Better options for treating resistant HIV

Better Options Available for Resistant HIV

Patients with multidrug-resistant (MDR) HIV currently make up a smaller but still challenging part of the population living with HIV. With careful monitoring and new drugs coming, providers can still help their patients.

“It’s really great that we have a rela- existing drugs, because their mechanisms tively low number of patients with this of action are different,” Appelbaum said. issue,” said Milena Murray, PharmD, “If you’re resistant to the older drugs, you BCIDP, AAHIVP, an associate professor are not automatically resistant to these.” of pharmacy practice at Midwestern University-Chicago College of Pharma- New Medication Help cy, and an HIV/ID clinical pharmacist One of the newer medications is at Northwestern Memorial Hospital, an attachment inhibitor, ibalizumabin Chicago. “Patients can have one or uiyk (Trogarzo, Theratechnologies), two mutations and still have plenty of approved by the FDA in 2018. The options at this point.” drug has a novel mechanism of action.

About 3% to 7% of the HIV population A monoclonal antibody that binds to are considered MDR and need addi- the surface of immune cells, ibalitional new agents, according to Michael zumab blocks the steps required for Kozal, MD, a professor of medicine at viral entry into cells. Multiple centhe Yale School of Medicine, in New ters participated in the pivotal study Haven, Conn., and the chief of staff at the FDA considered for approval, describing phase 3 trial results. “One of the caveats of HIV treatment the VA Connecticut Healthcare System. enrolling 40 patients with MDR HIV. Fostemsavir is a prodrug whose active is you never want to add on or substitute He has studied HIV multidrug resis- Patients received a dose of IV ibali- metabolite, temsavir, is an attachment just one drug if patients have resistance tance since 1991. zumab-uiyk in addition to their fail- inhibitor that prevents viral entry into to multiple drugs,” Appelbaum noted.

People can develop resistance to multi- ing regimen for one week. After that host immune cells by binding to a gly- “You want to have two, and ideally three, ple drugs for several reasons, experts said. period, they received ibalizumab-uiyk coprotein on the surface of the virus. In active medications.”

Children who acquire HIV perinatally with optimized treatment regimens the ongoing BRIGHTE trial in 23 coun- When monitoring patients, Murray often have problems adhering to medicaca- tries, 371 patients with MDR HIV-1 said, always check the viral load. “If tion, and can burn through several drugs ugs infection were given fostemsavir along patients are undetectable, that’s the best- by the time they reach adolescence and and with their failing HIV regimen. After case scenario,” she said. “But if we can’t young adulthood. Some patients are less ess 48 weeks of therapy, 54% of ran- get them to undetectable, we want to adherent to medication because they’re re domized and 38% of nonrandom- make sure their viral load isn’t continuin and out of the criminal justice sys- ized patients who took the drug ing to increase.” tem, have substance use issues or for r had undetectable viral RNA levother reasons, and develop viral muta- els. The most common side effects Don’t Forget CD4 Counts tions that render the drugs ineffective. e. included diarrhea, nausea and upper In addition, monitor CD4 counts Some patients also experience toxicities ties respiratory tract infections. to make sure they’re not decreasing. or cannot tolerate some of the existing ing “The data were very promising in that Check for any signs or symptoms of drug classes, or are long-term survivors ors the viral load stayed nondetectable in a opportunistic infections and make sure initially diagnosed in the late 1980s to large number of patients out to week 48,” any comorbid conditions are being early 1990s who have gone through a Kozal said. “There’s no cross-resistance addressed. Follow all guideline recommyriad of drugs over time. to other classes, so we think it’s going to mendations for screenings.

“We have had a number of great agents be helpful for people who have exhaust- T-cell count also is important, “because over six different drug classes, but some ed other drug classes or can’t take other if you don’t have the virus under control, people develop drug resistance,” Kozal drug classes because [of intolerance].” the immune system is being constantly said. “It sounds like a lot—six classes— Current management of patients still attacked by the virus, and so the patient but as patients have reactions, it lim- for six months. After one week on comes down to individual resistance pro- is at risk for opportunistic infections and its the drugs they can take, and some ibalizumab-uiyk, most patients (83%) files, Murray said. Protease inhibitors malignancies,” Appelbaum said. patients are infected with drug-resistant experienced a decrease in viral load are good options for some patients with Be mindful that as patients get oldvirus. There is a need for new agents that (N Engl J Med 2018;379[7]:645-654). drug resistance. Maraviroc can be helpful er and need to add statins or antihave different mechanisms of action.” After 25 weeks, nearly half saw their but requires a tropism assay. Enfuvirtide hypertensives to their regimens, drug

Until the past couple of years, there viral load fall below the level of detec- (Fuzeon, Genentech) is an injectable that interactions can occur with their HIV were a limited number of targets on HIV tion. The researchers also reported an may cause painful injection site reac- medications, Murray said. Then you that could be hit by available medica- increase in CD4 T cells, which are a tions and is usually used as a last resort. can run into the issue of not being able tions, said Jonathan Appelbaum, MD, marker of immunity. At times, adding an integrase inhibitor to to change the antiretroviral therapy FACP, AAHIVS, a professor and the chair “This is a great drug that has worked the regimen will be enough if there are to mitigate drug interactions because of the Department of Clinical Sciences well,” Appelbaum noted, but because it is no mutations to this class. there aren’t any other options to treat at Florida State University College of given intravenously, it’s not used early in “Sometimes we need to have patients the drug-resistant HIV. Medicine, in Tallahassee. HIV treatment. on four to five medications, but that regi- Overall, have good encouragement and

Recently, several new targets have The FDA recently approved fos- men is able to get them to an undetect- support for your patients, Kozal advised: emerged, including drugs designed to temsavir (Rukobia, ViiV Healthcare), able viral load,” Murray said, while other “You’ve got to take the drugs in order for inhibit the maturation of the virus inside which was developed specifically for times medications are not enough to get them to work.” —Karen Blum cells or prevent its entry into immune patients with MDR HIV and works by a to undetectable but can keep the viral system T cells. novel mechanism of action, said Kozal, load at a lower point. Ibalizumab can be

“The good thing about these new drugs the lead author on a recent article a good option for patients who are extenis they don’t show cross-resistance to the (N Engl J Med 2020;382[13]:1232-1243) sively drug-resistant, she added.

After one week on ibalizumab-uiyk, 83% of patients experienced a decrease in viral load.

Source: N Engl J Med 2018;379(7):645-654. ‘Sometimes we need to have patients on four to five medications, but that regimen is able to get them to an undetectable viral load.’

—Milena Murray, PharmD

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Study Sees Vast Treatment Gap for Hepatitis B

Nearly half of all eligible patients infected with chronic hepatitis B do not receive treatment for the disease, a new study has found.

The investigators said the research was bolstered by the large, ethnically diverse multicenter cohort that formed the foundation of the analysis.

“We know that hepatitis B is predominantly a disease affecting ethnic minorities, as well as underserved and vulnerable populations,” said Robert Wong, MD, MS, of the Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, in Stanford, Calif. “Many data show that hepatitis B remains underdiagnosed due to suboptimal awareness, screening, diagnosis and linkage [to care].”

Wong’s study focused on patients who had already been diagnosed with hepatitis B. “This is sort of considered the lowhanging fruit, because these are patients who have already been diagnosed, yet continue to experience delays in progressing through the cascade of care to receive antiviral treatment,” he said.

The researchers evaluated 5,157 adults with chronic hepatitis B who presented to four urban safety-net heath systems between Jan. 1, 2010, and Dec. 31, 2015, and who had at least two years of follow-up. The disease was confirmed with laboratory data. Criteria from the American Association for the Study of Liver Diseases were used to determine treatment eligibility.

“The diversity of the group was definitely a strong point, because many previous hepatitis B studies were predominantly Asian,” Wong told Specialty Pharmacy Continuum. “But we actually captured a very diverse hepatitis B population: 34.6% were African American, 35.7% non-Hispanic white and 7.7% Hispanic.”

Of the patients, 46.8% were eligible for treatment, with significantly higher rates of treatment eligibility among men than women (58.2% vs. 32.9%; P<0.001). Similar rates of eligibility were found across race and ethnicity.

In a study presented at the 2020 International Liver Congress (abstract FRI404), the investigators reported that only 55.7% of treatment-eligible patients received treatment for chronic hepatitis B. Of that group, only 17.5% received treatment within six months of becoming eligible.

Women with treatment-eligible disease were significantly less likely than men to receive therapy (41.2% vs. 62.5%; P<0.01), according to the researchers. Asians were significantly more likely to be treated than whites (49.5% vs. 39.1%; P<0.01).

“This highlights a missed opportunity and a gap in our delivery of care for hepatitis B patients,” Wong said. “We believe this identifies areas where we can develop targeted quality improvement programs to try to address these shortcomings.”

Such efforts include improved linkage to care in at-risk populations, increased patient and provider awareness regarding treatment guidelines, and general hepatitis B educational efforts targeted at patients, he said.

Poor adherence to treatment can be ‘I think these low numbers really scream that we need to invest more resources in addressing the low rates of hepatitis B treatment in safety-net and vulnerable populations.’

—Robert Wong, MD, MS

another barrier to comprehensive care. “That’s where taking a comprehensive approach can help—one that targets providers, disease and health systems, and also invests in patient-centered education and engagement,” Wong said. “We used this approach in previous work and found it actually led to better follow-up and improved treatment rates.”

Future efforts, according to Wong, likely will include prospective quality improvement studies. “Now that we’ve identified the problem, we want to evaluate how we can improve this going forward,” he said. “So, we and others are planning prospective studies to see how we can better identify, engage and improve treatment rates for these hepatitis B patients. I think these low numbers really scream that we need to invest more resources in addressing the low rates of hepatitis B treatment in safety-net and vulnerable populations.”

Sammy Saab, MD, MPH, a professor of medicine and surgery at the David Geffen School of Medicine at the University of California, Los Angeles, said the results are a call to action to identify barriers to therapy and develop protocols that extend treatment to a broader range of patients with chronic hepatitis B.

“We need to improve education. People need to understand that hepatitis B is a carcinogen, and a major reason for cirrhosis and liver cancer,” Saab said. “We also need to educate them that we have great therapies that are safe, effective and tolerable. We need more studies to find out where these barriers exist, whether it be at the patient level, office level, pharmacy level, insurance level or physician level.” —Michael Vlessides

The study was supported by a grant from Gilead Sciences. Saab reported a fi nancial relationship with Gilead Sciences.

Opioid Crisis Also Affects HAV and HBV Rates

Thanks to direct-acting antivirals, hepatitis C virus (HCV) has gotten a lot of attention, but infectious disease experts are starting to hear more about hepatitis A and B viruses because cases are increasing due to the opioid crisis.

For the last 15 years, hepatitis A virus (HAV) had been associated mostly with international travel to countries where the virus is endemic, and with contaminated food, but current U.S. outbreaks of HAV are now primarily spread by person-to-person contact.

“We’re seeing really large person-toperson outbreaks of hepatitis A among persons who report drug use and homelessness,” said Monique Foster, MD, MPH, a medical epidemiologist in the CDC’s Division of Viral Hepatitis. She said 30 states have reported HAV outbreaks, 34,297 cases had occurred by September, with more than 21,067 hospitalizations and 333 deaths.

The spike in infections can be attributed to factors associated with homelessness and drug use, as well as low vaccination rates among groups at risk for infection, according to Foster. “Since hepatitis is spread by fecal–oral transmission, access to clean, sanitary facilities is really important, along with vaccination of populations at highest risk,” she said.

“Public health authorities have been trying to address the outbreak with temporary facilities” that include restrooms with handwashing facilities, as well as mobile vans that bring vaccines to those at risk, said Ravi Jhaveri, MD, a professor of pediatrics at Northwestern University Feinberg School of Medicine, in Chicago.

People with HBV and/or HCV are at higher risk for adverse outcomes when infected with HAV—notably liver failure, and possibly death, according to Foster.

The Advisory Committee on Immunization Practices (ACIP) of the CDC recommends certain at-risk populations of adults be vaccinated against HAV, including: • people experiencing homelessness; • people who use drugs; • men who have sex with men; • travelers to countries with medium to high rates of endemic HAV; • people in close personal contact with an international adoptee in the first 60 days after arrival from a country with endemic HAV; • people who work with HAV in laboratories or with infected nonhuman primates; and • people with chronic liver disease or clotting factor disorders.

Additionally, incarcerated people and, in some cases, those who work in close contact with them are also at high risk. People who have sex with someone with HAV should be vaccinated “within the 14-day window of being exposed,” Foster said.

Vaccine coverage for at-risk adults is wanting. According to the 2017 National Health Interview Survey, 10.9% of adults aged 19 years or older