Recent Study Results

Since 1987, the work accomplished by the ACTG has had a profound impact on the well-being of people living with HIV. Clinical trials and laboratory studies conducted by the ACTG have made major contributions to optimizing antiretroviral therapy (ART), managing drug resistance, preventing and treating co-infections, evaluating acute and long-term toxicities, and demonstrating the importance of pharmacogenomics in predicting drug toxicities. Results of these studies have helped establish the paradigm for the management of HIV disease and form the basis of current treatment guidelines. This progress in the treatment of people living with HIV has resulted in dramatic reductions in AIDS mortality in the U.S. and other countries of the developed world. Below are some of the results from our most recent studies.

Please click here for a list of some of the most prominent ACTG Abstract Presentations from the 2018 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, MA

 

Other CROI Presentations include:

Category of Trial: Treatment Naïve
Treatment Naïve refers to people who have never taken HIV medications before. These studies are designed to help find out what treatments or drugs work best as an initial regimen.

A5308, A Prospective, Single-arm, Open-Label Study to Evaluate the Effect of Fixed-Dose Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate on T-cell Activation, Absolute CD4+ T-cell Count, Inflammatory Biomarkers and Viral Reservoir in Treatment-naive HIV-1 Controllers, March 2018

The main findings presented in a poster at CROI 2018 included the following: 1) HIV therapy led to some improvements in both markers of immune activation and immune exhaustion; 2) The treatment decreased the small amount of virus that was detectable in the blood before starting therapy; 3) The treatment was well tolerated, and slightly improved quality of life as measured in the questionnaire.

 

A5264, A Randomized Evaluation of Antiretroviral Therapy Alone or with Delayed Chemotherapy versus Antiretroviral Therapy with Immediate Adjunctive Chemotherapy for Treatment of Limited Stage AIDS-KS in Resource-Limited Settings (REACT-KS), March 2018

The main purpose of this study was to find out if taking antiretroviral therapy (ART) together with etoposide (ET) is better than taking ART alone or ART with delayed ET for treating early stage KS.  192 persons participated in this study. A planned secondary purpose of this study was to investigate whether taking ART with ET affected the development KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), which is a common complication of ART for people who have KS.

The study found that 23% of A5264 participants developed KS-IRIS if they were treated with ART alone, and treatment with ART and ET together reduced the occurrence of KS-IRS to 7.4%.  The reduction in KS-IRIS in the ART plus ET arm was statistically significant.  It was also found that the presence of raised skin lesions, low serum albumin and low Karnofsky performance score were potential indicators of higher risk of KS-IRIS during ART.  The conclusion was that KS-IRIS was common among persons with AIDS-KS in low-resource settings after starting ART but that giving ET together with ART reduced the risk of KS-IRIS.

 

Category of Trial: Treatment Experienced
Treatment Experienced refers to people who are currently on medications or have taken medications in the past for HIV. Each study has a unique approach: Which are the best medications to treat with? When is the best time to change medications? How do we know when to change medications?

A5322, “Long-term Follow-up of Older HIV-infected Adults in the ACTG: Addressing Issues of Aging, HIV Infection and Inflammation, March 2018

This study is now in its 4th year of follow-up and has been actively conducting analyses to meet study objectives. The aim of this analysis was to study frailty and disability and how they are related to health outcomes in A5322 participants. Every year A5322 measures frailty and disability. Frailty is measured by collecting five different pieces of information from each participant. These include questions about unintentional weight loss, exhaustion, and physical activity level. Grip strength is measured with a dynamometer (the test device that we ask participants to “squeeze, squeeze, squeeze”) and time a 4-Meter Walk (about 13 feet). Each question and task is scored with points. People with 3 or more points are “frail.” The study measures “disability,” or difficulties with different activities of daily living, by asking questions on 16 different types of tasks people may do as part of daily life. This includes tasks like grocery shopping, driving to work, and keeping track of medications. People with difficulties in at least one of these tasks are considered to have a disability.

It was found that people who were frail had a higher risk of heart disease, but this association was only seen in African-Americans or black persons. It was also found that people who had one or more disabilities had a higher risk of diabetes.

 

A5340, A Phase I, Open-Label Study of the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody, VRC-HIVMAB060-00-AB (VRC01), with Broad HIV-1 Neutralizing Activity, Administered Intravenously to HIV-Infected Adults Undergoing a Brief Analytical Treatment Interruption, March 2018

The aim of this analysis was to examine the effect of a short interruption of antiretroviral therapy (Analytical Treatment Interruption, or ATI) on participant latent reservoir. Several measures of the size of the reservoir and the sequences of viruses from latent virus samples were compared before and 6 months after restarting antiretroviral therapy. The study found that short ATI did not substantially change the size or the composition of the HIV reservoir. This study, in conjunction with several other small studies showing similar results, provides reassurance that short interruptions of therapy in the context of clinical trials are safe for participants.

 

A5325, A Prospective Randomized, Controlled Study to Evaluate the Effect of Isotretinoin on Immune Activation among HIV-1 Infected Participants on Suppressive ART, March 2018

A total of 76 persons participated in this study. The main purpose of this study was to see if taking Isotretinoin, a vitamin A derivative, could have an impact on CD4+ T cell counts and immune activation.  18 persons underwent colonoscopy as part of the A5330s substudy.The results of the study showed that treatment with Isotretinoin increased markers of blood T cell activation while taking the drug. These markers returned to baseline after stopping Isotretinoin. CD4+ T cell numbers in the blood were increased in those who took Isotretinoin versus those who did not. These increases in blood CD4+ T cell numbers were increased even after stopping Isotretinoin, up until week 28, which was the last time blood CD4+ T cell counts were measured. For those who took part in the A5330s substudy, Isotretinoin showed an increase in gut CD4+ T cell division.

 

A5352s, Effects of the Probiotic Visbiome Extra Strength on Epithelial Barrier Function and Inflammation in HIV-Infected Subjects on Suppressive Antiretroviral Therapy: A Substudy of A5350, March 2018

Forty-two participants were enrolled in A5352s, which was designed to look at the safety, tolerability and effects of the probiotic Visbiome ES on the gut inflammation in people infected with HIV.  The main objective of this substudy was to determine whether 24 weeks of Visbiome ES compared to placebo would improve the number of CD4 T cells and/or decrease the inflammation in the gut biopsy samples.

Of the 42 participants enrolled in A5352s, the team had paired before and after gut biopsies from 30 participants, 15 in the Visbiome ES arm and 15 in the placebo arm.  The gut biopsy samples were stained for CD4, IL-17 (a cytokine produced by CD4 T cells, which is thought to protect the gut barrier) and MPO, a marker of inflammation.  The study did not see any significant differences in staining between participants who were on Visbiome ES and those who were on placebo, although CD4 staining appeared to be more stable between the first and second samples in participants on Visbiome ES.

These study results are preliminary and both the parent study, A5350, and the A5352s study teams have several other ongoing analyses to determine the effects of the probiotic, Visbiome, on epithelial barrier function, inflammation, immune function, and symptoms in people living with HIV. 

 

For past results of studies, click here.