Overview: AIDS Clinical Group Network (ACTG), Clinical Trials

1. Overview: AIDS Clinical Group Network (ACTG), Clinical Trials Presenters: Charles ScottAshley YoungJamal H.N. HaileyKen Lazarus Bruce Mandela

2. AIDS Clinical trials group HTTPS://ACTGNETWORKK.ORG The mission of the AIDS Clinical Trials Group (ACTG) Network is: To develop and conduct scientifically rigorous translational research and clinical trials to: • investigate the viral and immune pathogenesis of HIV-1 infection and its complications; • (2) evaluate novel drugs and strategies for treating HIV-1 infection; • (3) evaluate interventions and strategies to treat and prevent HIV-related co-infections and co-morbidity • (4) publish and disseminate results to improve care, and reduce or eliminate morbidity and mortality associated with HIV-1 infection and its complications.

3. Categories of Trials The AIDS Clinical Trials Group (ACTG) conducts a wide range of studies for people infected with HIV. As a matter of practice, the ACTG has developed a core group of ten categories that comprise the bulk of the current trials that are open to enrollment.

4. Categories include: 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. 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? Immunity Enhancers: HIV harms the immune system. These studies look at innovative ways to help your immune system work better while continuing to treat you with HIV medications. Women: Women with HIV have unique gynecology, maternity, and metabolic issues. These studies are dedicated to fostering the health of women. Opportunistic Infections: When people with HIV have an additional infection like cytomegalovirus or tuberculosis, there are important treatment questions and side effects to look for. These studies are looking at that unique situation.

5. Categories continued: Hepatitis: People with HIV may also be infected with Hepatitis. These trials study the treatment of individuals with Hepatitis or individuals with Hepatitis and HIV. Neurologic Complications: HIV infection may cause nervous system problems such as numbness and cognitive problems. These studies look at treatments for the problems. Side Effects: We know that many drugs used to successfully treat HIV have side effects. The following studies look at ways to treat the most common of these side effects. Tuberculosis: People with HIV may also be infected with Tuberculosis. These trials study the diagnosis and treatment of individuals with Tuberculosis. Non-Interventional: Studies in this section are those in which no attempt is made to affect the outcome of HIV treatment, for example, no treatment is prescribed or provided by the study. People who enter these studies may be asked to provide blood or other biological specimens. They may be asked to complete clinical evaluations and questionnaires. The information from these studies might prove useful in evaluating current or future treatment for people living with HIV.

6. A5128 and a5225 A5128: The study will seek Informed consent to use stored specimens for currently unspecified/ genetic analyses. Goal: To develop a standard operating procedure to establish a storage bank for specimens for future genetic (DNA) analyses. A5225: A phase I/II study will compare the standard treatment for CM, amphotericin B with or without flucytosine for 2 weeks, followed by fluconazole for several months to fluconazole only. Goal: To find out whether some dose of oral fluconazole might be as safe and effective as amphotericin B for the treatment of CM. 

7. A5243 AND A5250 A5243:a study to collect blood and saliva samples from former and current participants in AIDS Clinical Trial Group (ACTG) studies at non-U.S. sites. Goal: All samples will be stored for future HIV-related genetic testing. Approval both by the ACTG and by site Ethics Committees will be sought before their use. A5250: Durability of Adherence in Self-Management of HIV (DASH)Stage 1: Participation of enrollees in focus groups to best adapt the Client Adherence Profiling and Intervention Tailoring (CAP-IT) intervention to treatment-naïve participants initiating therapy.Stage 2:Random assignment of HAART naïve individuals to be initiated to either a group that will receive the standard adherence counseling or individualized adherence self-management training. Goal: To learn if individualized adherence self-management training helps HIV-infected individuals take their HIV medicines more consistently and stay on their medication regimens for longer periods.

8. A5264 and A5271 A5264: Compares the effectiveness and safety of ART alone to ART combined with an anti-cancer drug for initial treatment of AIDS related Kaposi’s sarcoma in untreated individuals who haven’t received ART. Goal: ART has been shown helpful in treating KS as well as HIV. It’s designed to help us treat HIV/AIDS related KS in resource limited areas of the world. A5271: Study of healthy HIV-negative people in resource-limited settings. HIV infected people who have started HAART within the last year will participate in focus groups to determine what is needed to help them adhere to regimen. Goal: To learn if individual adherence training helps HIV infected individuals take their HIV medications more consistently.

9. A5273 and A5274 A5273: HIV infected people and their current initial NNRTI containing regimen. Study will compare 2 second line regimens, lopinavir/ritonavir plus raltegravir(LPV/r+RAL) vs LPV/r plus best available NRTIs. Goal: Compare two second line anti-HIV drug regimens to see how well they fight HIV. Will study drug regimen tolerance and their safety. A5274: 2-year study that will test a strategy for reducing early deaths and severe illness among people who are starting HIV treatment in areas with high rates of TB infection. Goal: Whether people living in areas where the rate of TB infection is high, is it better to start anti-TB treatment when they start anti-HIV treatment even though they don’t appear to have TB or if anti-TB treatment should only be started if TB infection is present. Bb

10. A5279 and A5282 A5279: a study comparing the rifapentine plus isoniazid daily for 4 weeks to a standard regimen of isoniazid alone daily for 9 months for the prevention of tuberculosis (TB) in HIV-infected participants who do not show evidence of active TB. Goal: to see which regimen is most effective in TB prevention. A5282: a studying comparing two different methods to prevent cancer of the cervix. Participants will be randomly assigned to one of two different groups. Group 1 will receive cryotherpay and group 2 will receive the standard procedures. Goal: to see which treatment method works better at prevention cervical cancer. This is a test and treat approach in which participants will undgo biopsy.

11. A5288 and A5290 A5288: a study in resource-limited settings to see if HIV-infected persons with two treatment failures will do better in the next treatment if using blood test called a resistance. Goal: The study will look at how well combinations of new anti-HIV drugs work and if taking new anti-HIV drugs together is safe and tolerable. Another question the study wants to answer is whether a certain class of drugs, NRTIs is needed with other anti-HIV drugs. A5290: is a randomized, open-label study comparing three regimens among participants in high TB areas and HIV treatment that includes a protease inhibitor. Goal: To find a safe and effective treatment for TB in persons living with HIV that contains a protease inhibtor.

12. A5294 and A5296 A5294: Research study for people infected with both HIV and Hepatitis C. Goal: Will see if adding third drug BOC to the standard PEG-IFN and RBV is safe and if it will help people with both HIV and HCV better fight HCV. A5296:Sevelamer carbonate will be studied to see how well the drug reduces endotoxin levels and activation of the immune system in people infected with HIV. Goal:See if its possible to reduce the effects of product in the blood and reduce immune activation. 

13. A5298 • A5298: Study of HPV vaccine or placebo in HIV infected men who have sex with men to see if the vaccine prevents persistent anal HPV infection. • Goal: Learn if HPV vaccine prevents persistent anal infection with the four HPV types contained in the vaccine. 

14. A5303: Bone, Immunologic, and Virologic Effects of an ARV Regimen Study Description: A5303 is a study for people who are infected with the R5 type of HIV virus and have never taken HIV medications.  Participants will receive either an experimental regimen (maraviroc [MVC] + emtricitabine [FTC] + darunavir [DRV] + ritonavir [RTV] once-daily) or a standard regimen (tenofovir [TDF] + FTC + DRV + RTV once-daily) for 48 weeks. 

15. A5303 (CONTINUED) Study Goals:The main purpose of the study is to compare the effects of the regimens on bone mineral density (BMD) as measured by a DXA bone scan in patients who have never taken HIV medications. (This study is targeted at the Treatment Naïve population.) The study will also compare the effects of the study drug regimens on changes in the immune system, kidney, bone, and neurocognitive function.   Safety and tolerability of the study drugs and any changes or resistance that occurs in the HIV virus will also be evaluated.

16. A5303 (CONTINUED) Of the more than 47 ACTG sites conducting this study, included are my site in Atlanta, Georgia, • The Ponce de Leon Center (Emory University) and • the University of California, Los Angeles CARE Center CRS 

17. A5306: Safety and Drug Interaction Study of PA-824 together with Select Drugs for the Treatment of HIV or Tuberculosis Study Description This is a study in healthy HIV-negative participants to look at interactions and safety of different drug combinations: PA-824 (a new anti-tuberculosis drug) and efavirenz (EFV), lopinavir/ritonavir (LPV/r) [approved anti-HIV drugs] or rifampin (RIF) (an approved anti-tuberculosis drug). Why is this study being done?To measure the combination of two medications at different times in the blood and to see how safe and easy they are to take together.

18. A5308: Open-Label Study to Evaluate the Effect of Fixed-Dose COMPLERA (Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate) in Treatment-Naïve HIV-1 Controllers • Study Description A5308 is a study for HIV-infected individuals who have low HIV-1 viral loads (less than 500 copies) and have never taken HIV medications.  These individuals, who are called HIV controllers, do not show any signs of having HIV and are doing well without taking HIV medication. All participants will receive fixed-dose Complera (brand name) for 48 weeks and will then be given the choice to continue taking Complera or stop taking the medication. • Study Goals The purpose of this study is to see if taking HIV medication will reduce immune activation (body’s way of fighting disease) in people who have HIV but do not show symptoms. An optional viral decay component will help determine how quickly HIV-1 virus is eliminated from the blood after starting medication.

19. A5308 (CONTINUED) Of the more than 31 ACTG sites conducting this study, included are my site in Atlanta, Georgia, The Ponce de Leon Center (Emory University) and the University of California, Los Angeles CARE Center CRS

20. References Page All information was taken from AIDS Clinical Trails Group webpage. -https://actgnetwork.org/open_and_enrolling_studies