The future is already here

“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.”

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.