Combination Therapy for HIV/AIDS

Overseen By Steven G Deeks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Francisco

Must be taking: Antiretrovirals

Must not be taking: Non-nucleoside reverse transcriptase inhibitors

Disqualifiers: Pregnancy, HIV malignancy, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 34 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether a combination of therapies can control HIV without ongoing antiretroviral treatment. Researchers test this approach by administering a set regimen to participants on stable HIV medication, then pausing their usual treatment to observe the effects. It targets individuals living with HIV who have been on continuous antiretroviral therapy for at least a year and maintain a stable, low viral load. The trial is not suitable for those with certain medical conditions or using specific HIV medications. As a Phase 1 and Phase 2 trial, it focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires participants to stay on their current antiretroviral therapy (ART) without changes during the study period, as long as it does not include a non-nucleoside reverse transcriptase inhibitor (NNRTI).

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combination therapy for HIV/AIDS is promising in terms of safety. In one study, the combination of BIC/FTC/TAF proved safe and well-tolerated over 48 weeks, effectively controlling the virus without negatively impacting metabolism.

Another study found that certain HIV drug combinations, such as raltegravir and ritonavir-boosted lopinavir, were both safe and effective. Patients experienced similar virus control and improvements in immune cell counts compared to other treatments.

Overall, these findings suggest that the combination treatment under investigation has a strong safety record in previous studies. However, as this trial is in its early stages, the full safety profile is still being assessed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination therapy for HIV/AIDS because it integrates multiple approaches to tackle the virus more effectively than current treatments. While standard HIV treatments typically involve antiretroviral therapy (ART) that targets viral replication, this new combination therapy aims to enhance the immune response and improve long-term viral suppression. By potentially involving innovative agents or mechanisms that work synergistically, this treatment could offer a more robust defense against HIV, leading to better patient outcomes and possibly reducing the risk of drug resistance.

What evidence suggests that this trial's treatments could be effective for HIV/AIDS?

Research shows that using a combination of drugs to treat HIV is highly effective. Since 1996, studies have found that taking three antiretroviral drugs together is key to successfully managing HIV. This method has greatly reduced the virus in the body and lowered death rates for those with severe cases. Recent evidence indicates that even using two drugs together can control the virus in 99% of patients. This combination approach is crucial because it controls the virus better than using a single drug. Participants in this trial will receive a combination intervention to evaluate its effectiveness in managing HIV. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults under 67 with HIV who've been on stable antiretroviral therapy without interruptions for at least a year. They must have a strong immune system (CD4+ T-cell count ≥ 500 cells/mm3) and undetectable HIV levels for the past two years. Excluded are those with certain medical conditions, recent cancers, low CD4+ counts during chronic infection phase, active hepatitis B or C, pregnancy, or resistance to specific antibodies.

Inclusion Criteria

I am 67 or younger, starting treatment early, or under 65 if starting late.

Willing and able to provide written informed consent

Documented HIV-1 infection

Exclusion Criteria

I have an active hepatitis C infection.

I haven't had or expected to have cancer treatment, except for HIV-related, in the last 3 years.

My tests show high resistance to specific treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination regimen including IL-12 adjuvanted p24CE DNA prime, DNA boost, MVA/HIV62B boost, bNAbs, and TLR9 agonist

34 weeks

Multiple visits for administration of vaccines and antibodies

Analytic Treatment Interruption (ATI)

Participants undergo ATI with monitoring of viral load and administration of bNAbs

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment interruption

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Combination Intervention

Trial Overview

The study tests a combination treatment aimed at controlling HIV without ongoing medication. Twenty participants will receive this regimen while on their usual antiretroviral therapy (ART), followed by a period where ART is paused to see if the virus remains controlled.

How Is the Trial Designed?

Group I: Combination intervention arm Experimental Treatment 1 Intervention

All volunteers will receive the combination intervention outlined above.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Mologen AG

Industry Sponsor

Trials

7

Recruited

770+

International AIDS Vaccine Initiative

Collaborator

Trials

52

Recruited

13,300+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

GeoVax, Inc.

Industry Sponsor

Trials

6

Recruited

440+

amfAR, The Foundation for AIDS Research

Collaborator

Trials

29

Recruited

6,200+

Rockefeller University

Collaborator

Trials

162

Recruited

16,700+

Ichor Medical Systems Incorporated

Industry Sponsor

Trials

11

Recruited

440+

Ichor Medical Systems

Collaborator

Trials

1

Recruited

10+

Published Research Related to This Trial

In a study of 1160 patients on antiretroviral treatment for HIV-1, 47% experienced clinical adverse events and 27% had laboratory adverse events linked to their treatment, highlighting a significant prevalence of side effects.

The research found that more complex treatment regimens, such as dual-PI and three-class antiretroviral treatments, were associated with a higher likelihood of adverse events compared to simpler single-PI treatments, indicating the need for careful monitoring of patients on these regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study. Fellay, J., Boubaker, K., Ledergerber, B., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2920287/

The effect of combined antiretroviral therapy on the overall ...

We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/7811541/

Combination therapy: more effective control of HIV type 1?

Clinical results available to date indicate that drugs should be given simultaneously for optimal benefit. There appears to be a rationale for early initiation ...

3.

nejm.org

nejm.org/doi/full/10.1056/NEJM200103153441108

The Cost Effectiveness of Combination Antiretroviral ...

A three-drug regimen of combination antiretroviral therapy for HIV disease has been proved to be clinically effective. ... The results of ongoing ...

4.

aidsmap.com

aidsmap.com/news/may-2023/real-world-data-confirm-efficacy-dolutegravir-based-dual-therapy

Real-world data confirm the efficacy of dolutegravir-based ...

Of the people who switched to or continued on a two-drug regimen, 99% achieved or maintained viral suppression. Although representing a minor ...

5.

thelancet.com

thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00249-1/abstract

Two-drug regimens for HIV treatment

Combination therapy with three antiretroviral agents has been integral to successful HIV-1 treatment since 1996. Although the efficacy, adverse effects, ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39564653/

Effectiveness, safety, and patient-reported outcomes of ...

BIC/FTC/TAF demonstrated high persistence, safety, virological efficacy, and favorable metabolic profile over 48 weeks.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8931831/

Effectiveness and Safety Analysis of PIs/r Based Dual ...

The aim of this study is to evaluate the effectiveness and safety of PIs/r-based dual therapy in treatment-naïve HIV/AIDS patients by using network meta- ...

8.

academic.oup.com

academic.oup.com/ofid/article/11/11/ofae618/7823620

Results Through Week 144 of the SIMPL'HIV Trial | Open ...

The study demonstrated that viral suppression, CD4 gains, adverse events, quality of life, and patient satisfaction were comparable between ...

9.

thelancet.com

thelancet.com/journals/lanhiv/article/PIIS2352-3018(24)00085-7/fulltext

Efficacy and safety of three antiretroviral therapy regimens ...

The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future ...

10.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00006339

Safety and Effectiveness of an Anti-HIV Drug Combination ...

The purpose of this study is to compare the safety and effectiveness of an anti-HIV drug combination with and without hydroxyurea in patients with early HIV ...