Danielle Mroz, MA

People who inject drugs (PWID) who are infected with hepatitis C virus can achieve sustained viral response (SVR), despite imperfect adherence, according to the results of a new trial.

Although they are at high risk of hepatitis C virus infection and transmission, PWID tend to be excluded from treatment and coverage of treatment by health insurance because of concerns over adherence to therapy. As this population is most urgently in need of treatment, a team of investigators, led by Elana Rosenthal, MD, assistant professor of medicine in the Division of Clinical Care and Research, at the Institute of Human Virology, of the University of Maryland School of Medicine, in Baltimore, Maryland, set out to evaluate adherence in this population and determine if PWID are able to achieve SVR.

For the open-label, nonrandomized observational study—the ANCHOR study (

)—Dr. Rosenthal and her team evaluated a model of care for the treatment of hepatitis C virus infection in PWID with chronic hepatitis C virus infection. All patients in the trial are treated with direct-acting antivirals (sofosbuvir/velpatasvir [SOF/VEL] for 12 weeks, dispensed monthly in 28-pill bottles) and are also offered pre-exposure prophylaxis for HIV prevention, as well as buprenorphine for treatment of opioid use disorder when clinically indicated, according to the study design.

A total of 160 patients were screened for the trial and 100 were enrolled. The majority of the patients were male (n = 76, 76%), with a median age of 57 years (interquartile range 53-62 years), black (n = 93, 93%) and about half (n = 51, 51%) were unstably housed. More than half (n = 58, 58%) reported daily injection drug use.

 further at the 2018 American Association for the Study of Liver Diseases (

) Liver Meeting, November 9-13, 2018, in San Francisco, California.

“People who have HIV and hepatitis C virus coinfection and in HIV care had already been preferentially treated early on [for their hepatitis C virus coinfection],” Dr. Rosenthal explained. “The coinfected people that we saw were not in HIV care. Some of our patients had very low CD4 counts and so we prioritized HIV treatment in those patients.”

Three of the participants in the trial were infected with HIV and all 3 were not on treatment for HIV when they started treatment for their hepatitis C virus coinfection. According to Dr. Rosenthal, those patients were linked with care for their HIV infection. Two of the patients initiated treatment for HIV, and although 1 did not, his CD4 count was >500c/mL.

After 24 weeks of treatment, Dr. Rosenthal and her team found that even with imperfect adherence to treatment, the majority of the participants in the study were able to achieve SVR, and the majority had completed all 3 bottles of the treatment (n = 87, 87%). Twenty-one patients had completed the treatment on time (at week 12) and 46 patients completed treatment after week 12.

The team found that having a suppressed viral load (<200 IU/mL) at week 4, was significantly associated with achieving SVR, and about 84 patients achieved this goal. Interestingly, an interruption in treatment did not impact their SVR. Furthermore, although completing the full course of treatment (3 bottles) was associated with SVR (n = 87), so was completing 2 or more bottles (n = 7). Those participants who completed less than 2 bottles did not achieve SVR (n = 6).

Thirteen participants had an interruption in treatment at varying time points in the study period, and these ranged from 3 days to 70 days.

“The most surprising result we had was the number of patients who cured, despite significant nonadherence,” Dr. Rosenthal said. “I had 1 patient who completed his medication 5 weeks after week 12, and he still cured. I had a patient who disappeared for 8 weeks and then came back to treatment. He cured. I had a patient with a 70-day interruption. He cured.”

“Our per-protocol SVR was 89%, and I think that is probably more reflective of the SVR in reality because when I look at the patients who are lost-to-follow-up, 7 had undetectable viral load at week 4, 2 had unknown viral load at week 4, and 1 had a detectable viral load at week 4. This leads me to believe that the majority of people who were lost to follow-up were also cured,” Dr. Rosenthal continued.

® asked Dr. Rosenthal if the participants’ age had an impact on the results.

“I don’t think patients’ ages impacted the results because we did not really find different outcomes between the men and the women in the study,” she explained. “We were treating patients in Washington, DC, and so [in this region] there are different subgroups of the opioid epidemic. The opioid epidemic that we are seeing now in more rural and suburban areas tends to be a white, younger population. A lot of the patients we are treating [in DC] tend to be from the ‘original’ opioid epidemic that started in the 1970s and 1980s and that tends to be made up of individuals from more urban areas who are ethnic minorities. The people we are seeing are people who have been using heroin for 20, 30, and 40 years already.”

According to Dr. Rosenthal, the biggest takeaway from this study is that PWID should not be excluded from treatment for their hepatitis C virus infection because of concerns regarding treatment adherence. She explained that their findings indicate that there is not a clear factor at the beginning of treatment that should result in a patient being excluded from access to hepatitis C virus infection treatment purely because they are a person who injects drugs.

“The individuals that we were treating in this study were facing so many challenging socioeconomic and demographic factors that, if they can be cured, anyone can be cured,” Dr. Rosenthal said. “I think the biggest distinction [among this population] is going to be, interest. If patients are not interested in getting treated, it is unlikely that they are going to take the treatment. However, in anyone who is coming to you and wants to get treated for hepatitis C virus infection, I don’t think having opioid use disorder or ongoing injection drug use should preclude them from being treated and achieving cure. If patients are interested in taking treatment, they can take treatment.”

Data on any reinfections in the population treated are forthcoming; however, Dr. Rosenthal explained that if the team ends up seeing reinfections in this population, that indicates they are treating the right population.

“Our goal was to find the people who are actively transmitting [hepatitis C virus]. When you see reinfection, it means you are treating a patient population who continues to transmit the virus,” she explained. “That was critical for us: We were not just treating people with hepatitis C virus infection, but we were curing their infection to interrupt transmission to others, and helping to eliminate the epidemic.”

Dr. Rosenthal and her colleagues explained that an important component of treating hepatitis C virus infection in PWID and have opioid use disorder is understanding why they have hepatitis C virus infection, and that is their opioid use disorder. Therefore, it is important to address this underlying cause of infection during treatment for their hepatitis C virus infection to improve their overall outcomes.  

This article was previously published as, “

PWID Infected With Hepatitis C Virus Can Achieve SVR Despite Imperfect Adherence to Treatment

Articles

People who inject drugs who are infected with hepatitis C virus can achieve sustained viral response, despite imperfect adherence, according to the results of a new trial.

SVR Possible in PWID Infected With Hepatitis C Virus Despite Imperfect Adherence to Treatment

A fixed-dose combination therapy of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX, Vosevi, Gilead) was highly effective after 12 weeks in retreating direct-acting antiviral-experienced patients with hepatitis C virus infection, with and without 

, including those with prior noncompletion of treatment or poor adherence, according to results of a new study presented at the 2018 American Association for the Study of Liver Diseases (

Hepatitis C virus infection can be successfully treated with the use of direct-acting antiviral agents. In rare cases, patients can relapse; however, they can still be retreated successfully. SOF/VEL/VOX is one such treatment for hepatitis C virus infection that has shown success in patients who are treatment-experienced; however, many studies have not assessed the success of retreatment in patients with HIV or hepatitis B virus co-infection.

“I think many people expect that the drugs will work the same in HIV-positive patients as in HIV negative patients because of the early data in ledipasvir/sofosbuvir (Harvoni, Gilead) especially showing similar efficacy like in the 

,” study lead investigator Eleanor MP Wilson, MD, MHS, assistant professor of medicine at the University of Maryland School of Medicine in Baltimore, Maryland, explained in an email with 

®. “[However,] some recent data has shown that in real-world studies, patients with HIV may be less likely to succeed, because of drug interactions, immunologic effects, or other factors. [Therefore,] the newer retreatment regimens need to be tested in people with HIV infection, to show that there are no drug interactions and that patients with HIV and hepatitis C virus [or hepatitis B virus] co-infection will have retreatment options.”

As such, a team of investigators led by Wilson, pulled data from the RESOLVE trial (

), an open-label phase 2b study on the safety and efficacy of 12 weeks of a fixed dose of SOF/VEL/VOX (sofosbuvir 400mg/velpatasvir 100mg/voxilaprevir 100mg) in hepatitis C virus-infected patients with early and advanced liver disease, including those with HIV or hepatitis B virus infection, who failed previous combination direct-acting antiviral therapy. The primary endpoint is the proportion of patients who achieve sustained viral response at 12 weeks, as well as the incidence of grade 3 or grade 4 adverse events during treatment or within 30 days of treatment completion.

A total of 77 subjects were enrolled in the study at 3 sites in Baltimore and Washington, DC. The subjects were predominantly male (n = 64, 83%) and black (n = 66, 86%), with a mean age of 60 years (SD 8 years). Three-quarters of the patients (n = 58, 75%) were infected with hepatitis C virus genotype 1a, 17 patients (22%) were HIV-positive, and 2 (3%) were co-infected with HIV and hepatitis B virus.

A little over half of the participants (n = 39, 51%) had previously used intravenous drugs. About 40% (n = 31) had compensated cirrhosis at baseline and 35% (n = 27) had F2 or lower liver fibrosis.

Direct-acting antiviral experience included ledipasvir/sofosbuvir (n = 69, 89%); paritaprevir/ritonavir/ombitasvir plus dasabuvir (n = 3, 4%); elbasvir/grazoprevir (n = 2, 3%); simeprevir/sofosbuvir (n = 2, 3%); sofosbuvir/daclatasvir (n = 1, 1%), while 9 patients (12%) had received other regimens (not listed in the study abstract). A total of 19 patients (25%) had received more than 1 treatment for hepatitis C virus infection, which included 13 patients (17%) who had prior interferon experience and 11 patients (14%) who had experience with more than 1 direct-acting antiviral regimen.

A total of 22 patients (29%) did not complete their previous direct-acting antiviral treatment for reasons that included poor adherence (n = 14, 64%), interruption (n = 4, 18%), lost or stolen medication (n = 2, 9%), or adverse event (n = 1, 5%), according to the study.

Sustained viral response at 12 weeks was achieved by 70 of the 77 patients (90.9%). Of the 22 patients who did not complete their previous treatment with direct-acting antivirals, 18 achieved sustained viral response at 12 weeks. 2 were awaiting sustained viral response determination and 2 had discontinued treatment early because of intercurrent illness, according to the study authors.

A total of 3 participants (4%) discontinued treatment early for non-SOF/VEL/VOX-related adverse events. These were traumatic subdural hematoma, hypertensive urgency, and colitis. Two patients (3%) were lost to follow up, and 1 patient died because of an unrelated newly diagnosed hepatocellular carcinoma. Furthermore, 1 patient had virologic relapse.

Adverse events that were related to SOF/VEL/VOX were reported by 

5% of the participants and included fatigue, headache, diarrhea, abdominal pain, and constipation. Three grade 4 adverse events were reported, but they were determined to be unrelated to the study drug. These included subdural hematoma and new carcinoma diagnoses (squamous cell and hepatocellular).

“Our study shows that SOF/VEL/VOX is a good option, in terms of both safety and efficacy, for retreatment of hepatitis C virus infection in patients with HIV, those with hepatitis B virus infection on treatment, and in those patients who had previously not completed their initial direct-acting antiviral regimen (with either poor adherence or treatment interruption),” Wilson said. “We were able to show high retreatment responses for these traditionally difficult to treat groups, at rates similar to those reported in the registrational studies. It’s important that these traditionally understudied groups have validation that they have options for retreatment, including options that minimize drug interactions and very safe toxicity profiles.”

Looking to the future and next steps, Wilson stated that “we need to continue to show the real-world effectiveness of retreatment [for hepatitis C virus infection] to help further ongoing public health eradication efforts [of the disease].”

This article was originally published as “

SOF/VEL/VOX Successful for Hepatitis C Virus Retreatment in Patients With and Without HIV

A fixed-dose combination therapy (Vosevi, Gilead) was highly effective after 12 weeks in retreating direct-acting antiviral-experienced patients with hepatitis C virus infection, with and without HIV co-infection, including those with prior noncompletion of treatment or poor adherence.

Hepatitis C Virus Retreatment Successful with SOF/VEL/VOX in Patients With and Without HIV 

Improved indication documentation and antimicrobial stewardship involvement may improve patient outcomes in some patients who are on outpatient parenteral antimicrobial therapy (OPAT) for ease of administration (EOA) that are readmitted to the hospital, according to 

 presented by Rachel S. Britt, PharmD, Beth Israel Deaconess Medical Center, Boston, Massachusetts, at 

 held this year in San Francisco, California.

Patients who require longer-term courses of antimicrobials, such as individuals with osteomyelitis or endocarditis, may be ideal candidates for OPAT, which allows for the administration of longer courses of intravenous (IV) medications in an outpatient clinic or the patient’s home, without requiring a hospital stay. To allow for EOA, oftentimes the patient’s therapy regimen includes a switch to a broader spectrum antibiotic such as ertapenem or daptomycin that requires less frequent dosing, which is easier to manage outside of the hospital.

If a patient requires readmission, however, it may be beneficial for them to be tailored to a pre-OPAT regimen of a narrow-spectrum antibiotic to minimize any “collateral damage,” such as the development of antimicrobial resistance and 

 infections, and reduce cost, according to Dr. Britt.

“With OPAT, it’s unknown what happens with these patients after they are enrolled upon discharge,” explained Dr. Britt. “[They may be] put on one of these broad-spectrum therapies for EOA; but, if they come back into the hospital, where we have the resources to put them on narrower, less-expensive therapies that require more frequent dosing, we wanted to know, are they being put back on those agents.”

Dr. Britt stressed that there are some caveats to this, of course, as some readmissions are preplanned by medicine and surgery, and patients are only in the hospital for 1 or 2 days. Therefore, clinicians have to work closely with their inpatient and OPAT stewardship teams to identify for which patients the switch would make sense.

For their single-center, retrospective study, Dr. Britt and her team reviewed the charts of adult patients who had been enrolled in OPAT and discharged from the hospital between January 1, 2014, and September 30, 2017, on either daptomycin or ertapenem for EOA. Those patients who had been receiving directed carbapenem or daptomycin before being enrolled in OPAT were excluded from the study.

The primary outcome was the percentage of patients who were readmitted to the hospital during or within 90 days of the OPAT course of therapy and maintained on an EOA regimen. Inpatient therapy cost, rates of 

, and adverse drug reactions were secondary outcomes (see video).

EOA regimens were continued in 27% of the readmissions. The results indicated that 71 of the 188 patients identified as receiving an OPAT EOA regimen were readmitted to the hospital (n = 113 unique readmissions). Eighty-one percent of the patients were male, and the median age was 57 years. About 8.6% of the patients on daptomycin ended up with 

 versus 6.1% in the ertapenem arm (see video). According to the study abstract, the median drug acquisition cost of inpatient EOA was $112 per readmission.

According to Dr. Britt, these results indicate that with better coordination between the OPAT and antimicrobial stewardship teams, patients may be given more appropriate antimicrobial regimens to improve patient outcomes and reduce costs (see video).

Better provider order entry indication documentation and coordination between OPAT and stewardship teams may facilitate appropriate regimen tailoring in certain patients upon hospital readmission during OPAT.

Since the completion of the study, Dr. Britt and her team have presented these results to their OPAT team and they look forward to discussing and determining any changes that need to be made to create the best regimens for these patients, which may include remaining on the broad-spectrum therapy (see video).

Some limitations of the study include that it was a retrospective, observational, single-center study and that data collection was limited to the documentation bias and information that was contained within the medical records. Furthermore, as this was a single-center study, the investigators were unable to see whether or not patients had been admitted to another medical center in between discharge and readmission, and if they were continued on their OPAT therapy.

Session: Poster Abstract Session: Clinical Practice Issues: HIV, Sepsis, QI, Diagnosis

Poster 1923: OPAT or no-PAT? Evaluation of Outpatient Parenteral Antimicrobial Therapy (OPAT) Patients Receiving Daptomycin or Ertapenem for “Ease of Administration”

C. McCoy, Merck Inc: Scientific Advisor , Consulting fee . Allergan: Scientific Advisor , Consulting fee .

M. V. Mahoney, Melinta Therapeutics: Consultant , Consulting fee . Cutis Pharma: Consultant , Consulting fee . Tetraphase Pharmaceuticals, Inc.: Consultant , Consulting fee . Roche Diagnostics USA: Consultant , Consulting fee .

Efforts such as improved indication documentation and antimicrobial stewardship involvement may improve patient outcomes in some patients who are on outpatient parenteral antimicrobial therapy (OPAT) for ease of administration (EOA) that are readmitted to the hospital.

OPAT-Antimicrobial Stewardship Team Coordination Ideal For Improving Patient Outcomes Upon Readmission

New software to facilitate prior authorization helped streamline the approval process and increase antimicrobial use tracking at the Hospital of the University of Pennsylvania (HUP), according to the results of a new 

Many antimicrobial agents require prior authorization before use, and indeed, prior authorization is a 

core antimicrobial stewardship intervention

 recommendation by the US Centers for Disease Control and Prevention. At HUP, prior authorization has been a cornerstone of their antimicrobial stewardship program since its inception; however, the process was not always smooth.

“There were several steps to our original prior authorization process,” explained investigator, Keith W. Hamilton, MD, assistant professor of Clinical Medicine, University of Pennsylvania School of Medicine, HUP, Philadelphia, Pennsylvania. “Providers were required to call a pager. They would send a numeric page through to the pager and 1 of our pharmacists or 1 of our infectious disease physicians would return the page. If the infectious disease physician or pharmacist approved the drug, they would actually have to call in to the pharmacy to let them know that they granted their approval.”

In addition to being a rather inefficient, multistep process, use of the pager system to request approval sometimes meant that pages were missed, particularly if providers sent pages during the hours that the pager was not operational. “During that time, pages would just go into the ether and no one would be able to get the request,” lamented Dr. Hamilton. Furthermore, the antimicrobial stewardship team found that it was rather difficult to audit the process.

It was for these reasons that Dr. Hamilton and his team set out to study the effect of implementing a new electronic prior authorization approval platform that worked within their existing clinical decision support platform.

The new software was introduced to prescribers at HUP in January 2017. The study was a descriptive analysis of the process over the entire year of 2017. Specifically, Dr. Hamilton and his team wanted to look at the time it took for approvals to be submitted in the system, as well as the indications and antibiotics for which approvals were requested.

In the new system, when a provider enters in an order for a restricted agent, the name of an approver is now a required field. The request for approval is triggered when the provider selects the patient and indication for use. Providers have the option to select any additional risk factors they may want to alert to the attention of the approver, as well as any relevant cultures. The desired antimicrobial is selected, and then the provider enters in their contact information and submits the request. The antimicrobial stewardship team is able to respond to the request through the system, and following the approval and pharmacy safety check, the drug is approved, oftentimes without having to make a phone call.

In addition, to streamlining the approval process, Dr. Hamilton explained that the new software also aided in tracking antibiotic use.

“Previously, before the new system, we had to have a manual spreadsheet entry system for tracking what antibiotics were approved over time,” said Dr. Hamilton. “It was difficult to track, and it required additional entry steps.”

He explained how the new software increased the efficiency of tracking antibiotic use and approvals, as well as additional capabilities it afforded that would have been too laborious to complete previously (see video).

With the new system, Dr. Hamilton and his antimicrobial stewardship team were able to respond to requests for prior authorization quickly, with a median time to response of 18 minutes (range 8-42 minutes) during antimicrobial stewardship program hours, as well as track antibiotic use more efficiently. In addition, the antimicrobial stewardship team has not had to report any safety events for missed pages, and has been able to more efficiently audit antibiotic prescribing and they readily see on their screens more clinical information about the request than they were receiving in the past, thus making them feel more informed on the process.

Study results indicated there were a total of 437 unique users of the new system. A total of 1934 patients had 3329 requests submitted. Indications for prophylaxis, other, and pneumonia, were the most frequent, and the most commonly requested antibiotics were levofloxacin (36.76% of patients), followed by meropenem, caspofungin, and fluconazole. A total of 88.7% of the overall requests by providers were approved.

The new system was quickly adopted by providers at HUP and in fact, the providers using the system have been extremely pleased with it as they aren’t required to wait by the phone for a call back with the approval (see video).

Implementing a new software system was not without its challenges, according to Dr. Hamilton. The introduction of a new workflow requires a lot of buy-in from all individuals who are involved in the process, and as such, he stressed the importance of meeting with all key stakeholders in the process to understand, before implementation, their perspectives and needs on the process. Dr. Hamilton and his team revised the software iteratively, based on these needs and requests.

Educating an entire institution on the changes with new software also proved challenging, and so Dr. Hamilton and his team provided a host of upfront education during the first 2 months of the software rollout aimed at all clinicians who would interact with the software, from house staff, to advanced practice providers, to physicians’ assistants.

Furthermore, it was important that the new software worked within the provider’s current clinical decision support software, according to Dr. Hamilton (see video).  

For providers looking to implement a similar program at their institution, Dr. Hamilton offered the following advice (see video).

Limitations of the study include that is was a single-center study, conducted at a large academic hospital with a moderately restricted formulary. According to Dr. Hamilton, about 60% of all of antimicrobials have some sort of a restriction attached to them, making their hospital pretty heavy on prior authorization. Furthermore, the stewardship program at HUP has been in effect for over 25 years, and so the results of the study may not be applicable to other institutions.

Session: Poster Abstract Session: Antimicrobial Stewardship: Interventions Leveraging the Electronic Health Record

Poster 184: Implementation and Evaluation of an Electronic Antimicrobial Prior Authorization Approval Process at a Large Academic Medical Center.

J. Mehta, ILUM Health Solutions: Consultant , Salary .

J. Olson, ILUM Health Solutions: Consultant , Salary .

W. J. Ketcherside, ILUM Health Solutions: Consultant , Salary .

L. Hunt, ILUM Health Solutions: Consultant , Salary .

B. Palermo, ILUM Health Solutions: Employee , Salary .

New software to facilitate prior authorization helped streamline the approval process and increase antimicrobial use tracking at the Hospital of the University of Pennsylvania.

Antimicrobial Stewardship Processes Streamlined with Software

The next-generation fixed-dose combination therapy of glecaprevir/pibrentasvir (Mavyret (G/P)) was 

 by the US Food and Drug Administration (FDA) in August 2017 for the treatment of chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. The combo was also approved for adult patients with HCV genotype 1 infection who had been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both.

This week, the FDA approved revisions to the drug’s 

 to include dosing recommendations for individuals who have undergone liver or kidney transplants, those who are treatment-naïve or PRS treatment-experienced adults with HCV/HIV-1 coinfection without cirrhosis or with compensated cirrhosis, as well as treatment-naïve or PRS treatment-experienced adults with liver or kidney transplant without cirrhosis. (

 with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor.)

This update to the drug’s label was based on safety and efficacy data gleaned from the HCV/HIV-1 coinfection study (M14-730) and the live and renal transplant study (M13-596).

Research has shown that G/P has demonstrated high sustained virologic response (SVR) in patients regardless of HCV genotype or baseline patient or viral characteristics; however, about 1% of patients treated in the G/P clinical trial program to-date have had virologic failure (VF). Those patients were enrolled in the MAGELLAN-3 (

) retreatment study, which is “an ongoing phase 3b, open-label trial, in which patients who had VF following G/P are retreated with the combination of G/P 300 mg/120 mg once daily (QD) + sofosbuvir (SOF) 400 mg QD + ribavirin (RBV) 1000—1200 mg (weight based, twice daily).”

The outcomes of this research at weeks 4 and 12 post-treatment were presented at the 

25th Conference on Retroviruses and Opportunistic Infections

A total of 24 participants (19 male; 5 female) were distributed into 2 arms, A and B. Those patients (3) who “were non-GT3- infected, non-cirrhotic, and naïve to protease inhibitor and/or NS5A inhibitor prior to VF with the G/P regimen [were placed into Arm A],” according to the investigators. These patients received 12-weeks of treatment with the study combination regimen. Arm B participants—all other patients (21) who did not meet the criteria for Arm A&mdash;received the combination regimen for 16 weeks.

Further patient characteristics for Arm A include:

NS3 alone (None); NS5A alone (1 participant); NS3 + NS5A (1); missing (1)

HCV GT1 (7 participants); HCV GT2 (None); HCT GT3 (14)

NS3 alone (None); NS5A alone (11 participants); NS3 + NS5A (6); Missing (4)

The primary outcome of the trial is SVR at post-treatment (PT) Week 12 [SVR12]. Baseline resistance and safety were also assessed. All patients continued with the trial to 12 weeks and “no significant laboratory abnormalities were observed,” according to the study authors.

Dr. Wyles discussed the results of the trial at 4 and 12 weeks post-treatment (see 

The retreatment regimen was found to be well-tolerated, with about 10% of the study participants reporting adverse events (AEs). Chief among these were headache (25.0%) and pruritus (25.0%), followed by dizziness (16.7%) and irritability (16.7%). One participant had a serious AE (cholelithiasis); however, the study investigators deemed this to be unrelated to the treatment regimen.

Based on the results of the study, Dr. Wyles had the following to share moving forward (see 

The combination of direct-acting antiviral agents glecaprevir/pibrentasvir (G/P), sofosbuvir, and ribavirin is now approved for new patient populations.
 

Direct-Acting Antiviral Combo Yields High Rates of SVR in Patients with Previous Virologic Failure

, indicate that after 48 months, fewer cases of cervical intraepithelial neoplasia (CIN) grade 2 or 3 or worse (CIN2+, CIN3+) were found in women who were screened for cervical cancer with primary cervical human papillomavirus (HPV) testing versus women who were screened with cytology alone. These results suggest that HPV testing is able to detect CIN earlier and more accurately than cytology.

cervical cancer is one of the most preventable cancers

 in the United States through early detection and treatment of abnormal cervical cell growth prior to cancer development, about 12,000 women are diagnosed with cervical cancer in the United States each year. Two traditional screening tests—the Pap (cytology-based) and HPV tests&mdash;are used to detect cervical cell changes as well as HPV. Research has shown that about “

 are associated with a persistent cervical infection with an oncogenic HPV genotype preceding the invasive tumor.”

To this end, a team of investigators, led by Gina Suzanne Ogilvie, MD, DrPH, of the University of British Columbia Faculty of Medicine, in Vancouver, Canada, conducted a randomized clinical trial (HPV FOCAL) which included more than 19,000 women who were recruited between January 2008 and May 2012. Those women who fit the study criteria of being between the ages of 25 and 65 (mean age, 45 years), with no recent clinical history of CIN2+, or no history of invasive cervical cancer or hysterectomy, no recent PAP (within the past year) and who were not taking immunosuppressive therapy were included in the study.

Participants were randomized into either an intervention group (n = 9552) which received HPV testing, or a control group (n = 9457) which received liquid-based cytology (LBC) testing. Those patients in the HPV group who had negative results after the first round of testing returned for follow-up after 48 months, while patients tested with LBC who had negative results returned at 24, then 48 months.

At the end of the 48-month checkup period, both groups received HPV and LBC co-testing.

The results of the study indicated that at 48 months, patients in the intervention group had significantly fewer incidence rates for CIN3+ (2.3/1000; 95% CI; 1.5-3.5) versus patients in the control group (5.5/1000; 95% CI; 4.2-7.2), with a risk ratio of 0.42 (95% CI; 0.25-0.69).

Patients in the intervention group reported similarly significant reduced rates of CIN2+ incidence (5.0/1000; 95% CI; 3.8-6.7) versus patients in the control group (10.6/1000; 95% CI; 8.7-12.9) at 48 months. The CIN2+ risk ratio was 0.47 (95% CI; 0.34-0.67).

According to the investigators, participants who were HPV-negative at baseline had a significantly lower cumulative CIN3+ incidence at 48 months than women who were cytology-negative, with a risk ratio of 0.25 (95% CI; 0.13-0.48). 

Based on these results, the investigators concluded that primary HPV testing is able to detect cervical neoplasia earlier and more accurately than cytology.

Previous research has shown that primary HPV testing alone, or in combination with cytology is associated with increased detection of precancerous lesions in the first round of screening; however, until this study there was a dearth of research on the results beyond the initial phase.

“Previous studies found the benefit of HPV and cytology co-testing was based primarily on the contribution of HPV, which this trial now prospectively validates,” according to the study authors. “Further analyses modeling the cost-effectiveness of HPV primary screening using parameters from this study will be carried out to assess the potential economic effect of moving to HPV-based screening.”

L. Stewart Massad, MD, of the department of Obstetrics and Gynecology at the Washington University School of Medicine in St. Louis, Missouri, wrote in an accompanying 

 on the study that “substantial patient education” stands in the way of HPV testing becoming the primary screening method over cytology and Pap testing. He went on to explain that women need to be educated about the importance of these tests for sexually transmitted diseases and how left untreated, HPV can progress toward cancer. Although the prevalence of HPV continues to decrease since the introduction of a vaccine, testing is still paramount to patient health and Dr. Massad believes that the introduction of new screening tools needs to be combined with efforts to educate and screen women in order to truly make progress in the fight against cervical cancer.  

A version of this article was originally published by 

HPV Testing Improves on Cervical Neoplasia Detection Versus Cytology Testing

Study results suggest that HPV testing is able to detect cervical intraepithelial neoplasia earlier and more accurately than cytology.

Danielle Mroz, MA

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