Wits Health Consortium, t/a Clinical HIV Research Unit
Helen Joseph Hospital, Themba Lethu Clinic
A5409: A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (RAD-TB)
The standard of care (SOC) treatment of tuberculosis (TB) was developed over 40 years ago, and the treatment is long (6 months) and hard. In many settings, the medicine does not work well because people stop taking it or miss doses, which leads to TB returning. For some people, the SOC treatment can cause negative side effects.
This study will evaluate new medication regimens for the treatment of TB. This study is adaptive, which means, as new medication regimens are identified for the treatment of TB, some of them will be selected for testing in this study. Therefore, there may be different drug regimens being used as part of the study at different times.
A5417: Randomized, Double-Blind, Placebo-Controlled Study of the Combination of two Long-Acting Broadly Neutralizing Antibodies at ART Initiation in Adults Living with HIV-1 in sub-Saharan Africa
This study enrolls people living with HIV in sub-Saharan Africa at the time that they are about to start antiretroviral therapy (ART). They will be assigned to receive either two long-acting study medications called “monoclonal antibodies” or placebo (normal saline) when they start ART. An antibody is a substance that the body makes in response to an infection. The antibodies in this study attach to HIV and can block HIV from attacking cells in the body and from spreading to other parts of the body. These study antibodies are being developed to potentially treat and prevent HIV.
A5397/HVTN 603:A Phase 2a/2b Study Evaluating Safety, Immunogenicity, and Therapeutic Efficacy of ID93 + GLA-SE Vaccination in Participants with Rifampicin-Susceptible Pulmonary TB
Effective tuberculosis (TB) treatment is available and saves millions of lives, but it has not had a significant impact on the global TB epidemic. The treatment requires strict adherence to taking the medicine on schedule, and if it isn’t taken as directed people can relapse before they complete treatment. TB can recur in up to 8% of people who successfully complete TB treatment. Having an effective TB vaccine to prevent TB infection and control TB disease is essential to eliminate TB globally.
A5397/HVTN 603 will give participants 2 injections of a study vaccine called ID93+GLA-SE or a placebo at different times after they have started taking TB treatment. The researchers will compare responses in people who get the study vaccine to people who get the placebo. This study will enroll both people with and without HIV. It is the first to test ID93 + GLA-SE in people living with HIV (PLWH).
A5385: An Observational Post-Intervention Cohort Destination Protocol
This study is a two-step, non-interventional extension study for individuals participating in another interventional HIV cure trial (parent study) that includes an analytical treatment interruption (ATI) (stopping anti-HIV therapy [ART] while monitoring viral load). Participants will be individuals who achieved post-intervention control (PIC) (maintaining HIV suppression after treatment interruption) in their parent study.
Step 1 will consist of an extended ATI period in which PICs will be monitored for safety, viral, and immune outcomes. Time to viral rebound and restart of antiretroviral therapy (ART) will be measured. Participants will begin Step 2 if they meet ART restart criteria and will be monitored for safety, immune, and viral outcomes through 48 weeks after ART restart.
A5354: Effect of Antiretroviral Treatment Initiated During Acute HIV-1 Infection on Measures of HIV-1 Persistence and on HIV-1-Specific Immune Responses
Will evaluate whether starting antiretroviral drugs very early in HIV infection will limit the virus from getting into hidden areas of the body (reservoirs) and change how the immune system helps to control the virus.
This study will include people who have very recently been infected with HIV and will start anti-HIV (antiretroviral) drugs right away to see how this may change HIV’s impact on the body.
A5321: Decay of HIV-1 Reservoirs in Participants on Long-Term Antiretroviral Therapy: The ACTG HIV Reservoirs Cohort (AHRC) Study
AHRC (pronounced “ARC”) is a study of differences and changes over time in HIV reservoirs (groups of HIV-infected cells that “hide” from anti-HIV medications). This study enrolls people into one of six groups, based on their different HIV treatment histories. The current version of this study is only enrolling for Group 6, which will include people who acquired or are suspected to have acquired HIV while taking long-acting cabotegravir (LA CAB) for pre-exposure prophylaxis (PrEP).
HIV comorbidities and complications
A5243: Non-US Genomic Sampling
Collecting blood and saliva samples from former and current ACTG study participants for future HIV-related genetic testing.
This is 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.
HIV comorbidities and complications
A5332: REPRIEVE Trial
In this study, people between the ages of 40 and 75 with HIV will be randomized (like flipping a coin) to take the pill pitavastatin OR a placebo (non-active pill) to see if pitavastatin can help prevent heart disease and death in people who are taking HIV medication. You will not know if you are taking pitavastatin or placebo. The REPRIEVE trial will enroll about 7500 people from several countries.
A5381: Observational Cohort to Assess Therapeutic Efficacy and Emergence of HIV Drug Resistance Following Initiation of Tenofovir-Lamivudine-Dolutegravir (TLD) for First- or Second-Line ART
This is a study for people who have HIV and qualify to switch to or receive Dolutegravir containing antiretroviral therapy (ART, group of medicine used to treat HIV). Taking TLD (combination pill of three medicines for HIV, tenofovir-lamivudine-dolutegravir) has shown to be better tolerated, work better against the virus known as virologic efficacy, have fewer drug-drug interactions, and have less frequent onset of HIV drug resistance than Efavirenz containing ART. In August 2017, a decision was made to start using TLD for first- and second-line ART in many places in the world. This study is designed to help us understand the risks and benefits of TLD roll-out in low- and middle-income countries that may not use viral load testing and HIV resistance testing (a way to measure if a drug will work against your HIV) to guide ART management. Each participant will be assigned to one of four groups:
- Group 1: Participants switching to TLD, after taking prior anti-HIV medication that contains a NNRTI drug (a group of medicines scientifically known as non-nucleoside reverse transcriptase inhibitors, such as Efavirenz or Nevirapine).
- Group 2: Participants switching to TLD, after taking anti-HIV medication that contains a PI drug (a group of medicines scientifically known as protease inhibitors, such as Lopinavir or Atazanavir).
- Group 3: Participants taking TLD and receiving medication for TB (tuberculosis) that includes the drug rifampicin. These participants must be starting one or both of these medications when they enter the study.
- Group 4: Participants starting TLD who have not taken anti-HIV medication before.
There will be 1350 participants enrolled in the study.
A5300B/I2003B: Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)
This trial is in household contacts (HHC) at high risk for developing multidrug resistant tuberculosis (MDR-TB) which is an infection that does not get better with standard treatment for TB. HHC means any person that lives with, has lived with, or shared housekeeping duties in a home or the same place with a person (an Index Case) who has pulmonary MDR-TB (a lung infection or pneumonia with TB) and started treatment for MDR-TB within the past 90 days. It is also for people who have spent more than 4 hours indoors with the index case, during the week before they started MDR-TB treatment.
High-risk household contacts are those with HIV or an immune system problem not from HIV like cancer , latent TB infection (a history of TB infection in the past based on testing), and young children below the age of 5 years.
A5379: B-ENHANCEMENT OF HBV VACCINATION IN PERSONS LIVING WITH HIV (BEe-HIVe): Evaluation of HEPLISAV-B
A5379 is a study looking at hepatitis B vaccination in adults living with HIV. Hepatitis B is a serious viral infection that affects the liver and is transmitted through blood and body fluids. The study will involve individuals who have received a previous hepatitis B vaccination but the vaccine did not respond well and individuals who have never received the vaccination. The study will take place both in the US and internationally. The study will compare how well an individual responds to the vaccine in different groups based on the type of vaccine and number of doses.