with chronic HCV infection who were not treated for HCV during the 2-year study period. These patients underwent chart review. Study investigators calculated the positive predictive and negative predictive values overall and by VA treatment site.

Out of 2416 prescriptions recorded for the overall cohort, only 494 were validated based on data from the CDW approximately 6 months following the study period. This validation resulted in a positive predictive value of 98.6% (95% CI: 97.6 - 99.6). Across all 5 treatment sites, the positive predictive values featured a range of 96.7% to 100% (

In 100 HCV patients in the CDW who did not receive HCV treatment, approximately 97% (n = 97) had confirmation of non-treatment, whereas 3% (n = 3) did receive HCV treatment during the 2-year study period. These findings resulted in an overall negative predictive value of 97.0% (95% CI: 93.7 - 100), which were comparable across all treatment sites (

In data extraction 6 months after the main study period, only 1 out of 22 prescriptions were found for 3 patients who had no records of treatment recorded in the CDW. This finding yielded an updated positive predictive value of 98.6% (95% CI: 97.6 - 99.6) as well as a negative predictive value of 99.0% (95% CI: 97.1 - 100).

The analysis of patients attending only 5 VA sites may have resulted in findings that lack generalizability across all VA centers. Additionally, the retrospective nature of the study was a potential limitation of the analysis.

That said, observational data could still play an important role in safety- and efficacy-based assessments of modern HCV therapies.

“These findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information, particularly after a 6-month lag for data extraction, on HCV therapies in the modern treatment era, even for VA patients who obtained treatment from non-VA providers,” investigators wrote.

Assessing comparative effectiveness of several different DAA regimens, the importance of adverse effects (eg, acute liver injury or HBV reactivation), and the effect of alcohol abuse on DAA receipt with treatment outcomes may be an important future area of research, investigators concluded.

Provider verification of electronic health record receipt and nonreceipt of direct-acting antivirals for the treatment of hepatitis C virus infection

The national Veterans Health Administration Corporate Data Warehouse could be key in revealing accurate data on the use of direct-acting antivirals in the treatment of chronic hepatitis C virus.

VA Data Could Prove Key in Assessing Real-World Efficacy of Hepatitis C Drugs

In a study of chronic hepatitis C virus patients with compensated liver cirrhosis, sofosbuvir, a direct-acting antiviral (DAA) nucleotide analog inhibitor of the viral NS5B protein, was effective for achieving a sustained virologic response (SVR) in the majority of patients in a community care setting. The study was led by researcher Vijay Gayam, MD, of the Interfaith Medical Center in Brooklyn, New York.

“Successful treatment of chronic [hepatitis C virus infection], also described as a sustained virological response (SVR), is defined as an absence of detectable hepatitis C virus RNA 12 weeks after the completion of treatment. [Chronic hepatitis C] patients who achieve SVR have both lower rates of complications and lower overall mortality,” the investigators wrote. “Until recently, chronic [hepatitis C virus] treatment was primarily based on interferon-based regimens, but disappointing response rates, particularly amongst patients with advanced liver disease, necessitated the need for a new regimen.”

A total of 112 patients with chronic hepatitis C virus and compensated liver cirrhosis who received 12 weeks or more of combination hepatitis C virus treatment in a community clinic were included in the retrospective analysis. Combination regimens included either 90 mg/day of ledipasvir (LDV) plus 400 mg/day of sofosbuvir (SOF) ± 1000 mg/day (for <75 kg) (n = 87) or 1200 mg/day (for ≥75 kg) ribavirin (RBV) or 400 mg/day SOF plus 100 mg/day velpatasvir (VEL) (n = 25). Treatment durations were either 12 weeks (n = 98) or 24 weeks (n = 14).

The investigators assessed the safety and tolerability of therapies by retrospectively reviewing adverse events, treatment completion, dosage reductions, and medication discontinuation. Additionally, they compared pre- and post-treatment patient characteristics as well as treatment efficacy and 12-week SVR (SVR12). An undetectable viral load at 12-week follow-up comprised the SVR12. Response to therapy was evaluated using HCV RNA viral load (IU/mL) at 4-week intervals, following treatment completion, and 12 weeks after treatment.

On average, approximately 90% of patients who were treated with the DAA combination regimens achieved SVR12. In the LDV/SOF arm, 89.7% achieved SVR12, whereas 92% of patients in the SOF/VEL group achieved SVR12.

Study establishes real-world efficacy, tolerability, and safety profile of sofosbuvir-based regimens in patients with chronic hepatitis C who have compensated liver cirrhosis.

Sofosbuvir Achieves Sustained Virologic Response in HCV Patients With Cirrhosis

Testing for respiratory syncytial virus (RSV) infection during the influenza season is uncommon among pregnant mothers, and a slightly high proportion of tests that are performed often result in a misdiagnosis, according to a study in Clinical Infectious Diseases.

Additionally, the researchers found an association between RSV-positivity and pre-term delivery as well as a high rate of asthma in RSV women with pre-existing conditions.

“While we know RSV is a major cause of severe respiratory infections in young children, relatively less is known about RSV infection in adults,” study researcher Annette Regan, PhD, MPH, of Curtin University in Bentley, Western Australia, told Contagion®. “We found that women were not commonly hospitalized with RSV during pregnancy; however, when they were, these infections could be severe, which may mean that strategies which can prevent these infections would have value.”

Researchers identified 1,604,206 pregnant women in Western Australia, California, Ontario, and Israel who were admitted to a total of 4 clinical sites for an acute respiratory infection or febrile illness. Pregnancy data were linked with laboratory testing and hospital discharge data. Patients were tested for RSV during the influenza seasons. The investigators obtained data on hospital admission, the results of the RSV tests, hospital length of stay, and birth outcomes.

In the study cohort, the incidence rate of hospitalizations related to an acute respiratory infection or febrile illness was 0.9% (n = 15,287). Among these patients, approximately 6% (n = 846) of pregnant women received a test for RSV. When tests used reverse transcription polymerase chain reaction, 2.5% (n = 21) of women were found to have a positive RSV diagnosis, with an observed incidence range of 1.9% in Ontario to 3.1% in Israel. Additionally, the positivity percentage ranged from 0% to 4.0% in 2011 to 2012 and 2013 to 2014, respectively. Only <1% of women who were tested for influenza received a positive diagnosis for both RSV and influenza.

A slight majority of testing and detections of RSV occurred later in pregnancy (63% and 67%, respectively), particularly in the third trimester. In the 38% of RSV-positive women with a pre-existing health condition, asthma was the most frequently reported condition (19%). Compared with RSV-negative women, a diagnosis of pneumonia was more frequent among RSV-positive women (19% vs 38%, respectively; P =.046), demonstrating that misdiagnosis may be common in these patients. In addition, the researchers also found a significant association between an RSV-positive diagnosis and pre-term birth compared with RSV-negative diagnoses (29% vs 15%, respectively; P =.034).

“This study helps us better understand severe RSV infection during pregnancy,” Dr. Regan explained. “An RSV vaccine is currently in advanced stages of clinical development, which is meant to be administered during pregnancy in order to protect infants in the first few months of life. Our results suggest that in addition to the benefits of vaccination to the infant, there may be some additional benefit to the mother.”

Considering this study was performed in mostly high-income countries, the researchers report hesitancy in attempting to generalize the findings to women in developing countries.

According to Dr. Regan, further studies are required to understand deeper implications of their findings. “We focused on hospitalized infection, but we should also better understand infections which may not require admission to hospital,” she added. Additionally, she suggested more research is necessary for elucidating “a better understanding of how these infections during pregnancy may impact the health of the baby.”

Testing for respiratory syncytial virus (RSV) infection during the influenza season is uncommon among pregnant mothers. 

Respiratory Syncytial Virus Testing Not Common Among Pregnant Women

Tenofovir alafenamide plus emtricitabine, which belongs in the class of nucleoside reverse transcriptase inhibitors, poses little risk for bone or renal toxicity in virologically suppressed patients with HIV, and this therapy regimen can be safely used as an alternative to abacavir plus lamivudine in these patients, according to findings from a randomized, double-blind, phase 3 trial reported in a recent issue of the

“To the best of our knowledge, this randomized, double-blind, multicentre, active-controlled, non-inferiority trial is the first to provide a head-to-head comparison of regimens containing tenofovir alafenamide plus emtricitabine with those containing abacavir plus lamivudine,” stated the study investigators Alan Winston, MD, et al. “Bone and renal safety profiles of tenofovir alafenamide plus emtricitabine and abacavir plus lamivudine were similar, reinforcing the evidence for improved bone and renal safety profile of tenofovir alafenamide compared with tenofovir disoproxil fumarate.”

Investigators screened a total of 501 HIV-1-positive adults at 79 sites across North America and Europe. All participants were virologically suppressed, as identified by HIV-1 RNA <50 copies per mL, and were on a stable 3-drug regimen comprised of abacavir and lamivudine.

The investigators randomized (1:1) participants to switch to fixed-dose tablets of 10 mg or 25 mg tenofovir alafenamide plus 200 mg emtricitabine (n= 253) or to remain on 600 mg abacavir plus 300 mg lamivudine with matching placebo (n= 248). The proportion of patients with virological suppression at 48-week follow-up comprised the primary endpoint.

Tenofovir alafenamide plus emtricitabine can be safely used as an alternative to abacavir plus lamivudine in patients with HIV.

Trial Shows Non-Inferiority Between HIV Treatment Regimens

demonstrated that the pretreatment of monocyte derived macrophages (MDMs) with high concentrations of estrogen and progesterone results in the downmodulation of proinflammatory cytokine and chemokine expression as well as the downregulation of HIV-1 replication.

“[Our] data implies that the inhibitory effect of estrogen and progesterone may be mediated through the engagement of estrogen and progesterone receptors,” according to study investigator Indira Hewlett, PhD, et al. “A probable mechanism for the regulatory effect exerted by estrogen and progesterone could be due to modulation of chemokine receptors that serve as co-receptors for HIV-1 entry.”

Investigators of this study sought to determine the molecular mechanisms of HIV-1 replication downregulation and associated antiviral responses following exposure to estrogen and progesterone treatment. After leukapheresis, the researchers isolated human monocytes from peripheral blood mononuclear cells of male and female donors who were seronegative for HIV-1.

All primary MDMs were cultured for a total of 5 days and subsequently infected with HIV-1 Ba-L, isolates of HIV-1 subtype B-NSI, and HIV-1 subtype C-NSI. Infected MDMs were pretreated with 0.6 nM mifepristone or 5 μM tamoxifen and then exposed to 110 nM estrogen or 64 nM progesterone. The researchers also used varying concentrations of the 2 hormones to determine the effect of low versus high concentrations on replication/modulation.

Exposure to high levels of estrogen and progesterone may help curb proinflammatory cytokine and chemokine expression associated with HIV-1.