“I’m always amazed by how modern medicine is advancing in treating HIV. And I’m very fortunate to live in an era in which I can be a person living with HIV long-term and still be able to live a long and healthy life.”
—Josué E. Hernández
HIV treatment has certainly evolved since the early days of the epidemic. In the 1980s and ’90s people living with HIV/AIDS (PLWHA) were taking multiple pills, two or three or even four times a day. These regimens came with complicated food restrictions and horrible side effects. Excruciating peripheral neuropathy. Dangerously elevated triglyceride levels. Uncontrollable diarrhea. Vomiting. Lipodystrophy that caused facial wasting and belly protrusions and “buffalo humps”—all of which took their toll physically and emotionally.
Once protease inhibitors (PIs) were approved in the mid- to late ’90s, and Norvir (ritonavir) was approved as a PI booster at only 100 milligrams per day, many PLWHAs were able to scale down their regimens to five pills per day. Many of the terrible side effects diminished or went away completely. In 2006, the FDA approved the first one-pill, once-a-day medication, Atripla. And Truvada—a combination of two medications (tenofovir DF and emtricitabine) in one that for years was used as the backbone in most regimens to treat HIV—was approved in 2012 for PrEP.
We’ve come a long way since the toxic monotherapy of AZT, and HIV treatment is much easier than it used to be, but… what if it could be even easier and there were more treatment options? Get ready, because monthly injections and implants are on the way—along with some intriguing new prevention methods. All thanks to technology that almost seems like science fiction.
In 2019, there are currently 13 single-tablet regimens (STRs) in the U.S. market, of which six contain an integrase inhibitor. Each contains two to four HIV medications (the fourth being a booster such as ritonavir or cobicistat). STRs are much easier than taking 10 or 20 or even five pills daily. But many PLWHA (especially those who were diagnosed in the 1980s and ’90s) experience “pill fatigue.” Plain and simple, they are sick and tired of taking pills every day year after year and being told they would have to take them every day for the rest of their lives. Also, newly diagnosed and otherwise healthy PLWHAs have to adjust to the new routine of taking a daily medication, which can be a huge challenge. But a possible solution may be coming.
It‘s expected that the U.S. Food and Drug Administration (FDA) will approve the first long-acting injectable form of HIV combination therapy before the end of 2019. “The first two drugs that are coming are injectable long-acting cabotegravir (an integrase inhibitor) and injectable long-acting rilpivirine (a non-nucleoside reverse transcriptase inhibitor),” said Dr. Judith S. Currier, UCLA Center for Clinical AIDS Research and Education (CARE). “I think this is a big deal and an important milestone in HIV therapy.”
Once approved by the FDA, the drug will be given orally for a short time to make sure patients can tolerate the medication and that there are no serious side effects. If all goes well, patients would be switched to monthly injectable therapy. Shots would be given in the butt (a shot in each cheek); patients would have to go to their doctor’s office or clinic to receive the injections (no self injections at home). Patients (hopefully with help from their clinic or ASO) would have to remember—and be willing and able—to go to their medical provider monthly, which could be difficult for some, especially people living in rural areas or those who have competing priorities, like childcare, eldercare, complicated work schedules, mental health issues, or other physical problems.
“It is very exciting to have injectable treatment options so close to being available in the clinic,” said Dr. Currier. “I suspect that the initial approval will be for people who are already suppressed and possibly for people who are starting treatment. There are many people who are suppressed who don’t like taking pills for whom this will be a great option, but it will likely require visits to the clinic every month, for people who currently only come in twice a year. It is critical that we learn how to use long-acting injectable treatment for those who have not been suppressed. I have heard from many PLWHAs who have not been able to remain suppressed, that the daily pill-taking ritual is a psychological barrier to adherence—a daily reminder of HIV. If we can demonstrate that long-acting injectable treatment will overcome this barrier, it will be a major advance.
“Also, long-acting treatment with cabotegravir plus rilpivirine is currently being studied in ACTG 5359, the LATITUDE study,” Currier added. “This study is designed for people who have not been successful in staying virally suppressed. ACTG sites around the United States are actively recruiting for this trial now. More information about the LATITUDE trial can be found at actgnetwork.org/study/a5359-latitude-study. Currently, two injectable drugs are given monthly, but there is some emerging evidence that they may be able to be given every two months. Ultimately we hope that we can develop agents that will last even longer.”
A few people from southern California living with HIV were asked for this article if they would switch to this new kind of treatment. Here’s what they had to say:
“The news about the first HIV injectable medication sounds exciting—and, even convenient,” said Josué E. Hernández. “But, my experience has been negative in trying new HIV medications when they first come out on the market. Some of the negative side effects I’ve had include getting a rash all over my body with one medication and getting blisters on my hands with another medication. As a result, I think I would rather wait and see how the general population reacts to the new HIV injectable medication before I consider giving it a try.”
In a follow-up question that included information about the oral lead-in period, Hernández added, “I would be open to trying the pill form first to test for side effects. But I am not thrilled about going to my doctor or a pharmacy to get the injection. Because I’ve been on treatment and undetectable for nearly 11 years, I only see my doctor every six months. And I get my medication sent in the mail. Ideally, I would prefer to administer the injectable myself, like people who are living with diabetes.”
“As someone living with HIV, I would not be willing to change my current daily pill regimen for this new process,” said Dontá Morrison. “Reason being is that [my body] has become accustomed to what I am on, and I do not want to risk shifting any of the positive strides I have made. Also, the thought of an injection is too extreme. What if something goes wrong? Unlike traditional medications, it won’t flush out of the system as easily. For me, it feels too invasive. But I have also been living with the virus since 1999, and my thoughts on treatment may be a bit antiquated.” Asked about an oral lead-in to the injectable, Morrison added, “That would make a huge difference. Yes… I’d be more willing to try.”
“After nearly a decade of taking Atripla, I chose to transition to a two-pill, once-a-day regimen,” said Carlos Cuauhtémoc Aguas-Pinzón. “As a treatment educator, I did some research and asked a few providers, including my own, to find the best fit for me. I’ve been on my current regimen—DTG, FTC/TAF [Tivicay plus Descovy]—for 18 months and am extremely pleased with how it’s working. The pills are conveniently small and I can fit a couple doses in a discreet pill keychain. However, I’ve sometimes reached for my meds and realize I only have one of the two pills. As far as an injectable, I’ve been waiting for it since it was mentioned at a conference several years ago. I kept my eye out for the trials but was not able to find one to enroll in. Now that it’ll be available soon, I am very interested to talk to my provider about switching regimens. It’s going to depend on co-pay, convenience, side effects, and frequency. I spoke with a couple of my treatment education clients about it, and both were enthusiastic about the possibility. We all concluded that 12 injections are better than 365 pills a year (730 pills for me; they’re on single-tablet regimens). I really hope that HIV medical clinics take note of the rates of viral suppression among their patients, especially those with inconsistent treatment adherence.”
“I’ve had HIV since 1995, and I’m so damn tired and have been so damn tired of taking these damn pills. I’d try the shots!” said Sylvia Jones. “To hear about this—it’s exciting for me.”
‘Implant technology is continuing to advance, and this may be another option for the delivery of long-acting ART.’
Researchers are also working on HIV treatment implants. These devices would be about the size of a matchstick that would slowly and consistently release HIV medication, but then be replaced after treatment has run out. Medication implants are currently used in at least two ways: as birth control (Nexplanon) for women, implanted in the upper arm, and as testosterone (hormone replacement therapy) for both men and women, implanted in the butt cheek. Again, these implants are removed and replaced when the medication has been completely dispensed, or if the patient wants it removed. Both insertion and removal need to be done in a clinic or doctor’s office by a medical professional, and require a small incision. Researchers are also studying implants that would completely dissolve in the body once all the medication has been dispensed.
Looking ahead to an implant, it would contain a complete treatment regimen so patients would not have to take any pills. “Implant technology is continuing to advance, and this may be another option for the delivery of long-acting ART,” said Dr. Currier. “As these studies are less further along, we hope to see more clinical studies of these agents coming soon. The benefit here would be that the implant could be removed if there was an adverse event, or if a change in treatment was needed.”
MK-8591, an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI, a potential new HIV drug class) being developed by Merck, is one of the experimental drugs being studied as a possible implant. Data from a small Phase II study (in combination with other HIV medications) were presented in July at the International AIDS Society (IAS) Conference on HIV Science in Mexico City. Researchers reported that after 24 weeks, all study participants remained undetectable; research is ongoing.
We really don’t know how long these implants will last in the body. PLWHA could potentially go two years without needing to remove or replace treatment implants. How amazing! But the entire care team—PLWHA, doctors, case managers, and others—would have to prepare to face a new set of potential adherence challenges. What if someone moves or becomes incarcerated? Or relapses? Or becomes homeless? HIV professionals will have to stay in close, continuous contact, and be ready, willing, and able to track them down before the implant expires. Implants can only last so long, and everyone—including the patient—will have to plan ahead.
Women and HIV prevention
Thanks to Truvada for PrEP, there’s been a decline in HIV infections, particularly among white MSMs. Women, however, are taking PrEP at much lower rates than men. This is because of a variety of reasons: insufficient prevention education, reduced access, and less outreach to women vulnerable to HIV infection. amfAR reports that, in 2018, women accounted for 52% of all adults worldwide living with HIV. A women-centered HIV prevention modality is urgently needed. Enter vaginal rings.
NuvaRing is an FDA-approved method of birth control that is inserted into the vagina and replaced every 30 days. The patient can insert and replace the ring herself. NuvaRing releases two different hormones that prevent pregnancy, and gives women tremendous power to control their reproductive rights without the knowledge of their sexual partners. What if we take what we know about NuvaRing and use something akin to it to prevent HIV?
HIV activists around the world are hopeful that 2020 will finally be the year that the first vaginal ring for HIV prevention, containing dapivirine, an experimental non-nucleoside reverse transcriptase inhibitor, is approved for use by FDA. If—or, when—that happens, it has the potential to be a game changer. A dapivirine ring has been in development for years, but it wasn’t until the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) that encouraging data were seen (dapivirine has never been studied as an oral medication). Results from two Phase III studies—HOPE and ASPIRE—conducted in several African countries showed that the ring is safe and reduced HIV infection by 27–31%. Approximately 2,600 HIV-negative women in Malawi, Uganda, South Africa, and Zimbabwe took part in the studies. For reasons unknown (but quite possibly due to adherence), the ring’s effectiveness was directly associated with the age of study participants. The ring was 0% effective for African women aged 18–21. But efficacy rates rose to 56% for women aged 22–26, and up to 51% for women 27 years and older. Further analysis of ASPIRE and HOPE studies was released at IAS 2019. Deeper analysis showed that women who used the ring regularly had a 65% lower risk of HIV. And efficacy may have as been high as 90% for women with total or near total adherence to the ring.
‘I think telemedicine holds great promise for managing monitoring for [people living with HIV/AIDS], especially those who live in rural areas without access to HIV specialists.’
Many (though not all) people living with HIV who are on treatment have access to their HIV doctors via the internet, especially if they receive their care at a large clinic (such as Kaiser Permanente or a university-based clinic). These clinics offer patient portals where patients can review lab results and other test results such as x-rays or biopsies, ask their doctors non-urgent questions, and request medication refills. It is a great option that certainly is better than waiting around for your doctor to call you back—when your cell phone battery has died, your voicemail is full, or you have no signal (we’ve all been there). What’s the next step? Telemedicine!
Some general medicine clinics are using special software to conduct doctor visits online. This operates like Skype or Apple’s FaceTime, but has a much higher level of security protection and is HIPAA compliant. Telemedicine doesn’t replace an actual physical exam, but could be a great way to discuss results and address questions and concerns.
“I think telemedicine holds great promise for managing monitoring for PLWHA, especially those who live in rural areas without access to HIV specialists,” said Dr. Currier. “The option for video visits is also becoming available at some sites. The willingness of insurance payers to reimburse for these services will be the key driver of whether this practice takes off.”
Telemedicine also has the potential to assist incarcerated PLWHA with their HIV care. Another study presented at IAS 2019 focused on the use of telemedicine in Pennsylvania’s Department of Corrections (PADOC). The Pennsylvania prison system recently changed its approach to HIV treatment. PADOC had previously worked with an in-house infectious disease (ID) program. In 2015, they contracted with a university medical center to create an interdisciplinary team consisting of an ID doctor, nurse practitioner, and ID pharmacist. Using this new model, a retrospective study showed that out of the 227 patients who were involved, approximately 90% got their viral load down to undetectable, and most saw their T cells increase by an average of 40. The telemedicine team also worked with PADOC to help 28 incarcerated patients decrease their pill burden. This meant that 28 incarcerated PLWHA who were previously taking four pills a day to treat their HIV were switched to an STR.
Telemedicine can also be used to assist with PrEP prescriptions via a new platform called MISTR. Available in 44 states at last count, it is accessible on smartphones, tablets, and computers. MISTR allows users to have a video consultation with an HIV doctor (the out-of-pocket fee for potential PrEP patients is $99), do needle-free lab work at home, and have their PrEP delivered free of charge. The program handles all of the paperwork necessary for patients to receive PrEP co-pay assistance, and also works with insurance plans. Given its name, MISTR’s current focus is on MSM, but it plans to also launch a female-focused platform.
An electronic health record can help providers identify people who have been treated for an STI, and that can help lead to a discussion about the possible use of PrEP.
Most medical clinics and private practices have switched from paper charts to electronic health records (EHR). EHR is easy for all of your health care providers to access, and saves paper records from damage by fire, flood, earthquake, and other disasters while being more environmentally friendly. EHR can also be sent easily to a new doctor if you change providers or clinics. But are we using EHR to its full potential? Yet another study out of IAS 2019 doesn’t think so.
A study conducted by Kaiser Permanente in northern California tried to predict HIV rates by reviewing the EHRs of approximately 3.7 million Kaiser members. Patients who were HIV-positive were excluded, as were straight men and MSM who had not been treated for STIs. The study was able to predict HIV infections in 784 people. The next step for researchers will be to evaluate EHR-based risk prediction tools and measure their effect on PrEP prescriptions.
“As we work to expand PrEP to those at risk for HIV, finding ways to identify people at risk is critical,” said Dr. Currier. “An electronic health record can help providers identify people who have been treated for an STI, and that can help lead to a discussion about the possible use of PrEP. Electronic health records are currently used to remind [health care] providers about the need for specific tests and health maintenance. While many providers complain about some of the burdens of EHR, the ability of these kinds of systems to help us improve care are of great value.”
The future has already arrived
Technology is astonishing. Our smartphones are entire computers that we carry in our purses or back pockets. We can communicate with loved ones around the world with the push of a button. Breaking news isn’t hours old—it’s minutes or seconds. And technology is helping combat HIV/AIDS with new potential treatment and prevention advances. Once approved, injectable and implantable treatments will provide more options for patients so that treatment can be customized to meet their individual needs. The addition of a female-controlled prevention tool (like a vaginal ring) will empower women while protecting them from HIV. More targeted use of EHR has the potential to identify those most vulnerable to acquiring HIV and help them access PrEP. All of this thanks to the targeted use of technology. No need to check the date—the future is already here.
Michelle Simek has worked in HIV/AIDS for more than 20 years. She currently works at the UCLA Center for Clinical AIDS Research and Education (CARE) and is a popular HIV/AIDS presenter, both locally and nationally. In her downtime, she is an avid reader and concert goer and proud mom of Baxter, her five-year-old rescue cat.
HIV surveillance and privacy
Data privacy—who has access to your personal information and how it is being used—is an issue in social media, and it’s also drawing growing concern for people living with HIV. The Centers for Disease Control and Prevention (CDC) is examining data from people who are newly diagnosed, without their consent, on the genetic makeup of their HIV. While this data can be used to identify “clusters” of new cases, it raises concerns among advocates.
The Center for HIV Law and Policy (CHLP) in September issued a two-page factsheet, “Is Molecular HIV Surveillance Worth the Risk?” In a factsheet from the CDC, HIV molecular surveillance is described as “the collection, reporting, and analysis of HIV genetic sequences generated through HIV drug resistance testing.” CDC said it uses the information to look for outbreaks. CHLP noted that the CDC has asked local and state health departments to gather community feedback by December. The center organized a webinar on the topic in October. While CDC says health departments do not report names, CHLP raises questions about potential problems such as using surveillance information in HIV criminalization. Read a blog post on this topic by CHLP staff attorney Jacob Schneider at bit.ly/2moMY45; the flyer can be found at bit.ly/2kroK8L. Read the CDC factsheet at bit.ly/2mpwrgj. Go to hivlawandpolicy.org. —Julie Taddeo