Changes in Immunologic Parameters Following the Addition of Fostemsavir in Virologically Suppressed Immunologic Non-responders Living With HIV-the RECOVER Study

  • days left to enroll
  • participants needed
  • sponsor
    Orlando Immunology Center
Updated on 11 October 2022


The RECOVER study is a self-controlled case series to evaluate whether the addition of Fostemsavir (Rukobia) to a stable HIV regimen in virologically suppressed patients living with HIV who never experience optimal CD4 T-cell count recovery can result in meaningful increases in different immunologic parameters such as CD4 T-cell count, CD4 T-cell percentage and CD4/CD8 ratio


In July 2020 the FDA approved fostemsavir (FTR), a prodrug of its active moiety temsavir which is a first-in class attachment inhibitor to be used in combination with other antiretrovirals (ARVs) to treat HIV infection in patients with multi-class drug resistance who are failing their current ARV regimen [1]. FTR is well-tolerated, dosed orally twice-daily, has no food requirement, no need for renal or hepatic dose adjustment and few drug-drug interactions (DDIs) [1-3]. FDA approval was based on 96-week data from the BRIGHTE study which demonstrated that addition of FTR to an optimized background regimen (OBR) among patients with multi-drug resistance failing their current regimen resulted in 96-week virologic suppression rates of 60% among patients with 1-2 fully active ARV classes remaining at baseline (randomized cohort) and 37% among patients with 0 fully active ARV classes remaining at baseline (non-randomized cohort) [4]. Robust CD4+ T-cell recovery was observed with a mean increase of 90 and 205 cells/mm3 through Weeks 24 and 96 respectively among patients in the randomized cohort [4]. The gain in CD4+ T-cells was however most impressive among the most immunocompromised patients, at Week 96 a mean increase of 240 cells/mm3 was observed among those with baseline CD4+ T-cell counts <20 cells/mm3 and 56% of patients with baseline CD4+ T-cell counts <50 cells/mm3 had achieved a CD4+ T-cell count of ≥200 cells/mm3 [4].

These data have raised questions about whether FTR has the ability to promote CD4+ T-cell recovery independently of HIV viral suppression. This first-in-class attachment inhibitor has a unique mechanism of action, the active moiety temsavir binds directly to viral gp120 preventing HIV-1 from interacting with the host immune cell. This process leaves the CD4+ T-cell untouched and it is hypothesized that temsavir binding to gp120 inhibits gp120-mediated apoptosis of CD4+ T-cells and does not allow for activation of other downstream inflammatory pathways that may contribute to CD4+ T-cell death [2]. Other clinical trials of ARVs used in heavily-treatment experienced populations, including those with ibalizumab, dolutegravir, enfuvirtide, maraviroc and etravirine have not demonstrated the degree of CD4+ T-cell recovery observed in the BRIGHTE study [5-9]. Cumulatively these data suggest that FOS may be of benefit in individuals who experience suboptimal immunologic recovery despite achieving viral suppression also known as immunologic non-responders (INRs).

Since 1997, researchers have struggled to identify agents that can restore CD4+T-cell counts and reduce immune activation and inflammation in virologically suppressed INRs [10]. Despite achieving ARV efficacy, this group continues to be at higher risk of disease progression to AIDS, complications related to opportunistic infections (OIs) and death [10, 11]. Recently, data has also revealed that persistent immune activation and inflammation also contributes to higher rates of non-AIDS related events such as hypertension, hyperlipidemia, hyperglycemia and cardiovascular disease [11]. Multiple strategies to address CD4+ T-cell depletion and persistent immune activation among INRs have been investigated over the years, these include the use of adjunctive maraviroc, immune modulators, statins, sitagliptin, niacin, antivirals, nutritional supplements and growth hormone in combination with ART [10, 12-14]. Unfortunately, none of these has demonstrated consistent efficacy and some studies have even revealed loss of virologic control and the occurrence of serious adverse events (AEs) when adjunct therapies were used [10]. These findings highlight an urgent need to identify novel options as adjunct therapy for CD4+T-cell recovery and to reduce inflammation and immune activation among INRs. An ideal agent for this purpose would be well-tolerated, have few DDIs with ARVs and have a low risk of contributing to virologic failure when combined with ARVs. Based on data from the BRIGHTE study, we hypothesize that FTR would be efficacious at establishing significant immune reconstitution in INRs without compromising virologic efficacy or patient safety.

Here, we propose a self-controlled case series to evaluate the change in immunologic parameters following the addition of FTR to baseline ARV regimens among virologically suppressed INRs through 48 weeks of treatment.

Condition HIV-1-infection
Treatment Fostemsavir 600 MG [Rukobia]
Clinical Study IdentifierNCT05220358
SponsorOrlando Immunology Center
Last Modified on11 October 2022


Yes No Not Sure

Inclusion Criteria

HIV-1 infected men or women
Aged 18-65
Stable insurance plan
Documented plasma HIV-1 RNA < 50 c/mL x 2 within the last year prior to screening
Must be on a stable ARV regimen for ≥6 months prior to screening
CD4+T-cell count<350 cells/mm3 while on ARVs for at least 2 years
Must be willing to add FTR 600 mg twice daily to their current antiretroviral regimen
Must have attended ≥ 2 clinic visits in the 12 months prior to screening

Exclusion Criteria

Newly or recently diagnosed HIV-1 infection defined as HIV-1 infection diagnosed in the prior 6 months
Active HBV or HCV co-infection
Unstable liver disease or Child-Pugh C liver disease
History of autoimmune disease
History of any malignancy ≤5 years
History of radiation or cytotoxic chemotherapy
Use of systemic corticosteroids or other immunomodulatory agents in the last 14 days prior to study entry
Confirmed QT value > 500 msec at Screening or Day 1 or confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or Day 1
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note