ACTG Network at CROI 2018: A Complete Wrap-Up

The ACTG Network was prominently featured at the Conference on Retroviruses and Opportunistic Infections (CROI) 2018 in Boston, Massachusetts. Over 30 oral and poster abstracts were presented by ACTG Network Investigators and many others took part in a variety of panel discussions and workshops over the course of the four-day conference. Numerous media outlets spoke with ACTG Network presenters about important study results regarding A5279, A5257, A5316 and more. The ACTG Network also served as a social media influencer sharing breaking news and important study results.

Women researchers were at the forefront of CROI 2018 with more women than men as lead abstract authors for the first time in its 25-year history. ACTG Network women researchers were interviewed for a video commemorating International Women’s Day and National Women and Girl’s HIV/AIDS Awareness Day. Overall, the presence of the ACTG Network was noticeable and effectively showcased the important work we conduct each and every day.


 

Dr. Judith Currier, ACTG Network Chair and Principal Investigator, Opened CROI 2018

ACTG Network Chair and Principal Investigator, Dr. Judith Currier also served as the CROI 2018 Chair and provided remarks at the conference Opening Session. Dr. Currier noted that CROI 2018 had over 4000 registrants from 78 different countries and over 40 percent of those in attendance were from outside the United States. She reflected on the past 25 years of HIV/AIDS research advancements and noted the need for continued research in the years to come.  To view this presentation, click here.

 

Highlighted ACTG Network Abstract Presentations

A5279
Swindells S., Ramchandani R., Gupta A., Benson C., Leon-Cruz J., Omoz-Oarhe A., Juste M., Lama J., Badal-Faesen S., Moran L., Fletcher C., Nuermberger E., Chaisson R.

One month of rifapentine/isoniazid to prevent TB in people with HIV: Brief-TB/A5279

A5279 received considerable and well-deserved media attention at CROI 2018 with the frequent description of “game changer” related to its findings.  This large multicenter randomized clinical trial found that the incidence of TB disease was similar between HIV-infected participants treated with one month of daily rifapentine and isoniazid compared to those treated with the standard of nine months of daily isoniazid alone.  The one month regimen was also safer with fewer adverse events and higher rates of course completion.  The investigators conclude that this one-month ultra-short course TB preventive course could be an important tool in the global control of HIV-associated TB. To view this presentation, click here.

A5321
Spudich S., Gandhi R., Cyktor J., Lalama C., Bosch R., Macatangay B., Rinaldo C., Robertson K., Collier A., Godfrey C., Hogg E., Eron J., McMahon D., Mellors J.

HIV-1 Persists in Cerebrospinal Fluid Mononuclear Cells in Half of HIV-infected Individuals on Long-term Antiretroviral Therapy.

The A5321 study of participants in ACTG with sustained and documented virologic suppression on long-term ART led to several important abstracts on the HIV reservoir and inflammation.This study found that a high proportion of those with HIV on ART have HIV infected cells detected in cerebral spinal fluid (CSF), presumably due to trafficking into the brain.  In addition, the amount of HIV detected in CSF cells was associated with poorer neurocognitive performance.  This study highlights the importance of the brain as an HIV reservoir. High levels of HIV specific antibodies and T cell responses after long-term ART reflect immunologic sensing of HIV infected cells in the reservoir, but lack of clearance, and targeted interventions are needed to clear, control or reduce the HIV reservoir, especially in the brain. To view this presentation, click here.

A5257
Gandhi M., Ofotokun I., Bacchetti P., Jin C., Ribaudo H., Haas D., Sheth A., Hochster H., Phung N., Kuncze K., Louie A., Okochi H., Landovitz R., Lennox J., Currier J.

Hair antiretroviral (ARV) levels strongly predict virologic outcomes in ACTG A5257.

A5257 was a newsworthy study at CROI 2018 that had two main findings.  First, ART drug levels measured in hair predicts HIV treatment success in a large randomized clinical trial.  The two-year cumulative virologic failure rate was highest (26%) in participants with the lowest levels of drug in hair.  Second, they found that self-reported adherence only weakly correlated with hair levels, suggesting investigators can’t always rely on participant surveys for adherence. Further study is needed to understand how we might use this technology to improve HIV treatment outcomes. To view this presentation, click here.

A5264
Campbell T., Kang M., Umbleja T., Krown S., Bukuru A., Martin J., Godfrey C., Nyirenda M., Busakhala N., Borok-Williams M., Langat D., Hoagland B., Mwelase N., Hosseinipour M.

Predictors of KS-IRIS in mild/moderate AIDS-KS during ART in low-resource settings.

A5264 was an important study focusing on treatment of mild or moderate Kaposi sarcoma (KS)– an HIV-associated cancer globally.  This study assessed cumulative incidence, predictors and outcomes of KS progression during early ART (first 12 weeks), as well as KS immune reconstitution inflammatory syndrome (IRIS).  KS IRIS was common with a cumulative incidence of 23% among those who received only ART and 7% for those given etoposide along with ART.  Predictors of KS IRIS were raised skin lesions, low albumin and low performance status.  Overall KS outcomes after one-year were worse for those with KS IRIS.  Early adjunctive etoposide chemotherapy along with ART reduced all types of KS progression, including KS IRIS, and improved outcomes of this morbid cancer.  This study provides evidence for oncologists to treat mild and moderate KS with chemotherapies earlier than they are currently treating, concomitant with ART. To view this presentation, click here.

A5288
Grinsztejn B., Hughes M., Ritz J., Salata R., Mugyenyi P., Hogg E., Wieclaw L., Gross R., Godfrey C., Kumarasamy N., Kanyama C., Mellors J., Wallis C., Collier A.

A Strategy Study in RLS for 3rd Line ART Candidates.

A5288 was an important study with implications for treatment of HIV in countries with limited resources and limited ART options.  The investigators confirmed that boosted darunavir and raltegravir based ART along with available nucleosides or etravirine were effective third-line ART regimens in resource-limited settings.  When these drugs were used, they achieved viral suppression to <200 copies/mL at 48 weeks in 88-100% of participants.  If second line ART was continued among those with lack of lopinavir resistance and susceptibility to at least one nucleoside, only 44% of patients were virologically suppressed at 48 weeks.  This suggests that resistance was not detected or these participants were simply non-adherent to their second line ART. This sub-group requires further study and possible adherence interventions to achieve viral suppression. Moreover, integrase inhibitor roll-out will be essential for third-line ART in resource-limited settings. To view this presentation, click here.

A5314
Hsue P., Ribaudo H., Deeks S., Lederman M., Fichtenbaum C., Luetkemeyer A., Daar E., Rodriguez B., Taiwo B., Haas D., Johnson V., Stein J., Currier J.

Safety and impact of LDMTX on immune activation and endothelial function in treated HIV: ACTG 5314.

A5314 was a randomized placebo controlled clinical trial testing whether low dose methotrexate reduces inflammation among HIV-infected participants on ART.  This trial has implications beyond HIV medicine as there is a large ongoing study of methotrexate to prevent cardiovascular disease in those without HIV.  In HIV-infected participants over the age of 40 with increased risk for cardiovascular disease, the study team found that those on low-dose methotrexate experienced more adverse events compared to placebo.  Soluble inflammatory markers and endothelial function measured by brachial artery flow-mediated dilation (FMD) were no different between methotrexate and placebo groups after 24 weeks. They noted decreases in CD4+ T cell number, CD8+ T cell number, CD8+ T cell activation and CD8+ T cell proliferation in the methotrexate group compared to the placebo group.  In an A5314 sub-study, there were non-significant decrease in arterial inflammation as measured by FDG PET/CT in 28 participants on methotrexate. The investigators conclude that methotrexate comes with adverse effects, and it is inconclusive if this medication would have any impact on reducing cardiovascular disease for those with HIV. Further evaluation of this agent in HIV will depend on what the large clinical endpoint study in non-HIV reveals. To view this presentation, click here.

A5315
McMahon D., Zheng L., Cyktor J., Aga E., Macatangay B., Rinaldo C., Godfrey C., Para M., Hogg E., Hesselgesser J., Gandhi R., Mellors J.

Single romidepsin infusions do not increase HIV expression in persons on ART (A5315).

A5315 was a placebo-controlled, dose-escalation study of a single dose of romedepsin – a potent histone deacetylase inhibitor previously shown to increase HIV in blood – provide to people living with HIV.  This was an important study in the HIV Cure agenda as investigators examine options to increase expression of HIV hiding out in reservoirs.  In contrast to prior, less controlled studies they found that romedepsin was well tolerated, but it did not increase HIV expression; thus, none of the doses had an impact on HIV activation.  The authors conclude that multiple or higher doses of romedepsin may be required to induce HIV expression. To view this presentation, click here.

A5316
Scarsi K., Cramer Y., Gingrich D., Rosenkranz S., Aweeka F., Coombs R., Zorrilla C., Coughlin K., Moran L., Berzins B., Godfrey C., Cohn S.

Vaginal contraceptive hormone exposure profoundly altered by EFV- and ATV/r-based ART.

A5316 received considerable attention from the press at CROI 2018 as the study has major implications for women living with HIV around the world.  Study investigators found that vaginal ring contraceptive drug concentrations were altered by both efavirenz and boosted atazanavir — two of the most commonly used ARTs worldwide. The researchers concluded from their drug-drug interaction studies that atazanavir/ritonavir is unlikely to impact the effectiveness of vaginal ring contraceptives, but that efavirenz-based therapy may signficantly lower the effectiveness of vaginal ring contraceptives Thus, women on efavirenz-based therapy need to consider alternative contraceptive methods, such as barrier contraception, or other ART such as integrate inhibitors. This drug-drug interaction has the potential to result in unwanted pregnancies. To view this presentation, click here.

A5349
Podany A., Sizemore E., Chen M., Martinson N., Badal-Faesen S., Dawson R., Miyahara S., Whitworth J., Kurbatova E., Chaisson R., Dorman S., Nahid P., Dooley K., Swindells S.

Efavirenz pharmacokinetics in HIV/TB coinfected persons receiving rifapentine.

A5349 was a critical study for countries with a high burden of HIV and TB co-infection.  This was a pharmacologic sub-study assessing drug interactions between efavirenz and rifapentine among participants undergoing TB disease treatment with one of two regimens – daily rifapentine, isoniazid, pyrazinamide, and either ethambutol or moxifloxacin.  The investigators concluded that their drug-interaction studies support the co-administration of high-dose rifapentine and isoniazid with efavirenz containing ART, but further confirmatory research is needed and underway. To view this presentation, click here.

A5282
Wilkin T., Matining R., Sahasrabuddhe V., Chen H., Masih R., Mngqibisa R., Rassool M., Mbilizi Y., Magure T., Riviere C., Asmelash A., Bhosale R., Michelow P., Godfrey C., Firnhaber C.

HPV test & treat vs. cytology-based cervical cancer prevention in HIV+ women.

A5282 was a randomized multinational clinical trial of HIV-infected women with high risk cervical strains of human papilloma virus (HPV).  This study compared two cervical cancer prevention strategies – HPV Test &Treat with cervical cryotherapy OR a single cytologic assessment followed by Loop Electrosurgical Excision Procedure (LEEP) if high-grade abnormalities are detected. The team found similar rates of progression to high-grade squamous cell cervical lesions between these two strategies (21% for HPV Test &Treat and 22% for cytology).  They concluded that HPV Test &Treat potentially did not perform better due to worse responses to cryotherapy in this population and that more effective treatment options are need to improve outcomes of cervical cancer screen-and-treat programs in high HIV burden countries with limited resources. To view this presentation, click here.

A5225
Lalloo UG, Larsen R, Aberg J , Hogg E, Komarow L, Clifford DB, Pillay S, Langat D, Bukuru A, Mave V,  Supparatpinyo K,  Samaneka W

Higher high dose Fluconazole for the treatment of Cryptococcal Meningitis

Induction phase treatment for cryptococcal meningitis (CM) in HIV infected persons is compromised by the lack of and complexity of administering amphotericin B based therapy in many countries therefore a high-dose oral fluconazole 1200 to 2000 mg daily was evaluated in a dose escalation study as induction treatment for cryptococcal meningitis. Persons who received fluconazole 1600 or 2000 mg had better microbiologic outcomes than those who received fluconazole 1200 mg. Overall mortality rates at week 10 were more than 20% among persons receiving 1600 or 2000 mg fluconazole and 19% among those receiving amphotericin B, supporting the newly released WHO guidelines at CROI 2018 for low- and middle-income countries  that no longer recommend fluconazole alone as induction therapy for cryptococcal disease.

 

International Women’s Day 2018 and National Women and Girls HIV/AIDS Awareness Day 2018

Thursday, March 8, was International Women’s Day. To mark the occasion, Infectious Disease News spoke with several ACTG Network women researchers about the role of women in the field of infectious diseases and the hurdles that must be overcome to achieve equality. At CROI 2018 more women than men presented findings at the meeting – a first in the 25-year history of the conference. In fact, the primary authors of 537 of the 990 abstracts that were accepted this year were women.

To view video One, click here.
To view video Two, click here.

Saturday, March 10, was National Women and Girls HIV/AIDS Awareness Day which was created to support women and girls living with HIV and ensure that uninfected women have the knowledge and tools they need to prevent infection. To mark the occasion, Infectious Disease News asked several ACTG Network women researchers what their take-home message is to colleagues, as well as women and girls living with HIV. Recent data show that, overall, new HIV diagnoses are declining among women in the United States. However, more than 7,000 women were diagnosed with HIV in 2016, and certain populations continue to be disproportionately affected by the epidemic, including black women and white women who inject drugs, per the CDC.

To view video One, click here.
To view video Two, click here

 

ACTG Network Media Coverage from CROI 2018

NIAID A5279 Press Release     —     Dr. Richard Chaisson quoted in Science Magazine

Dr. Richard Chaisson quoted in aidsmap     —     Dr. Richard Chaisson and Dr. Constance Benson quoted in MEDPAGE TODAY

Dr. Monica Gandhi quoted in Infectious Disease News     —    Dr. Kimberly Scarsi quoted in aidsmap

Dr. Kimberly Scarsi quoted in MEDPAGE TODAY     —    Dr. Roger Bedimo quoted in aidsmap

Dr. Robert Schooley and Dr. Paul Volberding quoted in MEDPAGE TODAY     —    Dr. Kelly Dooley quoted in Infectious Disease News