This has been a busy year for research and drug development in the HIV space. Broadly, there were new drug approvals and advances in treatment throughout 2018, as well as many studies about comorbid conditions that people with HIV might face.
Approvals and Advances in HIV Treatment
This was a year full of approvals for HIV drugs and combination antiretroviral treatments. The US Food and Drug Administration (FDA) approved new combinations as well as expanded indications to provide more options for providers as they find the treatment regimens best suited for each patient’s needs.
Early on this year, the FDA approved a combination of bictegravir, emtricitabine, and tenofovir alafenamide(Biktarvy). The once-daily tablet is indicated for adults with HIV-1 who are either treatment-naïve or who have reached virologic suppression and have been on a stable antiretroviral treatment (ART) regimen for at least 3 months without a history of treatment failure nor known resistance to components of Biktarvy.
Shortly after, the FDA approved ibalizumab (Trogarzo), a new treatment indicated for patients with multi-drug resistant HIV infection. Ibalizumab had previously been granted fast track, priority review, orphan drug, and breakthrough therapy designations. Ibalizumab has also been shown to be effective for patients with multi-drug resistant HIV infection.
“Trogarzo is the first drug in a new class of antiretroviral medications that can provide significant benefit to patients who have run out of HIV treatment options,” said Jeff Murray, MD, deputy director, Division of Antiviral Products, FDA’s Center for Drug Evaluation and Research, in a statement at the time of ibalizumab’s approval.
A group of 3 similar HIV antiretroviral regimens were approved during the first quarter of 2018 as well. The combination of lamivudine and tenofovir disoproxil fumarate (Cimduo) was approved in late February. Symfi Lo and Symfi, both combinations of efavirenz, lamivudine, and tenofovir disoproxil fumarate, were also approved in Q1. Symfi Lo contains 400 mg efavirenz while Symfi contains 600 mg. Both contain 300 mg each of lamivudine and tenofovir disoproxil fumarate.
In July, the FDA approved Symtuza as the first single-tablet regimen based on darunavir. The antiretroviral treatment also contains cobicistat, emtricitabine, and tenofovir alafenamide. Symtuza is approved for adults with HIV-1 infection who are either treatment-naïve or who are virologically suppressed, have been on a stable antiretroviral regimen for ≥6 months, and have no known substitutions associated with resistance to either darunavir or tenofovir.
Most recently, the FDA approved doravirine (Pifeltro) a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a combination therapy consisting of doravirine, lamivudine, and tenofovir disoproxil fumarate (Delstrigo). Both are indicated for treatment-naïve adults with HIV-1 infection.
While not a new approval, in May, the FDA expanded the indication for the HIV pre-exposure prophylactic (PrEP) Truvada (emtricitabine and tenofovir disoproxil fumarate) to include adolescents at risk of contracting HIV infection.
Lastly, a vaccine, another avenue for HIV prevention, has received some attention in 2018. Investigators at the University of Massachusetts, led by Shan Lu, MD, PhD, have begun a phase 1 clinical trial to test the safety of an HIV vaccine. While an HIV vaccine has been elusive so far, the Lu said his vaccine is unique because it is a DNA vaccine followed by a booster protein vaccine.
New Research on Comorbidities for Patients with HIV
As antiretroviral therapies improve and people with HIV live longer, there are more cases of comorbidities and concerns for the increased risks HIV infection can bring. Over the past year, several studies have delved into the intersection of HIV and various cardiovascular conditions, cancers, and infectious diseases.
The antiretroviral treatment regimens that people living with HIV must take indefinitely can take a toll on the body. One study found that cumulative use of darunavir, a protease inhibitor, was associated with increasing risk of cardiovascular disease, while cumulative use of atazanavir was not. The prospective study looked at cardiovascular outcomes including myocardial infarction, stroke, sudden cardiac death or use of invasive cardiovascular procedures. Another study using the same cohort of participants found that antiretroviral treatments are not the cause of the higher prevalence of hypertension among persons living with HIV.
A study of children with perinatally acquired HIV infection found that patients taking combination antiretroviral regimens with protease inhibitors had significantly better cardiac function than those receiving other combination antiretroviral treatments. However, no individual antiretroviral drug was shown to affect measures of left ventricular function.
Other studies looking at cardiovascular health have found that the long-term inflammation caused by HIV infection directly impacts cardiovascular health, and that HIV infection does not increase the risk of recurrent acute coronary syndrome.
In the area of oncology, while people with HIV have a higher risk of cancer, research has shown that viral suppression through antiretroviral treatments reduces the risk of cancer. In another study, investigators found a significant association between lung cancer mortality and HIV infection.
A small study presented at the European Society for Medical Oncology’s ESMO 18 Congress in Munich showed that immunotherapy for cancer is safe in patients with HIV who are taking antiretroviral therapy. While the results need confirmation, they are promising, particularly for patients who face AIDS-defining cancers.
In the infectious disease realm, new research during 2018 showed that hepatitis C infection increased mortality for people with HIV by 4.3% (95% CI .4–8.9%) with a risk ratio of 1.4 (95% CI, 1.0-1.9%), even with antiretroviral treatment. However, treating the hepatitis C infection with direct-acting antivirals, the risk difference for patients treated with DAAs was -3.8% (95% CI -9.2–.9%) with a risk ratio of .8 (95% CI .6–1.1).
Investigators researching outcomes for HIV-exposed infants found that those who became infected in utero had a 23% risk of contracting cytomegalovirus (CMV), while those who became infected during birth had a 9.1% chance of getting CMV. Of infants who were HIV-exposed but uninfected, 4.9% were infected with CMV.
Another study of infectious disease comorbid with HIV infection examined different treatment regimens for tuberculosis in people living with HIV. Investigators found that a 1-month antibiotic regimen was at least as safe and effective as a standard 9-month regimen. Additionally, adherence was higher among patients in the 1-month treatment arm.
Looking Ahead to 2019
Despite a year full of new antiretroviral treatments and research, many questions remain for investigators to puzzle out. Especially promising are the clinical trials of different HIV vaccines. In the meantime, the multitude of available ART mean that providers can help find the best treatment regimens for more and more people living with HIV.
Much more remains to be done to increase viral suppression and prevent HIV infections, but one bright point of research published this year was a study of HIV viral suppression rates in the United States. Investigators found that from 1997 to 2015, viral suppression rates for HIV nearly tripled from 32% to 86%.
By Cecilia Pessoa Gingerich