New IDSA Guidance for HIV Primary Care is Testament to Antiretroviral Therapy

On November 7, 1991, professional basketball star Magic Johnson announced to the world he was HIV positive. His public statement was covered in a national press conference, and at the time, many people speculated he would eventually succumb to the virus.

During the early years of HIV/AIDs, clinicians had nothing in their armamentariums to treat their patients. And much like COVID-19 patients today, a great many were dying in isolation in the hospital back then.

“The HIV patients, early on, were dying alone. Because of stigma, discrimination, and unjustified fear, they were shunned by friends and family. And of course, early on, we had no therapies,” David Ho, MD, HIV pioneer researcher told Contagion® of the days before the development of antiretroviral therapy (ART).

Just a few years after Johnson’s announcement, the launch of ART for people with HIV (PWH) began. This therapy would eventually transform HIV/AIDS from a disease that an overwhelming majority of people would die from, into a chronic condition for much of this patient population.

Led by researchers such as Ho, the ART 3-drug anti-HIV cocktail therapies saw the mortality rates drop precipitously and it became a game changer for PWH, including Johnson who is alive today.

“Antiretroviral therapy has been nothing short of revolutionary,” Melanie Thompson, MD, principal investigator of the AIDS Research Consortium of Atlanta (ARCA), stated.

“It has become a chronic disease as long as it is diagnosed and properly treated,”Pedro Cahn, MD, scientific director, Fundación Huésped, professor of Infectious Diseases, Buenos Aires University Medical School, added.

Now with an aging population of PWH, the conversation has changed from one of keeping people alive to now potentially treating them for age-related conditions. Therefore, it is fitting that nearly 30 years to the day after Johnson’s announcement, and almost 25 years after the introduction of ART, that on November 6, 2020 an expert panel from the Infectious Diseases Society of America (IDSA) launched an update to the organization’s 2013 primary care guidance.

“Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a near expected life span, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the life span,” wrote the authors in the guidance.

This guidance, Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America, which was published in the organization’s journal, Clinical Infectious Diseases, is a resource to provide comprehensive evidence-based primary care to people with HIV.

Thompson was part of the HIV Medical Association (HIVMA) panel that developed the IDSA guidance and the lead author for the subsequent paper. She has a storied background in HIV including being the principal investigator of the AIDS Research Consortium of Atlanta, through which she has conducted over 400 studies of HIV, STDs and viral hepatitis; a member of the National Institutes of Health Office of AIDS Research Therapeutics Research Working Group; and on the Board of Directors of HIVMA.

The HIVMA panel conducted a review of the literature to identify contributions to the field over 6 years from the date of the 2013 guidance until December 2019. The panel added small exceptions including the Centers for Disease Control and Prevention (CDC)/Advisory Committee on Immunization Practices (ACI) guidelines, which came out in January of this year and coronavirus 2019 (COVID-19) comments that included peer-reviewed presentations at recent scientific conferences.

The panel’s work led to a comprehensive guidance, which is broken up into 9 sections and covers all ages from children through older adults and includes sections for cisgender women and transgender men. It also includes a section on COVID-19 and PWH.

“In addition to dealing with HIV, and management of antiretrovirals we have to be sure that people with HIV get holistic care,” Thompson explained. “Our guidance really begins there.”

Aging Adults

One of the unique sections within the guidance is the one that pertains to older adults.

The guidance notes that approximately 50% of the global population with HIV is around 50 years old and that this PWH cohort is now at increased risks of age-related comorbidities.

“We know that when people access antiretroviral therapy, can have continuous access, and can keep their HIV suppressed, they can live a near normal lifespan.” Thompson said.

As such, the primary care guidance covers areas including dyslipidemia, diabetes, bone mineral density, hypogonadism, vitamin D, and neurocognitive disorders.

A Dichotomy of HIV Care

Sadly, one of the distinctions of PWH is the dichotomy between those with access to care and those who do not. Thompson talks about the continuum of care challenges between the 2 cohorts. In the one group, PWH have access to care, ART, and are the population who is getting older and dealing with age-related issues like comorbidities, frailty, and neurocognitive decline.

The second group, however, is not reaping the benefits. In this cohort, it is striking how the lack of care leads to a stark difference in their outcomes. This second group is dealing with social inequities and make up a much younger, very different socioeconomic group.

“Ending the HIV epidemic, however, has proven challenging in the United States, with only 59.8% of those aware of their HIV diagnosis achieving viral suppression, and even lower rates among African-Americans, Hispanic/Latinos, transgender women, persons aged 13–24 years, persons who inject drugs (PWID), and those who live in the South,” the authors wrote.

And while many in the public view HIV and AIDS as a chronic condition today, there is still cause for concern. Approximately 13000 Americans die from it annually according to the Kaiser Family Foundation

“The other world where I live in Georgia, people are still dying from AIDS,” Thompson said. “It is not as if we have conquered HIV…We have people hospitalized with the old AIDS infections and malignancies that have almost been eliminated by antiretroviral therapies. If you look at the populations who continue to be the most affected, they are driven by factors such as structural racism, stigma, discrimination, and lack of access to social services.”

The primary care guidance looks to address those who are marginalized and includes sections for cisgender women and transgender men.

Thompson also explains it was important to think about how do we get these PWH access and think about the continuum of care for them.

“We begin our guidance with a section about care because we really have to optimize our care engagement strategies to help people and reach the populations that has fewer resources,” Thompson said. “We recommend that clinics tailor their services to people who have fewer resources.”

She said this can include people who may not have a car to drive to the clinic or the ability to go to the clinic during a weekday so to offer rides when possible and night or weekend clinic hours.

The guidance also recommends care services that are welcoming to help PWH continue their care. This can include culturally and linguistically appropriate signage, recommended Thompson.

And while they would like to see a multidisciplinary approach to patient care, the guidance recommends a single care provider so a relationship can be built between the clinician and the PWH.

The Next Generation of ART

As with all therapies, pharmaceutical companies are refining their existing ART agents or developing new ones to address potential health issues.

“We are seeing newer, long-acting agents in clinical trials,” Thompson stated. “This can simplify therapy and help with adherence issues.”

One area within ART that is being studied is polypharmacy. For example, ViiV Healthcare’s GEMINI studies looked at dolutegravir plus lamivudine (Dovato) in possibly reducing a 3-drug regimen down to 2. Dovato was approved by the US Food and Drug Administration (FDA) in the spring of 2019.

Cahn was a principal investigator in the GEMINI study program. Long-term findings over 3 years demonstrated that dolutegravir plus lamivudine continued to offer non-inferior efficacy, a high genetic barrier to resistance and a comparable safety profile versus a 3-drug regimen of dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve adults with HIV, according to the results from the phase 3 GEMINI 1 and 2 studies presented virtually at HIV Glasgow 2020.

“Dolutegravir plus lamivudine continues to demonstrate long-term non-inferior efficacy compared to dolutegravir plus TDF/FTC with benefits beyond viral suppression,” Cahn said. “While overall adverse event rates were similar across the study arms, we saw fewer drug-related adverse events with dolutegravir plus lamivudine. Clinicians who wanted proof that a dolutegravir-based 2-drug regimen works long-term in treatment-naïve adults with HIV now have evidence to show that it does.”

Cahn uses the example of a young person who gets diagnosed today and could be looking at decades of ART. He says it is better to have that PWH on a dual therapy to start.

“We demonstrated the last proof of concept that we needed,” Cahn said as one of the important takeaways from the GEMINI studies. “Dual therapy can be as good as triple therapy. The gold standard for treating patients with HIV was 3 drugs…we have now shown you can do the job with 2.”

The Gains and The Challenges that Remain

Thompson believes it is important to strike the right tone in understanding how far HIV care has come, but that there are still those left behind.

“It is really important to balance these terrific advances we have made with the fact that it is entirely unacceptable that many of our population are not going to benefit,” Thompson stated.

While challenges including adherence, social determinants, and a now aging PWH population remain, the hope is that the new HIVMA primary care guidance and the continuation of ART developments will work towards addressing these existing issues and a larger number of people being successfully treated in their continuum care.